R. Houston Thompson

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.

The safe duration of warm ischemia during partial nephrectomy remains controversial.Our aim was to evaluate the short- and long-term renal effects of warm ischemia in patients with a solitary kidney.Using the Cleveland Clinic and Mayo Clinic databases, we identified 362 patients with a solitary kidney who underwent open (n=319) or laparoscopic (n=43) partial nephrectomy using warm ischemia with hilar clamping.Associations of warm ischemia time with renal function were evaluated using logistic or Cox regression models first as a continuous variable and then in 5-min increments.Median tumor size was 3.4 cm (range: 0.7-18.0 cm), and median ischemia time was 21 min (range: 4-55 min). Postoperative acute renal failure (ARF) occurred in 70 patients (19%) including 58 (16%) who had a glomerular filtration rate (GFR) <15 ml/min per 1.73 m(2) within 30 d of surgery. Among the 226 patients with a preoperative GFR >or=30 ml/min per 1.73 m(2) and followed >or=30 d, 38 (17%) developed new-onset stage IV chronic kidney disease during follow-up. As a continuous variable, longer warm ischemia time was associated with ARF (odds ratio: 1.05 for each 1-min increase; p<0.001) and a GFR<15 (odds ratio: 1.06; p<0.001) in the postoperative period, and it was associated with new-onset stage IV chronic kidney disease (hazard ratio: 1.06; p<0.001) during follow-up. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of partial nephrectomy in a multivariable analysis. Evaluating warm ischemia in 5-min increments, a cut point of 25 min provided the best distinction between patients with and without all three of the previously mentioned end points. Limitations include the retrospective nature of the study.Longer warm ischemia time is associated with short- and long-term renal consequences. These results suggest that every minute counts when the renal hilum is clamped.

We reviewed our surgical experience with small renal tumors, comparing overall survival in patients treated with radical and partial nephrectomy.Using our nephrectomy registry we identified patients with sporadic, unilateral, solitary and localized renal masses 4 cm or less who underwent radical or partial nephrectomy between 1989 and 2003. Patients with a solitary kidney or impaired renal function at presentation were excluded, leaving 648 available for analysis. Overall survival was estimated using the Kaplan-Meier method and associations with death were evaluated using Cox proportional hazards regression.At last followup 146 patients had died of any cause and 502 were alive at a median of 7.1 years. Radical and partial nephrectomy was performed in 290 and 358 patients, respectively. In all patients radical nephrectomy was not significantly associated with death from any cause compared with partial nephrectomy (RR 1.12, p = 0.52). However, there was a significant interaction with age, leading us to stratify our analysis at the median age of 65 years. In 327 patients younger than 65 years radical nephrectomy was significantly associated with death from any cause compared with partial nephrectomy (RR 2.16, p = 0.02). The increased risk of death persisted after adjusting for year of surgery (p = 0.02), preoperative creatinine (p = 0.03), Charlson-Romano index (p = 0.04), symptoms at presentation (p = 0.02), diabetes at presentation (p = 0.03) and histology (p = 0.02).Our results suggest that, compared with partial nephrectomy, radical nephrectomy is associated with decreased overall survival in younger patients with small renal masses.

Abstract Purpose: B7-H1 is expressed by clinically aggressive forms of renal cell carcinoma (RCC) and predicts adverse outcome. B7-H1 is known to impair host immunity via interaction with the Programmed Death-1 (PD-1) receptor, which is expressed by activated T cells. Levels of immune cells expressing PD-1 (PD-1+) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1 expression is observed within aggressive RCC tumors. Experimental Design: Between 2000 and 2003, 267 patients underwent nephrectomy at our institution for clear cell RCC and had fresh-frozen tissue available for review. These RCC specimens were immunostained using anti–PD-1 (clone MIH4) and outcome analyses were conducted. Results: Mononuclear immune cell infiltration was observed in 136 (50.9%) specimens. PD-1+ immune cells were present in 77 of these 136 (56.6%) tumors. In contrast, RCC tumor cells did not express PD-1. Patients with PD-1+ immune cells were significantly more likely to harbor B7-H1+ tumor cells (P &amp;lt; 0.001), larger tumors (P = 0.001), and tumors of higher nuclear grade (P = 0.001). Likewise, intratumoral PD-1+ immune cells were associated with advanced tumor-node-metastasis stage (P = 0.005), coagulative tumor necrosis (P = 0.027), and sarcomatoid differentiation (P = 0.008). With a median follow-up of 2.9 years, 52 patients died from RCC. Univariately, patients with PD-1+ immune cells were at significant risk of cancer-specific death compared with PD-1− patients (risk ratio, 2.24; P = 0.004). Conclusions: Levels of immune cells expressing PD-1 were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC.

No AccessJournal of UrologyAdult Urology1 Apr 2010Histological Subtype is an Independent Predictor of Outcome for Patients With Renal Cell Carcinoma Bradley C. Leibovich, Christine M. Lohse, Paul L. Crispen, Stephen A. Boorjian, R. Houston Thompson, Michael L. Blute, and John C. Cheville Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Christine M. LohseChristine M. Lohse Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , Paul L. CrispenPaul L. Crispen Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Michael L. BluteMichael L. Blute Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , and John C. ChevilleJohn C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.12.035AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: There are significant differences in clinicopathological features among renal cell carcinoma histological subtypes but controversy exists regarding the independent impact of histological subtype on patient outcome after nephrectomy. We examined the significance of histological subtype on progression to distant metastasis and cancer specific death after nephrectomy. Materials and Methods: In a retrospective review of our institutional nephrectomy registry we identified 3,062 patients treated surgically for clear cell, papillary or chromophobe renal cell carcinoma between 1970 and 2003. Results: We identified 2,466 patients (80.5%) with clear cell, 438 (14.3%) with papillary and 158 (5.2%) with chromophobe renal cell carcinoma. There were significant differences in age at surgery, gender, symptoms at presentation, tumor size, stage and grade, tumor necrosis, sarcomatoid differentiation and multifocality among the 3 renal cell carcinoma subtypes (p <0.01 for all). A significant difference in metastasis-free and cancer specific survival existed between patients with clear cell renal cell carcinoma and the 2 other subtypes, although no significant difference in these outcomes was identified between patients with the papillary and chromophobe subtypes. The clear cell renal cell carcinoma subtype remained a significant predictor of metastasis (HR 2.76, 95% CI 2.05–3.73) and cancer specific death (HR 1.77, 95% CI 1.38–2.26, each p <0.001) after multivariate adjustment for the features listed above. Conclusions: Histological subtype is an independent predictor of progression to distant metastasis and cancer specific death in patients with renal cell carcinoma. References 1 : Current prognostic factors—renal cell carcinoma: Workgroup No. 4: Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer1997; 80: 994. Google Scholar 2 : Renal cell carcinoma: current prognostic factors: Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer1997; 80: 981. Google Scholar 3 : Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer—a distinct form of hereditary kidney cancer. Nat Clin Pract Urol2007; 4: 104. 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Google Scholar © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byNarayan V, Puligandla M, Haas N, Subramanian P, DiPaola R and Uzzo R (2018) Patterns of Relapse and Implications for Post-Nephrectomy Surveillance in Patients with High Risk Nonclear Cell Renal Cell Carcinoma: Subgroup Analysis of the Phase 3 ECOG-ACRIN E2805 TrialJournal of Urology, VOL. 201, NO. 1, (62-69), Online publication date: 1-Jan-2019.Capogrosso P, Larcher A, Sjoberg D, Vertosick E, Cianflone F, Dell’Oglio P, Carenzi C, Salonia A, Vickers A, Montorsi F, Bertini R and Capitanio U (2018) Risk Based Surveillance after Surgical Treatment of Renal Cell CarcinomaJournal of Urology, VOL. 200, NO. 1, (61-67), Online publication date: 1-Jul-2018.Daugherty M, Blakely S, Shapiro O, Vourganti S, Mollapour M and Bratslavsky G (2015) Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER DatabaseJournal of Urology, VOL. 195, NO. 4 Part 1, (847-851), Online publication date: 1-Apr-2016.Liu J and Gonzalgo M (2018) Editorial CommentJournal of Urology, VOL. 185, NO. 1, (35-36), Online publication date: 1-Jan-2011.Liu H, Hemminki K and Sundquist J (2018) Renal Cell Carcinoma as First and Second Primary Cancer: Etiological Clues From the Swedish Family-Cancer DatabaseJournal of Urology, VOL. 185, NO. 6, (2045-2049), Online publication date: 1-Jun-2011.Cimen H, Canda A and Balbay M (2018) Re: Outcome of Stage T2 or Greater Renal Cell Cancer Treated With Partial NephrectomyJournal of Urology, VOL. 184, NO. 5, (2212-2213), Online publication date: 1-Nov-2010. Volume 183Issue 4April 2010Page: 1309-1316 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Keywordsneoplasm metastasispathologyrenal cellcarcinomakidneymortalityMetricsAuthor Information Bradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Christine M. Lohse Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Paul L. Crispen Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Michael L. Blute Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author John C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery ( P &lt; 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence ( P &lt; 0.001 and P = 0.005) and cancer-specific death ( P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.

No AccessJournal of UrologyAdult Urology1 Jul 2012Comparative Effectiveness for Survival and Renal Function of Partial and Radical Nephrectomy for Localized Renal Tumors: A Systematic Review and Meta-Analysis Simon P. Kim, R. Houston Thompson, Stephen A. Boorjian, Christopher J. Weight, Leona C. Han, M. Hassan Murad, Nathan D. Shippee, Patricia J. Erwin, Brian A. Costello, George K. Chow, and Bradley C. Leibovich Simon P. KimSimon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota , Christopher J. WeightChristopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota , Leona C. HanLeona C. Han Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota , M. Hassan MuradM. Hassan Murad Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota , Nathan D. ShippeeNathan D. Shippee Division of Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota , Patricia J. ErwinPatricia J. Erwin Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota , Brian A. CostelloBrian A. Costello Department of Oncology, Mayo Clinic, Rochester, Minnesota , George K. ChowGeorge K. Chow Department of Urology, Mayo Clinic, Rochester, Minnesota , and Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota View All Author Informationhttps://doi.org/10.1016/j.juro.2012.03.006AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The relative effectiveness of partial vs radical nephrectomy remains unclear in light of the recent phase 3 European Organization for the Research and Treatment of Cancer trial. We performed a systematic review and meta-analysis of partial vs radical nephrectomy for localized renal tumors, considering all cause and cancer specific mortality, and severe chronic kidney disease. Materials and Methods: Cochrane Central Register of Controlled Trials, MEDLINE®, EMBASE®, Scopus and Web of Science® were searched for sporadic renal tumors that were surgically treated with partial or radical nephrectomy. Generic inverse variance with fixed effects models were used to determine the pooled HR for each outcome. Results: Data from 21, 21 and 9 studies were pooled for all cause and cancer specific mortality, and severe chronic kidney disease, respectively. Overall 31,729 (77%) and 9,281 patients (23%) underwent radical and partial nephrectomy, respectively. According to pooled estimates partial nephrectomy correlated with a 19% risk reduction in all cause mortality (HR 0.81, p <0.0001), a 29% risk reduction in cancer specific mortality (HR 0.71, p = 0.0002) and a 61% risk reduction in severe chronic kidney disease (HR 0.39, p <0.0001). However, the pooled estimate of cancer specific mortality for partial nephrectomy was limited by the lack of robustness in consistent findings on sensitivity and subgroup analyses. Conclusions: Our findings suggest that partial nephrectomy confers a survival advantage and a lower risk of severe chronic kidney disease after surgery for localized renal tumors. However, the results should be evaluated in the context of the low quality of the existing evidence and the significant heterogeneity across studies. Future research should use higher quality evidence to clearly demonstrate that partial nephrectomy confers superior survival and renal function. References 1 : Cancer statistics, 2010. 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Models for Simulation before Nephron Sparing Surgery: Methodology and Examples from a Case SeriesUrology Practice, VOL. 3, NO. 2, (124-133), Online publication date: 1-Mar-2016.Tourojman M, Kirmiz S, Boelkins B, Noyes S, Davis A, O'Donnell K, Tobert C and Lane B (2015) Impact of Reduced Glomerular Filtration Rate and Proteinuria on Overall Survival of Patients with Renal CancerJournal of Urology, VOL. 195, NO. 3, (588-593), Online publication date: 1-Mar-2016.Tabayoyong W, Abouassaly R, Kiechle J, Cherullo E, Meropol N, Shah N, Dong S, Thompson R, Smaldone M, Zhu H, Ialacci S and Kim S (2015) Variation in Surgical Margin Status by Surgical Approach among Patients Undergoing Partial Nephrectomy for Small Renal MassesJournal of Urology, VOL. 194, NO. 6, (1548-1553), Online publication date: 1-Dec-2015.Danzig M, Ghandour R, Chang P, Wagner A, Pierorazio P, Allaf M and McKiernan J (2015) Active Surveillance is Superior to Radical Nephrectomy and Equivalent to Partial Nephrectomy for 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Survival after Partial Versus Radical Nephrectomy for a Small Renal Mass: Systematic Review of Observational StudiesUrology Practice, VOL. 1, NO. 1, (27-34), Online publication date: 1-May-2014.Weight C, Miller D, Campbell S, Derweesh I, Lane B and Messing E (2013) The Management of a Clinical T1b Renal Tumor in the Presence of a Normal Contralateral KidneyJournal of Urology, VOL. 189, NO. 4, (1198-1202), Online publication date: 1-Apr-2013.Patel H, Mullins J, Pierorazio P, Jayram G, Cohen J, Matlaga B and Allaf M (2012) Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial NephrectomyJournal of Urology, VOL. 189, NO. 4, (1229-1235), Online publication date: 1-Apr-2013. Volume 188Issue 1July 2012Page: 51-57Supplementary Materials Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordskidneyrenal insufficiencymortalitycarcinoma, renal cellnephrectomyMetricsAuthor Information Simon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Christopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Leona C. Han Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota More articles by this author M. Hassan Murad Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota More articles by this author Nathan D. Shippee Division of Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota More articles by this author Patricia J. Erwin Knowledge and Evaluation Unit, Mayo Clinic, Rochester, Minnesota More articles by this author Brian A. Costello Department of Oncology, Mayo Clinic, Rochester, Minnesota More articles by this author George K. Chow Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Bradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

Partial nephrectomy (PN) is a preferred treatment for cT1 renal masses, whereas thermal ablation represents an alternative nephron-sparing option, albeit with higher reported rates of recurrence. To review our experience with PN, percutaneous radiofrequency ablation (RFA), and percutaneous cryoablation for cT1 renal masses. A total of 1803 patients with primary cT1N0M0 renal masses treated between 2000 and 2011 were identified from the prospectively maintained Mayo Clinic Renal Tumor Registry. PN compared with percutaneous ablation. Local recurrence-free, metastases-free, and overall survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. Of the 1424 cT1a patients, 1057 underwent PN, 180 underwent RFA, and 187 underwent cryoablation. In this cohort, local recurrence-free survival was similar among the three treatments (p = 0.49), whereas metastases-free survival was significantly better after PN (p = 0.005) and cryoablation (p = 0.021) when compared with RFA. Of the 379 cT1b patients, 326 patients underwent PN, and 53 patients were managed with cryoablation (8 RFA patients were excluded). In this cohort, local recurrence-free survival (p = 0.81) and metastases-free survival (p = 0.45) were similar between PN and cryoablation. In both the cT1a and cT1b groups, PN patients were significantly younger, with lower Charlson scores and had superior overall survival (p < 0.001 for all). Limitations include retrospective review and selection bias. In a large cohort of sporadic cT1 renal masses, we observed that recurrence-free survival was similar for PN and percutaneous ablation patients. Metastases-free survival was superior for PN and cryoablation patients when compared with RFA for cT1a patients. Overall survival was superior after PN, likely because of selection bias. If these results were validated, an update to clinical guidelines would be warranted. Partial nephrectomy and percutaneous ablation for small (<7-cm) and localized renal masses are associated with similar rates of local recurrence.

<h3>Objective</h3> To evaluate the effects of warm ischemia time (WIT) and quantity and quality of kidney preserved on renal functional recovery after partial nephrectomy (PN). The effect of WIT relative to these other parameters has recently been challenged. <h3>Methods</h3> We identified 362 consecutive patients with a solitary kidney who had undergone PN using warm ischemia. Multivariate models with multiple imputations were used to evaluate the associations with acute renal failure and new-onset stage IV chronic kidney disease (CKD). <h3>Results</h3> The median WIT was 21 minutes (range 4-55), the median percentage of kidney preserved was 80% (range 25%-98%), and the median preoperative glomerular filtration rate (GFR) was 61 mL/min/1.73 m² (range 11-133). Postoperative acute renal failure occurred in 70 patients (19%). Of the 226 patients with a preoperative GFR >30 mL/min/1.73 m², 38 (17%) developed new-onset stage IV CKD during follow-up. On multivariate analysis, the WIT (<i>P</i> = .021), percentage of kidney preserved (<i>P</i> = .009), and preoperative GFR (<i>P</i> < .001) were significantly associated with acute renal failure, and only the percentage of kidney preserved (<i>P</i> < .001) and preoperative GFR (<i>P</i> < .001) were significantly associated with new-onset stage IV CKD during follow-up. Using our previously published cutpoint of 25 minutes, a WIT of >25 minutes remained significantly associated with new-onset stage IV CKD in a multivariate analysis adjusting for the quantity and quality factors (hazard ratio 2.27, <i>P</i> = .049). <h3>Conclusion</h3> Our results have validated that the quality and quantity of kidney are the most important determinants of renal function after PN. In addition, we have also demonstrated that the WIT remains an important modifiable feature associated with short- and long-term renal function. The precision of surgery, maximizing the amount of preserved, vascularized parenchyma, should be a focus of study for optimizing the PN procedure.

Abstract Purpose: Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome. Experimental Design: We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome. Results: sB7-H1 was detected in the cell supernatants of some B7-H1–positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P &amp;lt; 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010). Conclusion: Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome. Clin Cancer Res; 17(7); 1915–23. ©2011 AACR.

Factors that determine renal function after partial nephrectomy are not well-defined, including the impact of cold vs warm ischemia, and the relative importance of modifiable and nonmodifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing partial nephrectomy.From 1980 to 2009, 660 partial nephrectomies were performed at 4 centers for tumor in a solitary functioning kidney under cold (300) or warm (360) ischemia. Data were collected in institutional review board approved registries and followup averaged 4.5 years. Preoperative and postoperative glomerular filtration rates were estimated via the Chronic Kidney Disease-Epidemiology Study equation.At 3 months after partial nephrectomy median glomerular filtration rate decreased by equivalent amounts with cold or warm ischemia (21% vs 22%, respectively, p = 0.7), although median cold ischemic times were much longer (45 vs 22 minutes respectively, p <0.001). On multivariable analyses increasing age, larger tumor size, lower preoperative glomerular filtration rate and longer ischemia time were associated with decreased postoperative glomerular filtration rate (p <0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative glomerular filtration rate proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance.This nonrandomized, comparative study suggests that within the relatively strict parameters of conventional practice, ie predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after partial nephrectomy. Long-term renal function after partial nephrectomy is determined primarily by the quantity and quality of renal parenchyma preserved, although type and duration of ischemia remain the most important modifiable factors, and warrant further study.

Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. To review the current evidence on the relationship of intraoperative ischemia and RF after PN. A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT <25 min, although the level of evidence to support this threshold is limited. Cold ischemia safely facilitates longer durations of ischemia. Surgical techniques that minimize or avoid global ischemia may be associated with improved RF outcomes. Although RF recovery after PN is strongly associated with quality and quantity of preserved kidney, efforts should be made to limit prolonged WIT. Cold ischemia should be preferred when longer ischemia is expected, especially in presence of imperative indications for PN. Additional research with higher levels of evidence is needed to clarify the optimal use of renal ischemia during PN. In this review of the literature, we looked at predictors of renal function after surgical resection of renal tumors. There is a strong association between the quality and quantity of renal tissue that is preserved after surgery and long-term renal function. The time of interruption of renal blood flow during surgery is an important, modifiable predictor of postoperative renal function.

B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.

The safe duration of ischemia during nephron sparing surgery remains controversial. We performed a multi-institutional study to evaluate the renal effects of vascular clamping in patients with solitary kidneys.Using the Cleveland Clinic and Mayo Clinic databases, we identified 537 patients with solitary kidneys who underwent open nephron sparing surgery. Renal complications were compared among patients who did not require vascular clamping (85), and those who had warm ischemia (174) and cold ischemia (278).Median patient age (63, 65, 64 years) and preoperative creatinine (1.4, 1.3, 1.4 mg/dl) were similar among patients with no ischemia, warm ischemia and cold ischemia, respectively. Median tumor size was smaller in patients with no ischemia (2.5 cm), compared to patients with warm (3.5 cm) and cold (4.0 cm) ischemia (p <0.001). Warm and cold ischemia was associated with a significantly increased risk of urine leak (p = 0.006), acute (p <0.001) and chronic (p = 0.027) renal failure, and temporary dialysis (p = 0.028) compared to patients with no ischemia. Warm ischemia longer than 20 minutes and cold ischemia longer than 35 minutes were associated with a higher incidence of acute renal failure (p = 0.002 and p = 0.003, respectively). Additionally, warm ischemia more than 20 minutes was associated with an increased risk of chronic renal insufficiency (41% vs 19%, p = 0.008), increase in creatinine greater than 0.5 (42% vs 15%, p <0.001) and permanent dialysis (10% vs 4%, p = 0.145).Vascular clamping during open nephron sparing surgery is associated with a higher incidence of renal complications. Attempts to limit warm ischemia to 20 minutes and cold ischemia to 35 minutes should be used when vascular clamping is necessary.

The natural history of biochemical recurrence (BCR) after radical retropubic prostatectomy (RRP) is variable and does not always translate into systemic progression or prostate cancer (PCa) death. To evaluate long-term clinical outcomes of patients with BCR and to determine predictors of disease progression and mortality in these men. We reviewed our institutional registry of 14 632 patients who underwent RRP between 1990 and 2006 to identify 2426 men with BCR (prostate-specific antigen [PSA] levels ≥0.4 ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 yr after RRP and 6.6 yr after BCR. RRP. Patients were grouped into quartiles according to time from RRP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa. Median systemic progression-free survival (PFS) and cancer-specific survival (CSS) had not been reached after 15 yr of follow-up after BCR. Cancer-specific mortality 10 yr after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 yr, 1.2–3.1 yr, 3.1–5.9 yr, and >5.9 yr after RRP, respectively (p = 0.10). On multivariate analysis, time from RRP to BCR was not significantly associated with the risk of systemic progression (p = 0.50) or cancer-specific mortality (p = 0.81). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time (DT) predicted systemic progression and death from PCa. Limitations included retrospective design, varied utilization of salvage therapies, and the inclusion of few patients with positive lymph nodes. Only a minority of men experience systemic progression and death from PCa following BCR. The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR.

Purpose To provide recommendations for the management options for patients with small renal masses (SRMs). Methods By using a literature search and prospectively defined study selection, we sought systematic reviews, meta-analyses, randomized clinical trials, prospective comparative observational studies, and retrospective studies published from 2000 through 2015. Outcomes included recurrence-free survival, disease-specific survival, and overall survival. Results Eighty-three studies, including 20 systematic reviews and 63 primary studies, met the eligibility criteria and form the evidentiary basis for the guideline recommendations. Recommendations On the basis of tumor-specific findings and competing risks of mortality, all patients with an SRM should be considered for a biopsy when the results may alter management. Active surveillance should be an initial management option for patients who have significant comorbidities and limited life expectancy. Partial nephrectomy (PN) for SRMs is the standard treatment that should be offered to all patients for whom an intervention is indicated and who possess a tumor that is amenable to this approach. Percutaneous thermal ablation should be considered an option if complete ablation can reliably be achieved. Radical nephrectomy for SRMs should only be reserved for patients who possess a tumor of significant complexity that is not amenable to PN or for whom PN may result in unacceptable morbidity even when performed at centers with expertise. Referral to a nephrologist should be considered if chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2) or progressive chronic kidney disease occurs after treatment, especially if associated with proteinuria.

While the incidence of lymph node positive prostate cancer has decreased during the prostate specific antigen era, the optimal treatment of these patients remains in question. We examined the impact of lymph node metastases on the outcome of patients following radical prostatectomy and investigated prognostic factors that affect survival.We identified 507 men treated with radical prostatectomy between 1988 and 2001 who had lymph node positive disease. Of the 507 patients 455 (89.7%) were treated with adjuvant hormonal therapy. Median followup was 10.3 years (IQR 6.1-13.5). Postoperative survival rates were estimated using the Kaplan-Meier method and the impact of various clinicopathological factors on outcome was analyzed using Cox proportional hazard regression models.Ten-year cancer specific survival for patients with positive lymph nodes was 85.8% with 56% of the men free from biochemical recurrence at last followup. On multivariate analysis pathological Gleason score 8-10 (p = 0.004), positive surgical margins (p = 0.016), nondiploid tumor ploidy (p = 0.023) and 2 or greater positive nodes (p = 0.001) were adverse predictors of cancer specific survival. Tumor stage, year of surgery and total number of nodes removed did not significantly affect outcome. Adjuvant hormonal therapy decreased the risk of biochemical recurrence (p <0.001) and local recurrence (p = 0.004) but it was not associated with systemic progression (p = 0.4) or cancer specific survival (p = 0.4).Radical prostatectomy may offer long-term survival to patients with lymph node positive prostate cancer. Gleason score, margin status, tumor ploidy and the number of involved nodes predict survival, while the role of adjuvant hormonal therapy continues to be defined.

The prognostic significance and optimal management of positive surgical margins following partial nephrectomy remain ill-defined. We combine data from 2 tertiary care intuitions, and report predictors of positive surgical margins and long-term oncological outcomes for patients with positive surgical margins.Clinical, pathological and followup data on 1,344 patients undergoing 1,390 partial nephrectomies for kidney cancer were analyzed. Patients with positive surgical margins on final pathology were treated expectantly. Univariate and multivariable logistic regression models were fit to determine clinicopathological features associated with positive surgical margins. The Kaplan-Meier method was used to estimate freedom from local disease recurrence and metastatic progression. Cox proportional hazards models were used to assess whether positive surgical margin predicted local recurrence or metastatic disease adjusting for tumor size, pathological stage, histological subtype and presence of a solitary kidney.Positive surgical margins were documented in 77 cases (5.5%). Decreasing tumor size and presence of a solitary kidney carried a significantly higher risk of positive surgical margins. The overall 10-year probability of freedom from local disease recurrence was 93% (95% CI 89, 95) and from metastatic progression 93% (95% CI 90, 95), with no significant difference between patients with positive vs negative margins (p = 0.97 and 0.18, respectively). Positive surgical margins were not associated with an increased risk of local recurrence or metastatic disease.Positive surgical margins in partial nephrectomy specimens do not uniformly portend an adverse prognosis. While every effort should be taken to ensure clear margins, our data suggest that select patients with a positive surgical margin can be safely offered vigilant monitoring without compromising long-term disease-free survival.

We evaluated our experience with renal cortical tumors to determine whether tumor size is associated with malignant histology and/or nuclear grade.We identified 2,675 patients treated surgically at our institution for renal cell carcinoma or a benign tumor between 1989 and 2007. Histological subtype and tumor size were obtained from our kidney cancer database and logistic regression analysis was performed.Of the 2,675 tumors 311 (12%) were benign and 2,364 (88%) were renal cell carcinoma. The OR for the association of malignancy with tumor size was 1.16 (95% CI 1.11-1.22, p <0.001), indicating that each 1 cm increase in tumor size was associated with a 16% increase in the odds of malignancy. The incidence of benign tumors decreased from 38% for tumors less than 1 cm to 7% for tumors 7 cm or greater. In patients with clear cell renal cell carcinoma each 1 cm increase in tumor size increased the odds of high grade disease (Fuhrman grade 3-4) compared with low grade disease (Fuhrman grade 1-2) by 25% (OR 1.25, 95% CI 1.21-1.30, p <0.001). In this subset the incidence of high grade lesions increased from 0% for tumors less than 1 cm to 59% for tumors greater than 7 cm.Our results confirm previous observations suggesting that the risks of malignancy and high grade tumors increase with tumor size. Patients with small renal masses are at low risk for harboring a high grade clear cell malignancy, which may be useful during initial consultation.

A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes.To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN).A literature review was conducted.Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration.Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications.In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes.

Telemedicine in an ambulatory surgical population remains incompletely evaluated.To investigate patient encounters in the outpatient setting using video visit (VV) technology compared to traditional office visits (OVs).From June 2013 to March 2014, 55 prescreened men with a history of prostate cancer were prospectively randomized. VVs, with the patient at home or at work, were included in the outpatient clinic calendar of urologists.Remote VV versus traditional OV.An equivalence analysis was used to assess the primary outcome, visit efficiency as measured by time studies. Secondary outcomes were patient/provider satisfaction and costs.There were 28 VVs and 27 OVs. VVs were equivalent in efficiency to relative to OVs, as measured by patient-provider face time (mean 14.5 vs 14.3min; p=0.96), patient wait time (18.4 vs 13.0min; p=0.20), and total time devoted to care (17.9 vs 17.8min; p=0.97). There were no significant differences in patient perception of visit confidentiality, efficiency, education quality, or overall satisfaction. VVs incurred lower costs, including distance traveled (median 0 vs 95 miles), travel time (0 vs 95min), missed work (0 vs 1 d), and money spent on travel ($0 vs $48; all p<0.0001). There was a high level of urologist satisfaction for both VVs (88%) and OVs (90%). The major limitation was sample size.VV in the ambulatory postprostatectomy setting may have a future role in health care delivery models. We found equivalent efficiency, similar satisfaction, but significantly reduced patient costs for VV compared to OV. Further prospective analyses are warranted.Among men with surgically treated prostate cancer, we evaluated the utility of remote video visits compared to office visits for outpatient consultation with a urologist. Video visits were associated with equivalent efficiency, similar satisfaction, and significantly lower patient costs when compared to office visits. We conclude that video visits may have a future role in health care delivery models.

Purpose To review complications related to percutaneous renal tumor ablation. Materials and Methods Prospectively collected data related to renal radiofrequency (RF) ablation and cryoablation procedures performed from May 2000 through November 2010 were reviewed. This included 573 renal ablation procedures performed in 533 patients to treat 633 tumors. A total of 254 RF ablation and 311 cryoablation procedures were performed; eight patients underwent simultaneous RF ablation and cryoablation. The mean age of patients at the time of the procedure was 70 years (range, 24–93 y), and 382 of 573 procedures (67%) were performed in male patients. Complications were recorded according to the Clavien–Dindo classification scheme. Duration of hospitalization was also documented. Results Of the 573 procedures, 63 produced complications (11.0% overall complication rate). There were 66 reported complications, of which 38 (6.6% of total procedures) were Clavien–Dindo grade II–IV major complications; there were no deaths. Major complication rates did not differ statistically (P = .15) between cryoablation (7.7%; 24 of 311) and RF ablation (4.7%; 12 of 254). Of the complications related to cryoablation, bleeding and hematuria were most common. Bleeding during cryoablation was associated with advanced age, increased tumor size, increased number of cryoprobes, and central position (P < .05). Of those treated with RF ablation, nerve and urothelial injury were most common. Mean hospitalization duration was 1 day for RF ablation and cryoablation. Conclusions Complications related to percutaneous renal ablation are infrequent. Recognition of potential complications and associated risk factors can allow optimization of periprocedural care.

While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. To evaluate the association of PBT with disease recurrence and mortality following RC. We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2–4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p < 0.0001), had a worse Eastern Cooperative Oncology Group performance status (p < 0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9–15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p < 0.001), and overall survival (45% vs 63%; p < 0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p < 0.0001) and all-cause mortality (HR: 1.05; p < 0.0001). Limitations include selection bias and lack of standardized transfusion criteria. We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.

Pretreatment neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been associated with adverse survival in a variety of malignancies. However, the relationship between NLR and oncologic outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) has not been well studied.To evaluate the association of preoperative NLR with clinicopathologic outcomes following RC.We identified 899 patients who underwent RC without neoadjuvant therapy at our institution between 1994 and 2005 and who had a pretreatment NLR.Preoperative NLR (within 90 d prior to RC) was recorded. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard and logistic regression models were used to analyze the association of NLR with clinicopathologic outcomes.Median postoperative follow-up was 10.9 yr (interquartile range: 8.3-13.9 yr). Higher preoperative NLR was associated with significantly increased risks of pathologic, extravesical tumor extension (odds ratio [OR]: 1.07; p=0.03) and lymph node involvement (OR: 1.09; p=0.02). Univariately, 10-yr cancer-specific survival was significantly worse among patients with a preoperative NLR (≥2.7 [51%] vs. <2.7 [64%]; p<0.001). Moreover, on multivariate analysis, increased preoperative NLR was independently associated with greater risks of disease recurrence (hazard ratio [HR]: 1.04; p=0.02), death from bladder cancer (HR: 1.04; p=0.01), and all-cause mortality (HR: 1.03; p=0.01).Elevated preoperative NLR among patients undergoing RC is associated with significantly increased risk for locally advanced disease as well as subsequent disease recurrence, and cancer-specific and all-cause mortality. These data suggest that serum NLR may be a useful prognostic marker for preoperative patient risk stratification, including consideration for neoadjuvant therapy and clinical trial enrollment.

Long-term data comparing partial nephrectomy (PN) and thermal ablation are lacking.To update our experience with PN, percutaneous radiofrequency ablation (RFA), and percutaneous cryoablation for cT1 renal masses.A total of 1798 patients with primary cT1N0M0 renal masses treated between 2000 and 2011 at Mayo Clinic were identified.Percutaneous ablation versus PN.Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Local recurrence, metastases, and death from renal cell carcinoma (RCC) were compared with propensity-score-adjusted Cox models.Among 1422 cT1a patients, 1055, 180, and 187 underwent PN, RFA, and cryoablation with median clinical follow-up of 9.4, 7.5, and 6.3yr, respectively. Comparisons of RFA with PN resulted in hazard ratios (HRs) of 1.49 (95% confidence interval [CI] 0.55-4.04, p=0.4), 1.46 (95% CI 0.41-5.19, p=0.6), and 1.99 (95% CI 0.29-13.56, p=0.5) for local recurrence, metastases, and death from RCC. Comparisons of cryoablation to PN resulted in HRs of 1.88 (95% CI 0.76-4.66, p=0.18), 0.23 (95% CI 0.03-1.72, p=0.15), and 0.29 (95% CI 0.01-6.11, p=0.4) for these same outcomes. Five-year CSS was 99%, 96%, and 100% for PN, RFA, and cryoablation, respectively. Among 376 cT1b patients, 324 and 52 underwent PN and cryoablation with median clinical follow-up of 8.7 and 6.0yr, respectively. Comparisons of cryoablation with PN resulted in HRs of 1.22 (95% CI 0.33-4.48, p=0.8), 0.95 (95% CI 0.21-4.38, p>0.9), and 1.94 (95% CI 0.42-8.96, p=0.4) for local recurrence, metastases, and death from RCC, respectively. Five-year CSS was 98% and 91% for PN and cryoablation, respectively. Limitations include retrospective review and selection bias.With mature follow-up at a single institution, percutaneous ablation appears to have acceptable results for cT1 renal tumors and is appropriate for patients with a contraindication for surgery. For cT1a patients, clinically relevant differences between PN and ablation are unlikely, and treatment choice should involve shared decision making. For cT1b patients, death from RCC was more common with cryoablation, and large differences in this outcome cannot be ruled out. Further research is needed to confirm the oncologic effectiveness of cryoablation in the cT1b setting.With appropriate patient triage, partial nephrectomy and percutaneous ablation can be used to treat cT1 renal masses, although additional follow-up and further study are still needed.

No AccessJournal of Urology1 Jan 2023Comparative Effectiveness for Survival and Renal Function of Partial and Radical Nephrectomy for Localized Renal Tumors: A Systematic Review and Meta-Analysis Simon P. Kim, MD, MPH M. Hassan Murad, MD, MPH R. Houston Thompson, MD Stephen A. Boorjian, MD Christopher J. Weight, MD Leona C. Han, BA Patricia J. Erwin, BA Brian A. Costello, MD George K. Chow, andMD Bradley C. LeibovichMD Simon P. KimSimon P. Kim Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , M. Hassan MuradM. Hassan Murad Mayo Clinic, Department of Preventive Medicine, Rochester, Minnesota Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Stephen A. BoorjianStephen A. Boorjian Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Christopher J. WeightChristopher J. Weight University of Minnesota, Department of Urology, Minneapolis, Minnesota More articles by this author , Leona C. HanLeona C. Han Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author , Patricia J. ErwinPatricia J. Erwin Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author , Brian A. CostelloBrian A. Costello Mayo Clinic, Department of Oncology, Rochester, Minnesota More articles by this author , George K. ChowGeorge K. Chow Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , and Bradley C. LeibovichBradley C. Leibovich Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.10.026AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited by Antonelli A, Cindolo L, Sandri M, Veccia A, Annino F, Bertagna F, Di Maida F, Celia A, D’Orta C, De Concilio B, Furlan M, Giommoni V, Ingrosso M, Mari A, Nucciotti R, Olianti C, Porreca A, Primiceri G, Schips L, Sessa F, Bove P, Simeone C and Minervini A (2023) The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trialWorld Journal of Urology, 10.1007/s00345-023-04366-3, VOL. 41, NO. 5, (1337-1344) Partezani A, Duarte-Santos H, Amaral B, Gomes Barbosa A, Apezzato M, Brunhara J, Bianco B, Lemos G and Carneiro A (2022) Outcomes of nephrectomy for renal cell carcinoma: An ecologic retrospective study in a middle-income countryArchivio Italiano di Urologia e Andrologia, 10.4081/aiua.2022.2.129, VOL. 94, NO. 2, (129-133) Vaessen C, Grobet-Jeandin E, Stolzenburg J, Arthanareeswaran V and Porter J (2022) Port Placement for Robotic Renal Surgery Robotic Urologic Surgery, 10.1007/978-3-031-00363-9_37, (447-453), . Rakul S, Romashchenko P, Pozdnyakov K and Maistrenko N (2021) Long-term results of surgical treatment for stage cT1 kidney cancerBulletin of the Russian Military Medical Academy, 10.17816/brmma75476, VOL. 23, NO. 3, (133-140) Lee C, Ryoo H, Chung J, Song W, Kang M, Sung H, Jeong B, Seo S, Jeon S, Lee H and Jeon H (2021) Preoperative versus Postoperative Compensation of the Contralateral Normal Kidney in Patients Treated with Radical Nephrectomy for Renal Cell CarcinomaJournal of Clinical Medicine, 10.3390/jcm10214918, VOL. 10, NO. 21, (4918) Guliev B (2021) Urinary fistulas after partial nephrectomy in renal cell carcinomaVestnik Urologii, 10.21886/2308-6424-2021-9-2-111-124, VOL. 9, NO. 2, (111-124) Mittakanti H, Heulitt G, Li H and Porter J (2019) Transperitoneal vs. retroperitoneal robotic partial nephrectomy: a matched-paired analysisWorld Journal of Urology, 10.1007/s00345-019-02903-7, VOL. 38, NO. 5, (1093-1099), Online publication date: 1-May-2020. Alsharm A, Bazarbashi S, Alghamdi A, Alkhateeb S, Aljubran A, Abusamra A, Alharbi H, Alotaibi M, Almansour M, Alkushi H, Ahmed I, Murshid E, Eltijani A and Rabah D (2018) Saudi oncology society and Saudi urology association combined clinical management guidelines for renal cell carcinoma 2017Urology Annals, 10.4103/UA.UA_175_17, VOL. 10, NO. 2, (123), . Tomaszewski J, Uzzo R and Chen D (2017) The Modern Basis for Nephron-Sparing Surgery in Patients with Renal Cancer Management of Urologic Cancer, 10.1002/9781118868126.ch10, (151-168) Zaid H, Parker W, Lohse C, Cheville J, Boorjian S, Leibovich B and Thompson R (2017) Patient factors associated with 30-day complications after partial nephrectomy: A contemporary updateUrologic Oncology: Seminars and Original Investigations, 10.1016/j.urolonc.2016.11.001, VOL. 35, NO. 4, (153.e1-153.e6), Online publication date: 1-Apr-2017. Banegas M, Harlan L, Mann B and Yabroff K (2016) Toward greater adoption of minimally invasive and nephron-sparing surgical techniques for renal cell cancer in the United StatesUrologic Oncology: Seminars and Original Investigations, 10.1016/j.urolonc.2016.05.021, VOL. 34, NO. 10, (433.e9-433.e17), Online publication date: 1-Oct-2016. Potretzke A and Bhayani S (2015) Laparoscopic Partial Nephrectomy: Rest in PeaceEuropean Urology, 10.1016/j.eururo.2015.01.019, VOL. 67, NO. 5, (902-903), Online publication date: 1-May-2015. Tomaszewski J, Smaldone M, Uzzo R and Kutikov A (2014) Is radical nephrectomy a legitimate therapeutic option in patients with renal masses amenable to nephron-sparing surgery?BJU International, 10.1111/bju.12696, VOL. 115, NO. 3, (357-363), Online publication date: 1-Mar-2015. Volume 0Issue 1January 2023 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Metrics Author Information Simon P. Kim Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author M. Hassan Murad Mayo Clinic, Department of Preventive Medicine, Rochester, Minnesota Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author R. Houston Thompson Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Christopher J. Weight University of Minnesota, Department of Urology, Minneapolis, Minnesota More articles by this author Leona C. Han Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author Patricia J. Erwin Mayo Clinic, Knowledge and Evaluation Research Unit, Rochester, Minnesota More articles by this author Brian A. Costello Mayo Clinic, Department of Oncology, Rochester, Minnesota More articles by this author George K. Chow Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Bradley C. Leibovich Mayo Clinic, Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract BACKGROUND Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow‐up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi‐square, Fisher exact test, and Wilcoxon rank‐sum tests. Cancer‐specific survival was estimated with the Kaplan–Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with nonnecrotic tumors was 5.27 (95% confidence interval [CI]: 4.56–6.09; P &lt; 0.001) for clear cell, 4.20 (CI: 1.65–10.68; P &lt; 0.001) for chromophobe, and 1.49 (CI: 0.81–2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P &lt; 0.001). CONCLUSIONS Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment. Cancer 2005. © 2005 American Cancer Society.

Abstract Purpose: Although the prognostic value of B7-H1 and B7-H4 expression by tumor cells in clear cell renal cell carcinoma (ccRCC) has been established, the role of B7-H3 is unknown. As such, we evaluated the association of B7-H3 expression with clinicopathologic outcomes in patients treated for ccRCC. Experimental Design: Nephrectomy specimens from 743 consecutive patients treated for ccRCC at our institution from 1990 to 1999 were evaluated for B7-H3 expression by immunohistochemical staining. Associations of B7-H3 expression with clinical and pathologic features were evaluated using χ2 and Fisher's exact tests. Associations of B7-H3 expression with death from RCC were evaluated using Cox proportional hazards regression models. Results: B7-H3 expression by tumor cells or tumor vasculature was noted in 17% and 95% of specimens, respectively. The presence of either tumor cell or diffuse tumor vasculature expression of B7-H3 was present in 46% of specimens and was associated with multiple adverse clinical and pathologic features. After multivariable adjustment, the presence of either tumor cell or diffuse tumor vasculature B7-H3 expression was significantly associated with an increased risk of death from RCC (risk ratio, 1.38; 95% confidence interval, 1.03-1.84; P = 0.029). Conclusions: Both tumor cell and tumor vasculature B7-H3 expression convey important information to predict ccRCC outcomes. Collectively, our past and present studies pertaining to B7-H ligand expression indicate that ccRCC may use redundant mechanisms to compromise host antitumoral immunity. Future studies will focus on the effect of combined B7-H ligand expression in RCC.

Abstract B7-H1 encompasses a recently discovered cell surface glycoprotein within the B7 family of T-cell coregulatory molecules. B7-H1 expression can be induced on activated T lymphocytes and is normally expressed by macrophage lineage cells. In addition, some human tumors acquire the ability to aberrantly express B7-H1. Tumor-associated B7-H1, as well as B7-H1 on activated lymphocytes, has been shown to impair antigen-specific T-cell function and survival in vitro. In contrast, in vivo monoclonal antibody–mediated blockade of B7-H1 has been shown to potentiate antitumoral responses in several murine cancer models. Consequently, tumor-associated B7-H1 has garnered much attention in the recent literature as a potential inhibitor of host antitumoral immunity. Our group has recently reported that B7-H1 is aberrantly expressed in both primary and metastatic renal cell carcinoma (RCC) as revealed via immunohistochemical staining of both fresh-frozen and paraffin-embedded nephrectomy specimens. In addition, we have shown that B7-H1 expression by clear cell RCC tumors (or infiltrating mononuclear cells) correlates with aggressive pathologic features, including advanced tumor-node-metastasis stage, tumor size, higher nuclear grade, and coagulative necrosis. In one study of 306 patients, with a median clinical follow-up of 11 years, we reported that RCC B7-H1 expression correlates with increased risk of disease progression, cancer-specific death, and overall mortality even after multivariate adjustment. Five-year cancer-specific survival rates in this study were 42% and 83% for patients harboring B7-H1+ versus B7-H1− RCC tumors, respectively. Such associations may relate to the recognized ability of B7-H1 to inhibit T-cell–mediated antitumoral immunity. In summary, B7-H1 encompasses a potent independent predictor of prognosis for patients with RCC and an extremely promising target to facilitate immunotherapeutic responses during the management of this treatment-refractory tumor.

No AccessJournal of UrologyAdult Urology1 Dec 2009Partial Versus Radical Nephrectomy for 4 to 7 cm Renal Cortical Tumorsis accompanied byIntrarenal Artery Delineation With Ultra High Resolution, Flat Panel Based, Volume Computerized Tomography: Outer Limits of Spatial Resolution R. Houston Thompson, Sameer Siddiqui, Christine M. Lohse, Bradley C. Leibovich, Paul Russo, and Michael L. Blute R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , Sameer SiddiquiSameer Siddiqui Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author , Christine M. LohseChristine M. Lohse Department of Health Sciences Research, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author , Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author , Paul RussoPaul Russo Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , and Michael L. BluteMichael L. Blute Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.08.087AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Recent observations suggest that partial nephrectomy for small renal tumors may be associated with improved survival compared with radical nephrectomy. We evaluated survival in patients with 4 to 7 cm renal tumors in a bi-institutional collaboration. Materials and Methods: By combining institutional databases from Mayo Clinic and Memorial Sloan-Kettering Cancer Center we identified 1,159 patients with 4.1 to 7.0 cm sporadic, unilateral, solitary, localized renal masses who underwent radical or partial nephrectomy between 1989 and 2006. Patient outcome was compared using Cox proportional hazards regression models. Results: Of the 1,159 patients 873 (75%) and 286 (25%) were treated with radical and partial nephrectomy, respectively. Patients treated with partial vs radical nephrectomy were significantly more likely to have a solitary kidney (10% vs 0.2%) and chronic kidney disease (15% vs 7%, each p <0.001). Median followup in survivors was 4.8 years (range 0 to 19). There was no significant difference in overall survival in patients treated with radical vs partial nephrectomy (p = 0.8). Of 943 patients with renal cell carcinoma those treated with radical nephrectomy were significantly more likely to die of renal cell carcinoma than those treated with partial nephrectomy (HR 2.16, 95% CI 1.04–4.50, p = 0.039) but this only approached statistical significance on multivariate analysis (HR 1.97, 95% CI 0.92–4.20, p = 0.079). Conclusions: Results suggest that overall and cancer specific survival is not compromised when partial nephrectomy is done for 4 to 7 cm renal cortical tumors. With the benefit of preserving renal function our results support partial nephrectomy when technically feasible for renal tumors up to 7 cm. References 1 : Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol2006; 7: 735. Google Scholar 2 : Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol2004; 171: 2181. 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Google Scholar © 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited byLaguna M (2019) Re: Clinicopathological and Survival Analysis of Clinically Advanced Papillary and Chromophobe Renal Cell CarcinomaJournal of Urology, VOL. 203, NO. 3, (460-461), Online publication date: 1-Mar-2020.Shin J, Han K, Kwon J, Kim G, Kim D, Han S, Kim H, Won J, Kim M and Lee D (2019) Clinical Results of Transarterial Embolization to Control Postoperative Vascular Complications after Partial NephrectomyJournal of Urology, VOL. 201, NO. 4, (702-708), Online publication date: 1-Apr-2019.Laguna M (2017) Re: Partial Nephrectomy versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-Analysis of Comparative StudiesJournal of Urology, VOL. 198, NO. 6, (1204-1206), Online publication date: 1-Dec-2017.Kawakami F, Rao P, Tamboli P, Wood C and Karam J (2016) Study of the Kidney Tumor-Parenchymal Interface after Neoadjuvant Treatment with Axitinib for 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Online publication date: 1-Jul-2014.Laguna M (2014) Re: Overall Survival and Development of Stage IV Chronic Kidney Disease in Patients Undergoing Partial and Radical Nephrectomy for Benign Renal TumorsJournal of Urology, VOL. 191, NO. 6, (1729-1730), Online publication date: 1-Jun-2014.Scosyrev E, Wu K, Levey H, Agrawal V, Beckham C, Wu G and Messing E (2014) Overall Survival after Partial Versus Radical Nephrectomy for a Small Renal Mass: Systematic Review of Observational StudiesUrology Practice, VOL. 1, NO. 1, (27-34), Online publication date: 1-May-2014.Poon S, Silberstein J, Chen L, Ehdaie B, Kim P and Russo P (2013) Trends in Partial and Radical Nephrectomy: An Analysis of Case Logs from Certifying UrologistsJournal of Urology, VOL. 190, NO. 2, (464-469), Online publication date: 1-Aug-2013.Patel H, Mullins J, Pierorazio P, Jayram G, Cohen J, Matlaga B and Allaf M (2012) Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial NephrectomyJournal of 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CohortJournal of Urology, VOL. 186, NO. 5, (1779-1785), Online publication date: 1-Nov-2011.Lane B, Chen H, Morrow M, Anema J and Kahnoski R (2011) Increasing Use of Kidney Sparing Approaches for Localized Renal Tumors in a Community Based Health System: Impact on Renal Functional OutcomesJournal of Urology, VOL. 186, NO. 4, (1229-1235), Online publication date: 1-Oct-2011.Weight C, Atwell T, Fazzio R, Kim S, Kenny M, Lohse C, Boorjian S, Leibovich B and Thompson R (2011) A Multidisciplinary Evaluation of Inter-Reviewer Agreement of the Nephrometry Score and the Prediction of Long-Term OutcomesJournal of Urology, VOL. 186, NO. 4, (1223-1228), Online publication date: 1-Oct-2011.Lane B, Fergany A, Weight C and Campbell S (2010) Renal Functional Outcomes After Partial Nephrectomy With Extended Ischemic Intervals are Better Than After Radical NephrectomyJournal of Urology, VOL. 184, NO. 4, (1286-1290), Online publication date: 1-Oct-2010.Related articlesJournal of Urology20 Oct 2009Intrarenal Artery Delineation With Ultra High Resolution, Flat Panel Based, Volume Computerized Tomography: Outer Limits of Spatial Resolution Volume 182Issue 6December 2009Page: 2601-2606 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsnephrectomycarcinomakidneymortalityrenal cellkidney neoplasmsAcknowledgmentsTom Manion assisted with data abstraction.MetricsAuthor Information R. Houston Thompson Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Sameer Siddiqui Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Christine M. Lohse Department of Health Sciences Research, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Bradley C. Leibovich Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Paul Russo Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Michael L. Blute Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

Recent evidence suggests significantly discordant findings regarding tumor size and the metastasis risk in renal cell carcinoma cases. We present our experience with renal cell carcinoma. We evaluated the association between tumor size and the metastasis risk in a large patient cohort.Using our prospectively maintained nephrectomy database we identified 2,691 patients who were treated surgically for a sporadic renal cortical tumor between 1989 and 2008. Associations between tumor size and synchronous metastasis at presentation (M1 renal cell carcinoma) were evaluated with logistic regression models. Metastasis-free survival after surgery was estimated using the Kaplan-Meier method in 2,367 patients who did not present with M1 renal cell carcinoma and were followed postoperatively.Of the 2,691 patients 162 presented with metastatic renal cell carcinoma. Only 1 of 781 patients with a tumor less than 3 cm had M1 renal cell carcinoma at presentation and tumor size was significantly associated with metastasis at presentation (for each 1 cm increase OR 1.25, p <0.001). Of the 2,367 patients who did not present with metastasis metastatic disease developed in 171 during a median 2.8-year followup. In this group only 1 of the 720 patients with renal cell carcinoma less than 3 cm showed de novo metastasis during followup. Metastasis-free survival was significantly associated with tumor size (for each 1 cm increase HR 1.24, p <0.001).In our experience tumor size is significantly associated with synchronous and asynchronous metastases after nephrectomy. Our results suggest that the risk of metastatic disease is negligible in patients with tumors less than 3 cm.

Expression of carbonic anhydrase IX (CAIX) has been reported to be an independent predictor of outcome and is being investigated as a therapeutic target for patients with clear cell renal cell carcinoma (ccRCC). We attempted to validate the prognostic utility of CAIX expression using a large cohort of ccRCC patients with long-term follow-up.We identified 730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999. Anti-CAIX monoclonal antibody (clone M75) was used, and tumor specimens were blindly scored for expression levels. Associations of CAIX expression with RCC death were evaluated using Cox proportional hazards regression models.There were 241 RCC deaths and a median of 9.4 years of follow-up for patients still under observation. CAIX was expressed in 708 (97.0%) of the specimens; 163 tumors (22.3%) exhibited low ( 85% tumor cells positive) expression, and 567 (77.7%) exhibited high (> 85% tumor cells positive) expression. Univariately, low CAIX expression was associated with increased risk of RCC death relative to high expression (risk ratio = 1.65; P < .001). However, low CAIX expression was not associated with RCC death after adjusting for nuclear grade or coagulative tumor necrosis. Additionally, we observed CAIX expression in a number of extrarenal organs.CAIX is strongly expressed by ccRCC. Although CAIX is associated with outcome in patients with ccRCC, it is not an independent prognostic marker. Furthermore, CAIX expression is apparent in extrarenal organs. As such, exploitation of CAIX as a prognostic marker and therapeutic target merits additional consideration.

Percutaneous Ablation of Renal Masses Measuring 3.0 cm and Smaller: Comparative Local Control and Complications After Radiofrequency Ablation and CryoablationThomas D. Atwell1, Grant D. Schmit1, Stephen A. Boorjian2, Jay Mandrekar3, A. Nicholas Kurup1, Adam J. Weisbrod1, George K. Chow2, Bradley C. Leibovich2, Matthew R. Callstrom1, David E. Patterson2, Christine M. Lohse4, and R. Houston Thompson2Audio Available | Share

Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC.Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes.Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens.Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

No AccessJournal of UrologyAdult Urology: Oncology: Adrenal/Renal/Upper Tract/Bladder1 Oct 2005IS RENAL SINUS FAT INVASION THE SAME AS PERINEPHRIC FAT INVASION FOR pT3a RENAL CELL CARCINOMA? R. HOUSTON THOMPSON, BRADLEY C. LEIBOVICH, JOHN C. CHEVILLE, W. SCOTT WEBSTER, CHRISTINE M. LOHSE, EUGENE D. KWON, IGOR FRANK, HORST ZINCKE, and MICHAEL L. BLUTE R. HOUSTON THOMPSONR. HOUSTON THOMPSON More articles by this author , BRADLEY C. LEIBOVICHBRADLEY C. LEIBOVICH More articles by this author , JOHN C. CHEVILLEJOHN C. CHEVILLE More articles by this author , W. SCOTT WEBSTERW. SCOTT WEBSTER More articles by this author , CHRISTINE M. LOHSECHRISTINE M. LOHSE More articles by this author , EUGENE D. KWONEUGENE D. KWON More articles by this author , IGOR FRANKIGOR FRANK More articles by this author , HORST ZINCKEHORST ZINCKE More articles by this author , and MICHAEL L. BLUTEMICHAEL L. BLUTE More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000173942.19990.40AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer. We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients. Materials and Methods: Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC. The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models. Results: Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC. Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09–2.46, p=0.018). In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26–2.89, p=0.002) and after adjusting for the Mayo Clinic SSIGN (stage, size, grade and necrosis) score (RR 1.90, 95% CI 1.25–2.88, p=0.003). Conclusions: Our results indicate that clear cell tumors invading the renal sinus fat are more aggressive than tumors with perinephric fat involvement. We believe both of these features should be individually assessed during routine pathological examination. External validation is needed before suggesting a change to the TNM staging system. References 1 : The process for continuous improvement of the TNM classification. Cancer2004; 100: 1. Google Scholar 2 : Update on pathologic staging of renal cell carcinoma. Urology2002; 60: 209. Google Scholar 3 : TNM T3a renal cell carcinoma: adrenal gland involvement is not the same as renal fat invasion. J Urol2003; 169: 899. Link, Google Scholar 4 : Should direct ipsilateral adrenal invasion from renal cell carcinoma be classified as pT3a?. J Urol2005; 173: 918. Link, Google Scholar 5 : Cancer specific survival for patients with pT3 renal cell carcinoma—can the 2002 primary tumor classification be improved?. J Urol2005; 173: 716. Link, Google Scholar 6 : Prognostic significance of venous thrombus in renal cell carcinoma. Are renal vein and inferior vena cava involvement different? J Urol2004; 171: 588. Google Scholar 7 : The Mayo Clinic experience with surgical management, complications and outcome for patients with renal cell carcinoma and venous tumour thrombus. BJU Int2004; 94: 33. Google Scholar 8 : Charlson co-morbidity index as a predictor of outcome after surgery for renal cell carcinoma with renal vein, vena cava or right atrium extension. J Urol2003; 169: 1282. Link, Google Scholar 9 : The renal sinus is the principal invasive pathway: a prospective study of 100 renal cell carcinomas. Am J Surg Pathol2004; 28: 1594. Google Scholar 10 : AJCC Cancer Staging Manual. New York: Springer-Verlag2002. Google Scholar 11 : Renal sinus involvement in renal cell carcinomas. Am J Surg Pathol2000; 24: 451. Google Scholar 12 : Editorial comment. J Urol2003; 169: 903. Google Scholar 13 : Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer1997; 80: 987. Crossref, Medline, Google Scholar 14 : The Heidelberg classification of renal cell tumours. J Pathol1997; 183: 131. Crossref, Medline, Google Scholar 15 : Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. Am J Clin Pathol2002; 118: 877. Google Scholar 16 : An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol2002; 168: 2395. Link, Google Scholar 17 : Original and reviewed nuclear grading according to the Fuhrman system: a multivariate analysis of 388 patients with conventional renal cell carcinoma. Cancer2005; 103: 68. Google Scholar 18 : National Wilms Tumor Study: an update for pathologists. Pediatr Dev Pathol1998; 1: 79. Google Scholar 19 : Analysis of the prognostic implications of different tumour margin types in renal cell carcinoma. Histopathology2003; 43: 374. Google Scholar From the Departments of Urology (RHT, BCL, WSW, EDK, IF, HZ, MLB) Laboratory Medicine and Pathology (JCC) and Health Sciences Research (CML) Mayo Medical School and Mayo Clinic, Rochester, Minnesota© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLaguna M (2017) Re: Urinary Collecting System Invasion is Associated with Poor Survival in Patients with Clear-Cell Renal Cell CarcinomaJournal of Urology, VOL. 198, NO. 5, (976-978), Online publication date: 1-Nov-2017.Shah P, Moreira D, Patel V, Gaunay G, George A, Alom M, Kozel Z, Yaskiv O, Hall S, Schwartz M, Vira M, Richstone L and Kavoussi L (2017) Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3aJournal of Urology, VOL. 198, NO. 2, (289-296), Online publication date: 1-Aug-2017.Laguna M (2015) Re: Evaluation of the Prognostic Significance of Perirenal Fat Invasion and Tumor Size in Patients with pT1-pT3a Localized Renal Cell Carcinoma in a Comprehensive Multicenter Study of the CORONA Project. Can we Improve Prognostic Discrimination for Patients with Stage pT3a Tumors?Journal of Urology, VOL. 194, NO. 5, (1227-1228), Online publication date: 1-Nov-2015.Chevinsky M, Imnadze M, Sankin A, Winer A, Mano R, Jakubowski C, Mashni J, Sjoberg D, Chen Y, Tickoo S, Reuter V, Hakimi A and Russo P (2015) Pathological Stage T3a Significantly Increases Disease Recurrence across All Tumor Sizes in Renal Cell CarcinomaJournal of Urology, VOL. 194, NO. 2, (310-315), Online publication date: 1-Aug-2015.Feifer A, Savage C, Rayala H, Lowrance W, Gotto G, Sprenkle P, Gupta A, Taylor J, Bernstein M, Adeniran A, Tickoo S, Reuter V and Russo P (2010) Prognostic Impact of Muscular Venous Branch Invasion in Localized Renal Cell Carcinoma CasesJournal of Urology, VOL. 185, NO. 1, (37-42), Online publication date: 1-Jan-2011.Kresowik T, Johnson M and Joudi F (2010) Combined Renal Sinus Fat and Perinephric Fat Renal Cell Carcinoma Invasion Has a Worse Prognosis Than Either AloneJournal of Urology, VOL. 184, NO. 1, (48-52), Online publication date: 1-Jul-2010.Thompson R, Siddiqui S, Lohse C, Leibovich B, Russo P and Blute M (2009) Partial Versus Radical Nephrectomy for 4 to 7 cm Renal Cortical TumorsJournal of Urology, VOL. 182, NO. 6, (2601-2606), Online publication date: 1-Dec-2009.Verhoest G, Avakian R, Bensalah K, Thuret R, Ficarra V, Artibani W, Tostain J, Guille F, Cindolo L, De La Taille A, Abbou C, Salomon L, Rioux-Leclercq N and Patard J (2009) Urinary Collecting System Invasion is an Independent Prognostic Factor of Organ Confined Renal Cell CarcinomaJournal of Urology, VOL. 182, NO. 3, (854-859), Online publication date: 1-Sep-2009.Bertini R, Roscigno M, Freschi M, Strada E, Petralia G, Pasta A, Matloob R, Sozzi F, Da Pozzo L, Colombo R, Guazzoni G, Doglioni C, Montorsi F and Rigatti P (2009) Renal Sinus Fat Invasion in pT3a Clear Cell Renal Cell Carcinoma Affects Outcomes of Patients Without Nodal Involvement or Distant MetastasesJournal of Urology, VOL. 181, NO. 5, (2027-2032), Online publication date: 1-May-2009.Nguyen M and Gill I (2009) Effect of Renal Cancer Size on the Prevalence of Metastasis at Diagnosis and MortalityJournal of Urology, VOL. 181, NO. 3, (1020-1027), Online publication date: 1-Mar-2009.Yoo C, Song C, Hong J, Kim C and Ahn H (2008) Prognostic Significance of Perinephric Fat Infiltration and Tumor Size in Renal Cell CarcinomaJournal of Urology, VOL. 180, NO. 2, (486-491), Online publication date: 1-Aug-2008.Thompson R, Cheville J, Leibovich B and Blute M (2008) Re: Location of Extrarenal Tumor Extension Does Not Impact Survival of Patients With pT3a Renal Cell CarcinomaJournal of Urology, VOL. 180, NO. 1, (409-410), Online publication date: 1-Jul-2008.Terrone C, Gontero P, Volpe A, Porpiglia F, Bollito E, Zattoni F, Frea B, Tizzani A, Fontana D, Scarpa R and Rossetti S (2008) Proposal of an Improved Prognostic Classification for pT3 Renal Cell CarcinomaJournal of Urology, VOL. 180, NO. 1, (72-78), Online publication date: 1-Jul-2008.Margulis V, Tamboli P, Matin S, Meisner M, Swanson D and Wood C (2007) Location of Extrarenal Tumor Extension Does Not Impact Survival of Patients With pT3a Renal Cell CarcinomaJournal of Urology, VOL. 178, NO. 5, (1878-1882), Online publication date: 1-Nov-2007.Ficarra V, Galfano A, Guillé F, Schips L, Tostain J, Mejean A, Lang H, Mulders P, De La Taille A, Chautard D, Descotes J, Cindolo L, Novara G, Rioux-Leclercq N, Zattoni F, Artibani W and Patard J (2007) A New Staging System for Locally Advanced (pT3–4) Renal Cell Carcinoma: A Multicenter European Study Including 2,000 PatientsJournal of Urology, VOL. 178, NO. 2, (418-424), Online publication date: 1-Aug-2007.Siddiqui S, Frank I, Leibovich B, Cheville J, Lohse C, Zincke H and Blute M (2018) Impact of Tumor Size on the Predictive Ability of the pT3a Primary Tumor Classification for Renal Cell CarcinomaJournal of Urology, VOL. 177, NO. 1, (59-62), Online publication date: 1-Jan-2007. Volume 174Issue 4 Part 1October 2005Page: 1218-1221 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordscarcinoma, renal cellneoplasm staging, kidney neoplasms, prognosisMetricsAuthor Information R. HOUSTON THOMPSON More articles by this author BRADLEY C. LEIBOVICH More articles by this author JOHN C. CHEVILLE More articles by this author W. SCOTT WEBSTER More articles by this author CHRISTINE M. LOHSE More articles by this author EUGENE D. KWON More articles by this author IGOR FRANK More articles by this author HORST ZINCKE More articles by this author MICHAEL L. BLUTE More articles by this author Expand All Advertisement PDF downloadLoading ...

The safe duration of warm ischemia during partial nephrectomy (PN) remains controversial. To compare the short- and long-term renal effects of warm ischemia versus no ischemia in patients with a solitary kidney. Using the Cleveland Clinic and Mayo Clinic databases, we identified 458 patients who underwent open (n = 411) or laparoscopic (n = 47) PN for a renal mass in a solitary kidney between 1990 and 2008. Patients treated with cold ischemia were excluded. Associations of ischemia type (none vs warm) with short- and long-term renal function were evaluated using logistic or Cox regression models. No ischemia was used in 96 patients (21%), while 362 patients (79%) had a median of 21 min (range: 4–55) of warm ischemia. Patients treated with warm ischemia had a significantly higher preoperative glomerular filtration rate (GFR; median: 61 ml/min per 1.73 m2 vs 54 ml/min per 1.73 m2; p < 0.001) and larger tumors (median: 3.4 cm vs 2.5 cm; p < 0.001) compared with patients treated with no ischemia. Warm ischemia patients were significantly more likely to develop acute renal failure (odds ratio [OR]: 2.1; p = 0.044) and a GFR <15 ml/min per 1.73 m2 in the postoperative period (OR: 4.2; p = 0.007) compared with patients who did not have hilar clamping. Among the 297 patients with a preoperative GFR ≥30 ml/min per 1.73 m2, patients with warm ischemia were significantly more likely to develop new-onset stage IV chronic kidney disease (hazard ratio: 2.3; p = 0.028) during a mean follow-up of 3.3 yr. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of PN in a multivariable analysis. Limitations include surgeon selection bias when determining type of ischemia. Warm ischemia during PN is associated with adverse renal consequences. Although selection bias is present, PN without ischemia should be used when technically feasible in patients with a solitary kidney.

No AccessJournal of UrologyAdult Urology1 Mar 2009Contemporary Use of Partial Nephrectomy at a Tertiary Care Center in the United States R. Houston Thompson, Matt Kaag, Andrew Vickers, Shilajit Kundu, Melanie Bernstein, William Lowrance, David Galvin, Guido Dalbagni, Karim Touijer, and Paul Russo R. Houston ThompsonR. Houston Thompson More articles by this author , Matt KaagMatt Kaag More articles by this author , Andrew VickersAndrew Vickers More articles by this author , Shilajit KunduShilajit Kundu More articles by this author , Melanie BernsteinMelanie Bernstein More articles by this author , William LowranceWilliam Lowrance More articles by this author , David GalvinDavid Galvin More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Karim TouijerKarim Touijer More articles by this author , and Paul RussoPaul Russo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.11.017AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The use of partial nephrectomy for renal cortical tumors appears unacceptably low in the United States according to population based data. We examined the use of partial nephrectomy at our tertiary care facility in the contemporary era. Materials and Methods: Using our prospectively maintained nephrectomy database we identified 1,533 patients who were treated for a sporadic and localized renal cortical tumor between 2000 and 2007. Patients with bilateral disease or solitary kidneys were excluded from study and elective operation required an estimated glomerular filtration rate of 45 ml per minute per 1.73 m2 or greater. Predictors of partial nephrectomy were evaluated using logistic regression models. Results: Overall 854 (56%) and 679 patients (44%) were treated with partial and radical nephrectomy, respectively. In the 820 patients treated electively for a tumor 4 cm or less the frequency of partial nephrectomy steadily increased from 69% in 2000 to 89% in 2007. In the 365 patients treated electively for a 4 to 7 cm tumor the frequency of partial nephrectomy also steadily increased from 20% in 2000 to 60% in 2007. On multivariate analysis male gender (p = 0.025), later surgery year (p <0.001), younger patient age (p = 0.005), smaller tumor (p <0.001) and open surgery (p <0.001) were significant predictors of partial nephrectomy. American Society of Anesthesiologists score, race and body mass index were not significantly associated with treatment type. Conclusions: The use of partial nephrectomy is increasing and it is now performed in approximately 90% of patients with T1a tumors at our institution. For reasons that remain unclear certain groups of patients are less likely to be treated with partial nephrectomy. References 1 : Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol2006; 7: 735. Google Scholar 2 : Complications of contemporary open nephron sparing surgery: a single institution experience. J Urol2005; 174: 855. Link, Google Scholar 3 : Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol2004; 171: 2181. Link, Google Scholar 4 : Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol2006; 49: 308. Google Scholar 5 : Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc2000; 75: 1236. Crossref, Medline, Google Scholar 6 : Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol2008; 179: 468. Link, Google Scholar 7 : Renal and cardiovascular morbidity after partial or radical nephrectomy. Cancer2008; 112: 511. Google Scholar 8 : Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol2004; 171: 1066. Link, Google Scholar 9 : Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm. BJU Int2006; 97: 939. Google Scholar 10 : Partial nephrectomy for small renal masses: an emerging quality of care concern?. J Urol2006; 175: 853. Link, Google Scholar 11 : National utilization trends of partial nephrectomy for renal cell carcinoma: a case of underutilization?. Urology2006; 67: 254. Google Scholar 12 : A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation: Modification of Diet in Renal Disease Study Group. Ann Intern Med1999; 130: 461. Google Scholar 13 : Treatment of renal cell carcinoma by in situ partial nephrectomy and extracorporeal operation with autotransplantation. Mayo Clin Proc1985; 60: 651. Crossref, Medline, Google Scholar 14 : Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. J Urol1989; 141: 835. Link, Google Scholar 15 : Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med2004; 351: 1296. Google Scholar 16 : Complications of radical and partial nephrectomy in a large contemporary cohort. J Urol2004; 171: 130. Link, Google Scholar 17 : Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol2003; 170: 64. Link, Google Scholar 18 : Comparison between open partial and radical nephrectomy for renal tumours: perioperative outcome and health-related quality of life. Eur Urol2007; 51: 614. Google Scholar 19 : Comparison of direct hospital costs and length of stay for radical nephrectomy versus nephron-sparing surgery in the management of localized renal cell carcinoma. Urology1999; 54: 994. Google Scholar 20 : A comparison of hospital-based charges following partial and radical nephrectomy. Urol Oncol2002; 7: 3. Google Scholar 21 : 5-Year outcomes of laparoscopic partial nephrectomy. J Urol2007; 177: 70. Link, Google Scholar Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York© 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited byLaguna M (2016) Re: Partial vs Radical Nephrectomy for T1 Renal Tumours: An Analysis from the British Association of Urological Surgeons Nephrectomy AuditJournal of Urology, VOL. 195, NO. 5, (1377-1379), Online publication date: 1-May-2016.Lane B, Golan S, Eggener S, Tobert C, Kahnoski R, Kutikov A, Smaldone M, Whelan C, Shalhav A and Uzzo R (2013) Differential Use of Partial Nephrectomy for Intermediate and High Complexity Tumors May Explain Variability in Reported Utilization RatesJournal of Urology, VOL. 189, NO. 6, (2047-2053), Online publication date: 1-Jun-2013.Tanagho Y, Figenshau R, Sandhu G and Bhayani S (2012) Is There a Financial Disincentive to Perform Partial Nephrectomy?Journal of Urology, VOL. 187, NO. 6, (1995-1999), Online publication date: 1-Jun-2012.Kim S, Shah N, Weight C, Thompson R, Moriarty J, Shippee N, Costello B, Boorjian S and Leibovich B (2011) Contemporary Trends in Nephrectomy for Renal Cell Carcinoma in the United States: Results From a Population Based CohortJournal of Urology, VOL. 186, NO. 5, (1779-1785), Online publication date: 1-Nov-2011.Lane B, Chen H, Morrow M, Anema J and Kahnoski R (2011) Increasing Use of Kidney Sparing Approaches for Localized Renal Tumors in a Community Based Health System: Impact on Renal Functional OutcomesJournal of Urology, VOL. 186, NO. 4, (1229-1235), Online publication date: 1-Oct-2011.Godoy G, Katz D, Adamy A, Jamal J, Bernstein M and Russo P (2011) Routine Drain Placement After Partial Nephrectomy is Not Always NecessaryJournal of Urology, VOL. 186, NO. 2, (411-416), Online publication date: 1-Aug-2011.Cooperberg M, Mallin K, Kane C and Carroll P (2011) Treatment Trends for Stage I Renal Cell CarcinomaJournal of Urology, VOL. 186, NO. 2, (394-399), Online publication date: 1-Aug-2011.Lane B (2011) What is the Best Method of Preoperatively Determining the Management of Small Renal Masses?Journal of Urology, VOL. 186, NO. 1, (12-13), Online publication date: 1-Jul-2011.Ghoneim T, Thornton R, Solomon S, Adamy A, Favaretto R and Russo P (2011) Selective Arterial Embolization for Pseudoaneurysms and Arteriovenous Fistula of Renal Artery Branches Following Partial NephrectomyJournal of Urology, VOL. 185, NO. 6, (2061-2065), Online publication date: 1-Jun-2011.Lane B, Fergany A, Weight C and Campbell S (2010) Renal Functional Outcomes After Partial Nephrectomy With Extended Ischemic Intervals are Better Than After Radical NephrectomyJournal of Urology, VOL. 184, NO. 4, (1286-1290), Online publication date: 1-Oct-2010.Lowrance W, Yee D, Savage C, Cronin A, O'Brien M, Donat S, Vickers A and Russo P (2010) Complications After Radical and Partial Nephrectomy as a Function of AgeJournal of Urology, VOL. 183, NO. 5, (1725-1730), Online publication date: 1-May-2010.Weight C, Larson B, Fergany A, Gao T, Lane B, Campbell S, Kaouk J, Klein E and Novick A (2010) Nephrectomy Induced Chronic Renal Insufficiency is Associated With Increased Risk of Cardiovascular Death and Death From Any Cause in Patients With Localized cT1b Renal MassesJournal of Urology, VOL. 183, NO. 4, (1317-1323), Online publication date: 1-Apr-2010. Volume 181Issue 3March 2009Page: 993-997 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordskidney neoplasmscarcinomanephrectomymortalityrenal cellkidneyMetricsAuthor Information R. Houston Thompson More articles by this author Matt Kaag More articles by this author Andrew Vickers More articles by this author Shilajit Kundu More articles by this author Melanie Bernstein More articles by this author William Lowrance More articles by this author David Galvin More articles by this author Guido Dalbagni More articles by this author Karim Touijer More articles by this author Paul Russo More articles by this author Expand All Advertisement PDF downloadLoading ...

Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings.The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry.B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06).B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.

Predicting oncologic outcomes is important for patient counseling, clinical trial design, and biomarker study testing. To develop prognostic models for progression-free (PFS) and cancer-specific survival (CSS) in patients with clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chrRCC). Retrospective cohort review of the Mayo Clinic Nephrectomy registry from 1980 to 2010, for patients with nonmetastatic ccRCC, papRCC, and chrRCC. Partial or radical nephrectomy. PFS and CSS from date of surgery. Multivariable Cox proportional hazards regression was used to develop parsimonious models based on clinicopathologic features to predict oncologic outcomes and were evaluated with c-indexes. Models were converted into risk scores/groupings and used to predict PFS and CSS rates after accounting for competing risks. A total of 3633 patients were identified, of whom 2726 (75%) had ccRCC, 607 (17%) had papRCC, and 222 (6%) had chrRCC. Models were generated for each histologic subtype and a risk score/grouping was developed for each subtype and outcome (PFS/CSS). For PFS, the c-indexes were 0.83, 0.77, and 0.78 for ccRCC, papRCC, and chrRCC, respectively. For CSS, c-indexes were 0.86 and 0.83 for ccRCC and papRCC. Due to only 22 deaths from RCC, we did not assess a multivariable model for chrRCC. Limitations include the single institution study, lack of external validation, and its retrospective nature. Using a large institutional experience, we generated specific prognostic models for oncologic outcomes in ccRCC, papRCC, and chrRCC that rely on features previously shown—and validated—to be associated with survival. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment. We identified routinely available clinical and pathologic features that can accurately predict progression and death from renal cell carcinoma following surgery. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment.

Chromosomal rearrangements involving the anaplastic lymphoma kinase gene (ALK) at 2p23 result in fusion with various partner genes leading to aberrant production of oncogenic protein products in multiple tumor types. Recently, the ALK protein inhibitor crizotinib was shown to be an effective therapy in patients with ALK-rearranged non-small cell lung cancer. The goal of this study was to determine the frequency of ALK alterations in adult renal cell carcinoma (RCC) and define associated clinicopathologic features and outcome. RCCs from a cohort of 534 consecutive surgically treated adult patients were analyzed for alterations of ALK by fluorescence in situ hybridization. ALK rearrangements were identified in 2 of 534 (<1%) RCCs. Both showed similar histologic features and the patients had a poor outcome. ALK copy number gain was identified in 54 (10%) RCCs. In clear cell type RCC (CCRCC), ALK copy number gain was significantly associated with tumor size (P=0.02) and nuclear grade (P<0.001), and with a worse 10-year cancer-specific survival vs similar patients lacking ALK copy number gain (P=0.03). ALK rearrangement is rare in adult RCC but may be associated with distinct histological features and poor outcome. Another potential mechanism to elevate ALK expression, increased ALK gene copy number, was observed in 10% of adult CCRCC, where it is associated with a higher tumor grade and poorer outcome. Additional studies are necessary to determine whether patients RCCs with ALK rearrangement and/or those with an increase in ALK copy number would benefit from ALK inhibitor treatment.

Purpose The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide guidelines for surveillance after surgery for renal cell carcinoma (RCC). Herein, we assess the ability of the guidelines to capture RCC recurrences and determine the duration of surveillance required to capture 90%, 95%, and 100% of recurrences. Patients and Methods We evaluated 3,651 patients who underwent surgery for M0 RCC between 1970 and 2008. Patients were stratified as AUA low risk (pT1Nx-0) after partial (LR-partial) or radical nephrectomy (LR-radical) or as moderate/high risk (M/HR; pT2-4Nx-0/pTanyN1). Guidelines were assessed by calculating the percentage of recurrences detected when following the 2013 and 2014 NCCN and AUA recommendations, and associated Medicare costs were compared. Results At a median follow-up of 9.0 years (interquartile range, 5.7 to 14.4 years), a total of 1,088 patients (29.8%) experienced a recurrence. Of these, 390 recurrences (35.9%) were detected using 2013 NCCN recommendations, 742 recurrences (68.2%) were detected using 2014 NCCN recommendations, and 728 recurrences (66.9%) were detected using AUA recommendations. All protocols missed the greatest amount of recurrences in the abdomen and among pT1Nx-0 patients. To capture 95% of recurrences, surveillance was required for 15 years for LR-partial, 21 years for LR-radical, and 14 years for M/HR patients. Medicare surveillance costs for one LR-partial patient were $1,228.79 using 2013 NCCN, $2,131.52 using 2014 NCCN, and $1,738.31 using AUA guidelines. However, if 95% of LR-partial recurrences were captured, costs would total $9,856.82. Conclusion If strictly followed, the 2014 NCCN and AUA guidelines will miss approximately one third of RCC recurrences. Improved surveillance algorithms, which balance patient benefits and health care costs, are needed.

Renal cell carcinoma (RCC) with chromosomal rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) at Xp11.2 is a distinct subtype that was initially described in children and has been reported to display an indolent course. Recent reports have identified RCC with TFE3 rearrangements in adults and have suggested a more aggressive course in this population. However, only a few studies have examined these tumors in a large series of consecutively treated adults. We screened 632 RCCs from patients consecutively treated by surgery at a single institution by fluorescence in situ hybridization to detect TFE3 rearrangements. We identified 6 RCCs with TFE3 rearrangement. Patient ages ranged from 25 to 78 years and included 4 women and 2 men. Tumors showed significant histologic variability. Comparison of the clinical and pathologic features between RCCs with TFE3 rearrangements and RCCs without TFE3 rearrangements showed no significant differences. Follow-up period for patients with TFE3-rearranged RCC ranged from 0.8 to 16.5 years, with 4 of 6 dying from the disease. Cancer-specific survival for patients with TFE3-rearranged RCC was significantly worse than for patients with TFE3-rearrangement-negative papillary-type RCC (P<0.001) but not different from that for TFE3-rearrangement-negative clear cell-type RCC. In conclusion, we present an assessment of TFE3 rearrangement status in a large series of adults consecutively treated by surgery for RCC. Our findings confirm that RCCs with TFE3 rearrangement account for only approximately 1% of adult RCCs. The results also suggest that adult RCC with TFE3 rearrangement may be a clinically aggressive tumor.

No AccessJournal of UrologyAdult Urology1 Jan 2013Usefulness of R.E.N.A.L. Nephrometry Scoring System for Predicting Outcomes and Complications of Percutaneous Ablation of 751 Renal Tumors Grant D. Schmit, R. Houston Thompson, Anil N. Kurup, Adam J. Weisbrod, Stephen A. Boorjian, Rickey E. Carter, Jennifer R. Geske, Matthew R. Callstrom, and Thomas D. Atwell Grant D. SchmitGrant D. Schmit Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Anil N. KurupAnil N. Kurup Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Adam J. WeisbrodAdam J. Weisbrod Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Rickey E. CarterRickey E. Carter Department of Biostatistics, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Jennifer R. GeskeJennifer R. Geske Department of Biostatistics, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author , Matthew R. CallstromMatthew R. Callstrom Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota Financial interest and/or other relationship with Endocure and Siemens Medical. More articles by this author , and Thomas D. AtwellThomas D. Atwell Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.08.180AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We applied the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry scoring system to renal tumors treated with percutaneous ablation to determine whether this score is associated with oncological outcomes and complications. Materials and Methods: A total of 751 renal tumors were treated at 679 percutaneous ablation sessions in 627 patients at our institution between 2000 and 2012. Of these renal masses 430 (57%) were treated with cryoablation and the remaining 321 were treated with radio frequency ablation. R.E.N.A.L. tumor scores were analyzed to determine the association of the score with ablation treatment outcomes and complications according to Clavien criteria. Results: The mean ± SD R.E.N.A.L. nephrometry score of all ablated tumors was 6.7 ± 1.9. Those treated with cryoablation had higher scores than those treated with radio frequency ablation (mean 7.2 ± 1.9 vs 6.1 ± 1.8, p <0.001). We identified a total of 28 local treatment failures (3.7%) in the 751 tumors during a mean computerized tomography/magnetic resonance imaging followup of 27.9 ± 27.8 months. There was a significant association between R.E.N.A.L. nephrometry score and local treatment failure. Mean nephrometry score was 7.6 ± 2.2 vs 6.7 ± 1.9 for tumors with vs without local treatment failure (p <0.001). Of the 679 ablation treatments 38 (5.6%) major (grade 3 or greater) patient complications occurred. There was a significant association between R.E.N.A.L. nephrometry score and major complications. Patients with vs without a major complication had a mean nephrometry score of 8.1 ± 2.0 vs 6.8 ± 1.9 (p <0.001). Conclusions: The R.E.N.A.L. nephrometry scoring system predicts treatment efficacy and complications following percutaneous renal ablation. References 1 : Outcomes following partial nephrectomy by tumor size. J Urol2008; 180: 1912. Link, Google Scholar 2 : The changing natural history of renal cell carcinoma. J Urol2001; 166: 1611. Link, Google Scholar 3 : Solid renal tumors: an analysis of pathological features related to tumor size. J Urol2003; 170: 2217. Link, Google Scholar 4 : Imaging-guided radiofrequency ablation of solid renal tumors. AJR Am J Roentgenol2003; 180: 1509. Google Scholar 5 : Radiofrequency ablation of renal cell carcinoma: Part 1. Indications, results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol2005; 185: 64. 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Link, Google Scholar 13 : Preoperative aspects and dimensions used for anatomical (PADUA) classification of renal tumors in patients who are candidates for nephron-sparing surgery. Eur Urol2009; 56: 786. Google Scholar 14 : Kidney tumor location measurement using the C index method. J Urol2010; 183: 1708. Link, Google Scholar 15 : Utility of the R.E.N.A.L. nephrometry scoring system in objectifying treatment decision-making of the enhancing renal mass. Urology2011; 78: 1089. Google Scholar 16 : Utility of the RENAL nephrometry scoring system in the real world: predicting surgeon operative preference and complication risk. BJU Int2012; 109: 700. Google Scholar 17 : Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL nephrometry score. Eur Urol2011; 60: 241. Google Scholar 18 : Does nephrometry scoring of renal tumors predict outcomes in patients selected for robotic-assisted partial nephrectomy?. J Endourol2011; 25: 1649. Google Scholar 19 : Renal nephrometry score is associated with urine leak after partial nephrectomy. BJU Int2010; 108: 67. Google Scholar 20 : Objective measures of renal mass anatomic complexity predict rates of major complications following partial nephrectomy. Eur Urol2011; 60: 724. Google Scholar 21 : Thermal ablation of the small renal mass: case selection using the R.E.N.A.L.-nephrometry score. Urol OncolApril 20, 2012; . Epub ahead of print. Google Scholar 22 : Percutaneous cryoablation of renal masses ≥ 3cm: efficacy and safety in treatment of 108 patients. J Endourology2010; 24: 1255. Google Scholar 23 : Image-guided tumor ablation: standardization of terminology and reporting criteria. Radiology2005; 235: 728. Google Scholar 24 : Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg2004; 240: 205. Google Scholar 25 : Assessing kidney function: measured and estimated glomerular filtration rate. N Engl J Med2006; 354: 2473. Google Scholar 26 : Paranephric water instillation: a technique to prevent bowel injury during percutaneous renal radiofrequency ablation. AJR Am J Roentgenol2003; 181: 1315. Google Scholar 27 : Hydrodisplacement in the percutaneous cryoablation of 50 renal tumors. AJR Am J Roentgenol2010; 194: 779. Google Scholar 28 : Protecting the ureter during radiofrequency ablation of renal cell cancer: a pilot study of retrograde pyeloperfusion with cooled dextrose 5% in water. J Vasc Interv Radiol2008; 19: 1034. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByLaguna M (2018) Re: Mortality, Morbidity and Healthcare Expenditures after Local Tumour Ablation or Partial Nephrectomy for T1A Kidney CancerJournal of Urology, VOL. 198, NO. 2, (252-254), Online publication date: 1-Aug-2017.Cadeddu J (2018) Re: Percutaneous Cryoablation of Stage T1b Renal Cell Carcinoma: Technique Considerations, Safety, and Local Tumor ControlJournal of Urology, VOL. 195, NO. 1, (62-63), Online publication date: 1-Jan-2016.Sabir S, Ahrar K and Matin S (2018) Predicting and Determining the Success of Percutaneous AblationJournal of Urology, VOL. 196, NO. 1, (7-8), Online publication date: 1-Jul-2016.Laguna M (2018) Re: Prediction of Complications following Partial Nephrectomy: Implications for Ablative Techniques CandidatesJournal of Urology, VOL. 196, NO. 3, (685-687), Online publication date: 1-Sep-2016.Chang X, Liu T, Zhang F, Qian C, Ji C, Zhao X, Liu G and Guo H (2018) The Comparison of R.E.N.A.L., PADUA and Centrality Index Score in Predicting Perioperative Outcomes and Complications after Laparoscopic Radio Frequency Ablation of Renal TumorsJournal of Urology, VOL. 194, NO. 4, (897-902), Online publication date: 1-Oct-2015.Laguna M (2018) Re: Long-Term Oncologic Outcomes after Radiofrequency Ablation for T1 Renal Cell CarcinomaJournal of Urology, VOL. 190, NO. 4, (1205-1206), Online publication date: 1-Oct-2013. Volume 189Issue 1January 2013Page: 30-35 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordscryosurgeryforecastingcatheter ablationcarcinoma, renal cellkidneyMetricsAuthor Information Grant D. Schmit Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Anil N. Kurup Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Adam J. Weisbrod Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Rickey E. Carter Department of Biostatistics, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Jennifer R. Geske Department of Biostatistics, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Matthew R. Callstrom Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota Financial interest and/or other relationship with Endocure and Siemens Medical. More articles by this author Thomas D. Atwell Department of Radiology, Mayo Clinic School of Medicine, Rochester, Minnesota More articles by this author Expand All Advertisement PDF DownloadLoading ...

No AccessJournal of UrologyAdult Urology1 Aug 2012The Impact of Squamous and Glandular Differentiation on Survival After Radical Cystectomy for Urothelial Carcinoma Simon P. Kim, Igor Frank, John C. Cheville, R. Houston Thompson, Christopher J. Weight, Prabin Thapa, and Stephen A. Boorjian Simon P. KimSimon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Igor FrankIgor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , John C. ChevilleJohn C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Christopher J. WeightChristopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Prabin ThapaPrabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , and Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.04.020AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We investigated the clinicopathological outcomes of patients treated with cystectomy for pure urothelial carcinoma vs urothelial carcinoma, and squamous and/or glandular differentiation. Materials and Methods: We reviewed the records of 1,013 patients who underwent radical cystectomy, including 827 (72%) with pure urothelial carcinoma and 186 (18%) with urothelial carcinoma, and squamous and/or glandular differentiation. Of patients with variant histology 132 had squamous differentiation, 41 had glandular features and 13 had each type. Cancer specific survival was estimated using the Kaplan-Meier method. The association of histological differentiation with death from bladder cancer was evaluated using multivariate Cox proportional hazard regression analysis. Results: Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have pT3-T4 tumors (70% vs 38%, p <0.0001) and pN+ disease (20% vs 15%, p = 0.05) than those with pure urothelial carcinoma. Median followup was 11.4 years. A total of 432 patients died of bladder cancer, including 77 with histological differentiation and 355 with pure urothelial carcinoma. Ten-year cancer specific survival did not significantly differ between patients with urothelial carcinoma and histological differentiation, and those with pure urothelial carcinoma (52% vs 51%, p = 0.71). After adjusting for clinicopathological features squamous and/or glandular differentiation was not significantly associated with the risk of death from bladder cancer (HR 0.79, p = 0.10). Conclusions: Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have extravesical tumors and node positive disease. Nevertheless, they did not have adverse survival compared to patients with pure urothelial carcinoma. Additional studies are needed to further define prognostic factors in such patients. References 1 : Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum Pathol2006; 37: 1371. Google Scholar 2 : Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection. Urology2007; 70: 69. 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Google Scholar 24 : Adenocarcinoma versus urothelial carcinoma of the urinary bladder: comparison between pathologic stage at radical cystectomy and cancer-specific mortality. Urology2010; 75: 376. Google Scholar 25 : Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions. Cancer Res1999; 59: 3003. Google Scholar 26 : Molecular evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma. Am J Pathol2005; 166: 1533. Google Scholar 27 : Histogenesis of nonurothelial carcinomas of the urinary bladder from pre-existent transitional cell carcinomas: A histopathological and immunohistochemical study. Urol Res2002; 30: 66. Google Scholar 28 : Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation. Am J Clin Pathol2003; 120: 93. Google Scholar 29 : Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma. Histopathology2011; 59: 710. Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byHajiran A, Azizi M, Aydin A, Zemp L, Peyton C, Dhillon J, Nealon S, Reich R, Cao B, Li R, Manley B, Sexton W and Gilbert S (2020) Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant ChemotherapyJournal of Urology, VOL. 205, NO. 1, (100-108), Online publication date: 1-Jan-2021.Mori K, Abufaraj M, Mostafaei H, Quhal F, Karakiewicz P, Briganti A, Kimura S, Egawa S and Shariat S (2020) A Systematic Review and Meta-Analysis of Variant Histology in Urothelial Carcinoma of the Bladder Treated with Radical CystectomyJournal of Urology, VOL. 204, NO. 6, (1129-1140), Online publication date: 1-Dec-2020.Yang D, Monn M, Kaimakliotis H, Cho J, Cary K, Pedrosa J, Bihrle R, Cheng L and Koch M (2015) Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?Urology Practice, VOL. 2, NO. 6, (335-342), Online publication date: 1-Nov-2015.Linder B, Boorjian S, Cheville J, Sukov W, Thapa P, Tarrell R and Frank I (2013) The Impact of Histological Reclassification during Pathology Re-Review—Evidence of a Will Rogers Effect in Bladder Cancer?Journal of Urology, VOL. 190, NO. 5, (1692-1697), Online publication date: 1-Nov-2013. Volume 188Issue 2August 2012Page: 405-409 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordshistologyurotheliumcarcinomaurinary bladder neoplasmsmortalityMetrics Author Information Simon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Igor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author John C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Christopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Prabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

No AccessJournal of UrologyAdult Urology1 Jul 2013Comparative Performance of Comorbidity Indices for Estimating Perioperative and 5-Year All Cause Mortality Following Radical Cystectomy for Bladder Cancer Stephen A. Boorjian, Simon P. Kim, Matthew K. Tollefson, Alonso Carrasco, John C. Cheville, R. Houston Thompson, Prabin Thapa, and Igor Frank Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Novartis and Endo Pharmaceuticals. More articles by this author , Simon P. KimSimon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , Matthew K. TollefsonMatthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , Alonso CarrascoAlonso Carrasco Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , John C. ChevilleJohn C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , Prabin ThapaPrabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author , and Igor FrankIgor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Rochester Medical Company. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.01.010AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Radical cystectomy continues to be associated with a nonnegligible risk of perioperative death and all cause mortality in the years after surgery remains relatively high. We investigated the comparative ability of various comorbidity indices to predict perioperative and 5-year all cause mortality after radical cystectomy. Materials and Methods: We evaluated 891 patients who underwent radical cystectomy between 1994 and 2005. The associations of American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, Elixhauser index and ECOG (Eastern Cooperative Oncology Group) performance status with outcomes were assessed using Cox regression models. Model performance was compared with area under receiver operating curves. Results: A total of 33 (3.7%) patients died within 90 days of radical cystectomy. On multivariate analysis locally advanced pathological tumor stage (HR 4.86, p = 0.002) as well as Elixhauser index (HR 1.48, p = 0.002), ASA score (HR 3.17, p = 0.001) and ECOG (HR 2.40, p <0.0001) were significantly associated with 90-day perioperative mortality. Median followup after radical cystectomy was 10.1 years, during which time 576 patients died. Charlson comorbidity index (HR 1.23, p <0.0001), Elixhauser index (HR 1.28, p <0.0001), ASA score (HR 1.44, p = 0.007) and ECOG (HR 1.97, p <0.0001) were independent predictors of 5-year all cause mortality. Moreover Charlson comorbidity index (AUC 0.798, p <0.0001), Elixhauser index (AUC 0.770, p = 0.03) and ECOG (AUC 0.769, p = 0.03) significantly enhanced the performance of a base model which did not include comorbidity status (AUC 0.757) to predict 5-year all cause mortality. Conclusions: Comorbidity status is predictive of perioperative death and 5-year all cause mortality after radical cystectomy and, therefore, should be incorporated into patient counseling and risk stratification models. Further prospective studies are warranted to overcome the retrospective limitations in determining the relative prognostic value of various comorbidity indices. References 1 : The effects of adjusting for case mix on mortality and length of stay following radical cystectomy. J Urol2006; 176: 1363. Link, Google Scholar 2 : A critical analysis of perioperative mortality from radical cystectomy. J Urol2006; 175: 886. Link, Google Scholar 3 : Contemporary open radical cystectomy: analysis of perioperative outcomes. J Urol2008; 179: 1313. Link, Google Scholar 4 : Risk factors for mortality and morbidity related to radical cystectomy. BJU Int2008; 103: 191. 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Google Scholar 11 : Predicting the probability of 90-day survival of elderly patients with bladder cancer treated with radical cystectomy. J Urol2011; 186: 829. Link, Google Scholar 12 : Contemporary trends of in-hospital complications and mortality for radical cystectomy. BJU Int2012; 110: 1163. Google Scholar 13 : Predictive capacity of four comorbidity indices estimating perioperative mortality after radical cystectomy for urothelial carcinoma of the bladder. BJU Int2012; 110: E222. Google Scholar 14 : Associations between comorbidity, and overall survival and bladder cancer specific survival after radical cystectomy: results from the Alberta Urology Institute Radical Cystectomy database. J Urol2009; 182: 85. Link, Google Scholar 15 : Comorbidity and performance indices as predictors of cancer-independent mortality but not of cancer-specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Eur Urol2012; 62: 662. Google Scholar 16 : Comorbidity in older surgical cancer patients: influence on patient care and outcome. Eur J Cancer2007; 43: 2179. Google Scholar 17 : The influence of comorbidities on overall survival among older women diagnosed with breast cancer. J Natl Cancer Inst2011; 103: 1101. Google Scholar 18 : Age-adjusted Charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer. Cancer2008; 112: 2384. Google Scholar 19 : Prognostic impact of comorbidity in patients with bladder cancer. Eur Urol2008; 53: 581. Google Scholar 20 : Impact of comorbidity on survival of invasive bladder cancer patients, 1996–2007: a Danish population-based cohort study. Urology2010; 75: 393. Google Scholar 21 : Grading of patients for surgical procedures. Anesthesiology1941; 2: 281. Google Scholar 22 : A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis1987; 40: 373. Crossref, Medline, Google Scholar 23 : Comorbidity measures for use with administrative data. Med Care1998; 36: 8. Google Scholar 24 : Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol1982; 5: 649. Google Scholar 25 : Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics1988; 44: 837. Google Scholar 26 : Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer2009; 115: 68. Google Scholar 27 : Impact of body mass index on radical cystectomy. J Urol2004; 172: 1281. Link, Google Scholar 28 : Impact of hospital and surgeon volume on in-hospital mortality from radical cystectomy: data from the Health Care Utilization Project. J Urol2005; 173: 1695. Link, Google Scholar 29 : The impact of co-morbid disease on cancer control and survival following radical cystectomy. J Urol2003; 169: 105. Link, Google Scholar 30 : A systematic review and meta-analysis of the relationship between hospital/surgeon volume and outcome for radical cystectomy: an update for the ongoing debate. Eur Urol2011; 59: 775. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byChang S (2015) Re: Conditional Survival after Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over TimeJournal of Urology, VOL. 195, NO. 3, (610-611), Online publication date: 1-Mar-2016.Chang S (2015) Re: Conditional Survival after Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over TimeJournal of Urology, Linder B, Tarrell R and Boorjian S (2014) Cystectomy for Refractory Hemorrhagic Cystitis: Contemporary Etiology, Presentation and OutcomesJournal of Urology, VOL. 192, NO. 6, (1687-1692), Online publication date: 1-Dec-2014.Eisenberg M, Boorjian S, Cheville J, Thompson R, Thapa P, Kaushik D and Frank I (2013) The SPARC Score: A Multifactorial Outcome Prediction Model for Patients Undergoing Radical Cystectomy for Bladder CancerJournal of Urology, VOL. 190, NO. 6, (2005-2010), Online publication date: 1-Dec-2013. Volume 190Issue 1July 2013Page: 55-60Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordscomorbidityurinary bladder neoplasmscystectomymortalitycarcinoma, transitional cellMetricsAuthor Information Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Novartis and Endo Pharmaceuticals. More articles by this author Simon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author Matthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author Alonso Carrasco Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author John C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author Prabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota Nothing to disclose. More articles by this author Igor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Rochester Medical Company. More articles by this author Expand All Advertisement PDF downloadLoading ...

Cryoablation (CA) is a minimally invasive modality with low complication rates, but its use in urology is relatively recent. To summarize available evidence for CA for small renal masses (SRMs) and to assess the selection criteria, complications, and functional and oncologic results based on the latest CA literature. A systematic literature search of the Medline, Embase, and Scopus databases was performed in August 2014 using Medical Subject Headings and free-text protocol. The following search terms were included: kidney cryosurgery, renal cryosurgery, kidney cryoablation, renal cryoablation, kidney cryotherapy, and renal cryotherapy. Due to the relatively recent mainstream utilization of CA and lack of long-term efficacy data from large prospective or randomized studies, most of the data available on CA are limited to treatment of SRMs in patients who are often older or are poor surgical candidates. The rates of major complications across the CA literature remain relatively low. Studies assessing renal function after CA suggest a degree of functional decline following CA because proper application includes freezing of a tumor margin; however, often this is not clinically significant. Specific oncologic outcomes should be evaluated in patients with biopsy-proven renal cell carcinoma; when SRM series include benign or unbiopsied tumors, the results of these outcomes are skewed. Although earlier series were suggestive of a higher recurrence rate after CA, some studies have challenged this view reporting recurrence rates comparable with extirpative nephron-sparing surgery. CA represents an alternative approach to treatment for patients diagnosed with renal neoplasm. There is no consensus within the literature on the best patient selection criteria. Due to higher rates of treatment failure, it is often not offered to patients with minimal comorbidities and good life expectancy. In terms of functional outcomes, CA signifies a modality with minimum impact on renal function; however, well-designed studies precisely assessing this factor are lacking. CA is a minimally invasive modality with suitably low rates of complications, particularly if delivered via the percutaneous route. Cryoablation (CA) represents an alternative approach for treating renal neoplasm. Excellent functional outcomes and low rates of complications make CA an ideal minimally invasive modality. Patient selection criteria and oncologic outcomes require further study.

We evaluate the association between severe skeletal muscle deficiency or sarcopenia, and disease progression, cancer specific mortality and all cause mortality in patients with localized renal cell carcinoma treated with radical nephrectomy.The baseline lumbar skeletal muscle index of 387 patients treated with radical nephrectomy for nonmetastatic renal cell carcinoma between 2000 and 2010 was measured on preoperative computerized tomography. Sarcopenia was classified according to gender specific consensus definitions as male-skeletal muscle index less than 55 cm(2)/m(2) and female-skeletal muscle index less than 39 cm(2)/m(2). Progression-free, cancer specific and overall survival was estimated with the Kaplan-Meier method. Associations with progression, cancer specific mortality and all cause mortality were summarized with hazard ratios.Of 387 patients 180 (47%) had sarcopenia. Patients with sarcopenia were older, more likely to be male (77% vs 56%, p <0.001), to have a smoking history (67% vs 55%, p=0.02), and to have nuclear grade 3 or greater disease (67% vs 60%, p=0.05), but were otherwise similar to patients without sarcopenia. Median postoperative followup was 7.2 years. Patients with sarcopenia had inferior 5-year cancer specific survival (79% vs 85%, p=0.05) compared to those without sarcopenia, as well as significantly worse 5-year overall survival (65% vs 74%, p= 0.005). As a continuous variable, increasing skeletal muscle index was linearly associated with a decreased risk of cancer specific mortality and all cause mortality. Moreover, on multivariable analysis sarcopenia was associated with increased cancer specific mortality (HR 1.70, p=0.047) and all cause mortality (HR 1.48, p=0.039).Sarcopenia is independently associated with cancer specific mortality and all cause mortality after radical nephrectomy for renal cell carcinoma. These findings underscore the importance of assessing skeletal muscle index for risk stratification, patient counseling and treatment planning.

Surgery for renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus above the hepatic veins is technically complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with poor outcomes. To determine the preoperative predictors of major complications and 90-d mortality after surgery in RCC patients who have IVC thrombus above the hepatic veins. We reviewed medical records of all RCC patients who had IVC tumor thrombus above hepatic veins and had had surgery between January 2000 and December 2012 at the Mayo Clinic, M.D. Anderson Cancer Center, University of Texas Southwestern Medical Center, and the University of Wisconsin Hospital. Major complications recorded were defined as ≥3A according to the Clavien-Dindo system within 90 d of surgery. Univariate and multivariate analyses were used to evaluate associations of preoperative variables with risk of major complications or 90-d mortality. A total of 162 patients were identified for study (level 3, 4 in 69, 93 patients, respectively, according to the Neves classification). Cardiopulmonary bypass was used in 60 of 162 patients (37.5%), and 40 patients (24.7%) had preoperative angioembolization. Major complications were reported in 55 patients (34.0%), with the most common being respiratory, cardiac, and hematologic issues. After multivariate analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with increased risk of major complications. Mortality was reported in 17 patients (10.5%) within 90 d after surgery. After multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and low serum albumin were preoperative factors independently associated with increased risk of 90-d mortality. Contemporary perioperative mortality and major complication rates for RCC patients who have upper-level thrombus are 10% and 34%, respectively. Patients who have ECOG PS >1 or low serum albumin have increased risk for perioperative mortality.

No AccessJournal of UrologyAdult Urology1 Jan 2017Outcomes Following Complete Surgical Metastasectomy for Patients with Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis Harras B. Zaid, William P. Parker, Nida S. Safdar, Boris Gershman, Patricia J. Erwin, M. Hassan Murad, Stephen A. Boorjian, Brian A. Costello, R. Houston Thompson, and Bradley C. Leibovich Harras B. ZaidHarras B. Zaid Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , William P. ParkerWilliam P. Parker Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , Nida S. SafdarNida S. Safdar Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , Boris GershmanBoris Gershman Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , Patricia J. ErwinPatricia J. Erwin Mayo Clinic Libraries, Mayo Clinic and Medical School, Rochester, Minnesota , M. Hassan MuradM. Hassan Murad Center for the Science of Health Care Delivery, Mayo Clinic and Medical School, Rochester, Minnesota , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , Brian A. CostelloBrian A. Costello Department of Oncology, Mayo Clinic and Medical School, Rochester, Minnesota , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota , and Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota View All Author Informationhttps://doi.org/10.1016/j.juro.2016.07.079AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The benefit of complete surgical metastasectomy for patients with metastatic renal cell carcinoma remains controversial due to limited outcome data. We performed a systematic review and meta-analysis to determine whether complete surgical metastasectomy confers a survival benefit compared to incomplete or no metastasectomy for patients with metastatic renal cell carcinoma. Materials and Methods: Ovid Embase®, MEDLINE®, Cochrane and Scopus® databases were searched for studies evaluating complete surgical metastasectomy for metastatic renal cell carcinoma through January 19, 2016. Only comparative studies reporting adjusted hazard ratios (aHRs) for all cause mortality of incomplete surgical metastasectomy vs complete surgical metastasectomy were included in the analysis. Generic inverse variance with random effects models was used to determine the pooled aHR. Risk of bias was assessed with the Newcastle-Ottawa Scale. Results: Eight published cohort studies with a low or moderate potential for bias were included in the final analysis. The studies reported on a total of 2,267 patients (958 undergoing complete surgical metastasectomy and 1,309 incomplete surgical metastasectomy). Median overall survival ranged between 36.5 and 142 months for those undergoing complete surgical metastasectomy, compared to 8.4 to 27 months for incomplete surgical metastasectomy. Complete surgical metastasectomy was associated with a reduced risk of all cause mortality compared with incomplete surgical metastasectomy (pooled aHR 2.37, 95% CI 2.03–2.87, p <0.001), with low heterogeneity (I2 = 0%). Complete surgical metastasectomy remained independently associated with a reduction in mortality across a priori subgroup and sensitivity analyses, and regardless of whether we adjusted for performance status. Conclusions: Complete surgical metastasectomy for metastatic renal cell carcinoma is associated with improved survival compared with incomplete surgical metastasectomy based on meta-analysis of observational data. Consideration should be given to performing complete surgical metastasectomy, when technically feasible, in patients with metastatic renal cell carcinoma who are surgical candidates. References 1 : Cancer statistics, 2016. CA Cancer J Clin2016; 66: 7. Google Scholar 2 : Incidental finding of renal masses at unenhanced CT: prevalence and analysis of features for guiding management. AJR Am J Roentgenol2011; 197: 139. Google Scholar 3 : Evaluation and management of the renal mass. Med Clin North Am2011; 95: 179. Google Scholar 4 : The changing natural history of renal cell carcinoma. J Urol2001; 166: 1611. Link, Google Scholar 5 : Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol2002; 20: 4559. Google Scholar 6 : Phase 3 trial of everolimus for metastatic renal cell carcinoma. Cancer2010; 116: 4256. Google Scholar 7 : Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med2015; 373: 1803. Google Scholar 8 : Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med2015; 373: 1814. Google Scholar 9 : Surgeon’s role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: an institutional review. Ann Surg Oncol1994; 1: 345. Google Scholar 10 : Kidney cancer, version 3.2015. J Natl Compr Canc Netw2015; 13: 151. Google Scholar 11 : The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol2009; 62: e1. Google Scholar 12 : Evaluating non-randomised intervention studies. Health Technol Assess2003; 7: iii. Google Scholar 13 : GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol2011; 64: 383. Google Scholar 14 : Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer2011; 117: 2873. Google Scholar 15 : Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma. J Urol2008; 180: 873. Link, Google Scholar 16 : Resection of metastatic renal cell carcinoma. J Clin Oncol1998; 16: 2261. Google Scholar 17 : Metastasectomy without systemic therapy in metastatic renal cell carcinoma: comparison with conservative treatment. Urol Int2007; 79: 145. Google Scholar 18 : Evaluation of a new prognostic score (Munich score) to predict long-term survival after resection of pulmonary renal cell carcinoma metastases. Am J Surg2011; 202: 158. Google Scholar 19 : Prognostic factors of patients with metastatic renal cell carcinoma with removed metastases: a multicenter study of 556 patients. Urology2013; 82: 846. Google Scholar 20 : Liver resection for metastatic disease prolongs survival in renal cell carcinoma: 12-year results from a retrospective comparative analysis. World J Urol2010; 28: 543. 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Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLyon T, Thompson R, Shah P, Lohse C, Boorjian S, Costello B, Cheville J and Leibovich B (2019) Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine EraJournal of Urology, VOL. 203, NO. 2, (275-282), Online publication date: 1-Feb-2020.Ristau B, Manola J, Haas N, Heng D, Messing E, Wood C, Kane C, DiPaola R and Uzzo R (2017) Retroperitoneal Lymphadenectomy for High Risk, Nonmetastatic Renal Cell Carcinoma: An Analysis of the ASSURE (ECOG-ACRIN 2805) Adjuvant TrialJournal of Urology, VOL. 199, NO. 1, (53-59), Online publication date: 1-Jan-2018.Smith J (2016) This Month in Adult UrologyJournal of Urology, VOL. 197, NO. 1, (1-3), Online publication date: 1-Jan-2017. Volume 197Issue 1January 2017Page: 44-49Supplementary Materials Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.Keywordscarcinomaneoplasm metastasismetastasectomyrenal cellMetricsAuthor Information Harras B. Zaid Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author William P. Parker Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Nida S. Safdar Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Boris Gershman Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Patricia J. Erwin Mayo Clinic Libraries, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author M. Hassan Murad Center for the Science of Health Care Delivery, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Brian A. Costello Department of Oncology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Bradley C. Leibovich Department of Urology, Mayo Clinic and Medical School, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

No AccessJournal of UrologyAdult Urology1 Mar 2014Long-Term Renal Function Outcomes after Radical Cystectomy Manuel S. Eisenberg, R. Houston Thompson, Igor Frank, Simon P. Kim, Katherine J. Cotter, Matthew K. Tollefson, Dharam Kaushik, Prabin Thapa, Robert Tarrell, and Stephen A. Boorjian Manuel S. EisenbergManuel S. Eisenberg Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Igor FrankIgor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Rochester Medical. More articles by this author , Simon P. KimSimon P. Kim Department of Urology, Yale University, New Haven, Connecticut More articles by this author , Katherine J. CotterKatherine J. Cotter Department of Urology, University of Minnesota, Minneapolis, Minnesota More articles by this author , Matthew K. TollefsonMatthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Dharam KaushikDharam Kaushik Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Prabin ThapaPrabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , Robert TarrellRobert Tarrell Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , and Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.09.011AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated the long-term natural history of renal function after radical cystectomy with urinary diversion and determined factors associated with decreased renal function. Materials and Methods: We reviewed the records of 1,631 patients who underwent radical cystectomy between 1980 and 2006. The estimated glomerular filtration rate was calculated preoperatively and at various intervals after surgery. A renal function decrease was defined as a greater than 10 ml per minute/1.73 m2 reduction in the estimated glomerular filtration rate. Multivariate analysis was done to evaluate the association of clinicopathological features, incontinent vs continent diversion type and postoperative complications with decreased renal function. Results: A total of 1,241 patients (76%) underwent incontinent diversion and 390 (24%) underwent continent diversion. Median followup after radical cystectomy in patients alive at last followup was 10.5 years (IQR 7.1, 15.3). The median preoperative estimated glomerular filtration rate was higher in the continent diversion cohort (67 vs 59 ml per minute/1.73 m2, p <0.0001). This difference was maintained until 7 years postoperatively, after which no difference was noted in renal function by diversion type. By 10 years after radical cystectomy the risk of a renal function decrease was similar for incontinent and continent diversion (71% and 74%, respectively, p = 0.13). On multivariate analysis risk factors associated with decreased renal function included age (HR 1.03, p <0.0001), preoperative estimated glomerular filtration rate (HR 1.05, p <0.0001), chronic hypertension (HR 1.2, p = 0.01), postoperative hydronephrosis (HR 1.2, p = 0.03), pyelonephritis (HR 1.3, p = 0.01) and ureteroenteric stricture (HR 1.6, p <0.0001). Conclusions: Decreased renal function is noted in most patients during long-term followup after radical cystectomy. Postoperative hydronephrosis, pyelonephritis and ureteroenteric stricture represent potentially modifiable factors associated with a decrease. Choice of urinary diversion was not independently associated with decreased renal function. References 1 Cancer Facts & Figures 2013. Atlanta: American Cancer Society2013. Google Scholar 2 : NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Fort Washington, Pennsylvania: National Comprehensive Cancer Network®2011. 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Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byGargollo P, Ahmed M, Prieto M, Butaney M, Cramer C, Joshi V, Heimbach J and Granberg C (2021) Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver ModelJournal of Urology, VOL. 206, NO. 1, (115-123), Online publication date: 1-Jul-2021.Li Q, Assel M, Benfante N, Pietzak E, Bagrodia A, Cha E, Dalbagni G and Coleman J (2017) Clinical Outcomes in Patients with Panurothelial Carcinoma Treated with Radical Nephroureterectomy Following Cystectomy for Metachronous RecurrenceJournal of Urology, VOL. 198, NO. 3, (546-551), Online publication date: 1-Sep-2017.Zabell J, Adejoro O, Konety B and Weight C (2014) Risk of End Stage Kidney Disease after Radical Cystectomy According to Urinary Diversion TypeJournal of Urology, VOL. 193, NO. 4, (1283-1287), Online publication date: 1-Apr-2015.Skinner E, Fairey A, Groshen S, Daneshmand S, Cai J, Miranda G and Skinner D (2015) Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder CancerJournal of Urology, VOL. 194, NO. 2, (433-440), Online publication date: 1-Aug-2015. Volume 191Issue 3March 2014Page: 619-625 Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordsurinary bladder neoplasmsrenal insufficiencycystectomyurinary diversionchronicpostoperative complicationsMetricsAuthor Information Manuel S. Eisenberg Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Igor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota Financial interest and/or other relationship with Rochester Medical. More articles by this author Simon P. Kim Department of Urology, Yale University, New Haven, Connecticut More articles by this author Katherine J. Cotter Department of Urology, University of Minnesota, Minneapolis, Minnesota More articles by this author Matthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Dharam Kaushik Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Prabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Robert Tarrell Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

While the probability of malignant versus benign histology based on renal tumor size has been described, this alone does not sufficiently inform decision-making in the modern era since indolent malignant tumors can be managed with active surveillance. To characterize the probability of aggressive versus indolent histology based on radiographic tumor size. We evaluated patients who underwent radical or partial nephrectomy at Mayo Clinic for a pT1-2, pNx/0, M0 solid renal tumor between 1990 and 2010. Pathology was reviewed by one genitourinary pathologist. High-grade clear-cell renal cell carcinoma (RCC), high-grade papillary RCC, collecting duct RCC, translocation-associated RCC, hereditary leiomyomatosis RCC, unclassified RCC, and malignant non-RCC tumors were all considered aggressive, as well as any tumors demonstrating coagulative necrosis (except low-grade papillary RCC) or sarcomatoid differentiation. The remaining benign and malignant tumors were considered indolent. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Logistic regression models were used to estimate the probability of malignant and aggressive histology based on tumor size. Sex-stratified analyses were also performed. Of the 2650 patients included, there were 1860 patients with indolent tumors (300 benign; 1560 malignant) and 790 with aggressive tumors. The 10-yr CSS was 96% for indolent malignant tumors and 81% for aggressive malignant tumors. The predicted percentages of any malignant histology as well as aggressive histology increased with tumor size. Specifically, 2 cm, 3 cm, and 4 cm tumors have an estimated 84%, 87%, and 88% likelihood of malignancy, respectively, and an 18%, 24%, and 29% likelihood of aggressive histology, respectively. For any given tumor size, men had a greater chance of aggressive histology than women. Potential limitations of this observational surgical cohort include selection bias. We present tumor size-based estimates of the probability of aggressive histology for renal masses. This information should be useful for initial patient counseling and management. Active surveillance is an option for kidney masses, even if they are malignant. Beyond knowing whether the mass is benign or cancer, it is important to know whether or not it is an aggressive tumor. This study presents tumor size-specific and sex-specific estimates of the probability of cancer overall and aggressive cancer among patients with a kidney mass in order to aid with initial decision-making.

Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.

Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) and ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal losses can generate proteotoxic stress and compromise cellular proliferation, it is intriguing how chRCC, a tumor with extensive chromosome losses and a low number of somatic mutations, can develop lethal metastases. Genomic features distinguishing metastatic from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS), targeted ultradeep cancer gene sequencing, and chromosome analyses (FACETS, OncoScan, and FISH), was performed on 79 chRCC patients including 38 metastatic (M-chRCC) cases. We demonstrate that TP53 mutations (58%), PTEN mutations (24%), and imbalanced chromosome duplication (ICD, duplication of ≥ 3 chromosomes) (25%) were enriched in M-chRCC. Reconstruction of the subclonal composition of paired primary-metastatic chRCC tumors supports the role of TP53, PTEN, and ICD in metastatic evolution. Finally, the presence of these 3 genomic features in primary tumors of both The Cancer Genome Atlas kidney chromophobe (KICH) (n = 64) and M-chRCC (n = 35) cohorts was associated with worse survival. In summary, our study provides genomic insights into the metastatic progression of chRCC and identifies TP53 mutations, PTEN mutations, and ICD as high-risk features.

The tumor stage, size, grade, and necrosis (SSIGN) score was originally defined using patients treated with radical nephrectomy (RN) between 1970 and 1998 for clear cell renal cell carcinoma (ccRCC), excluding patients treated with partial nephrectomy (PN).To characterize the original SSIGN score cohort with longer follow-up and evaluate a contemporary series of patients treated with RN and PN.Retrospective single-institution review of 3600 consecutive surgically treated ccRCC patients grouped into three cohorts: original RN, contemporary (1999-2010) RN, and contemporary PN.RN or PN.The association of the SSIGN score with risk of death from RCC was assessed using a Cox proportional hazards regression model, and predictive ability was summarized with a C-index.The SSIGN scores differed significantly between the original RN, contemporary RN, and contemporary PN cohorts (p<0.001), with SSIGN ≥4 in 53.5%, 62.7%, and 4.7%, respectively (p<0.001). The median durations of follow-up for these groups were 20.1, 9.2, and 7.6 yr, respectively. Each increase in the SSIGN score was predictive of death from RCC (hazard ratios [HRs]: 1.41 for original RN, 1.37 for contemporary RN, and 1.70 for contemporary PN; all p<0.001). The C-indexes for these models were 0.82, 0.84, and 0.82 for original RN, contemporary RN, and contemporary PN, respectively. After accounting for an era-specific improvement in survival among RN patients (HR: 0.53 for contemporary vs original RN; p<0.001), the SSIGN score remained predictive of death from RCC (HR: 1.40; p<0.001).The SSIGN score remains a useful prediction tool for patients undergoing RN with 20-yr follow-up. When applied to contemporary RN and PN patients, the score retained strong predictive ability. These results should assist in patient counseling and help guide surveillance for ccRCC patients treated with RN or PN.We evaluated the validity of a previously described tool to predict survival following surgery in contemporary patients with kidney cancer. We found that this tool remains valid even when extended to patients significantly different than were initially used to create the tool.

Our objective was to evaluate the role of retroperitoneal lymph node dissection (LND) in non-metastatic (M0) and metastatic (M1) renal cell carcinoma (RCC). We searched Medline, EMBASE, Web of Science and Scopus from database inception to 29 August 2017 for studies of patients who underwent partial or radical nephrectomy for M0 or M1 RCC. Two investigators independently selected studies for inclusion. Risk of bias was assessed using the Newcastle-Ottawa scale, Cochrane Collaboration tool and National Heart, Lung and Blood Institute Quality Assessment Tool. Random effects meta-analysis was performed for all-cause-mortality. The GRADE approach was used to characterize quality of evidence. A total of 51 unique studies were included in the qualitative systematic review. Risk of bias was low in 41/51 (80%) studies. LND was not associated with all-cause mortality in either M0 (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.92-1.12; I2 = 0%; four studies), M1 (HR 1.04, 95% CI 0.83-1.29; I2 = 0%; two studies), or pooled M0 and M1 settings (HR 1.00, 95% CI 0.92-1.09; I2 = 0%; seven studies), with no statistically significant differences according to M stage subgroups (P = 0.50). In the three studies that examined M0 subgroups with a high risk of nodal metastasis, LND was not associated with improved oncological outcomes. Studies on the association of extent of LND with survival reported inconsistent results. Meanwhile, a small proportion of patients with pN1M0 disease demonstrate durable long-term oncological control after surgery, with 10-year cancer-specific survival of 21-31%. Nodal involvement is independently associated with adverse prognosis in both M0 and M1 settings. GRADE quality of evidence was moderate or low for the outcomes examined. Although LND yields independent prognostic information, the existing literature does not support a therapeutic benefit to LND in either M0 or M1 RCC. High-risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long-term survival after surgical resection.

No AccessJournal of UrologyAdult Urology1 Oct 2014Oncologic Outcomes Following Surgical Resection of Renal Cell Carcinoma with Inferior Vena Caval Thrombus Extending Above the Hepatic Veins: A Contemporary Multicenter Cohort Ahmed Q. Haddad, Christopher G. Wood, E. Jason Abel, Laura-Maria Krabbe, Oussama M. Darwish, R. Houston Thompson, Jennifer E. Heckman, Megan M. Merril, Bishoy A. Gayed, Arthur I. Sagalowsky, Stephen A. Boorjian, Vitaly Margulis, and Bradley C. Leibovich Ahmed Q. HaddadAhmed Q. Haddad Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , Christopher G. WoodChristopher G. Wood Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas Financial interest and/or other relationship with Pfizer and Argos. More articles by this author , E. Jason AbelE. Jason Abel Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin More articles by this author , Laura-Maria KrabbeLaura-Maria Krabbe Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Urology, University of Muenster Medical Center, Muenster, Germany More articles by this author , Oussama M. DarwishOussama M. Darwish Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author , Jennifer E. HeckmanJennifer E. Heckman Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin More articles by this author , Megan M. MerrilMegan M. Merril Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas More articles by this author , Bishoy A. GayedBishoy A. Gayed Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , Arthur I. SagalowskyArthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with the American Urological Association, The Journal of Urology, Urologic Oncology and Current Urology Reports. More articles by this author , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author , Vitaly MargulisVitaly Margulis Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , and Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.03.111AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Suprahepatic inferior vena caval tumor thrombus in renal cell carcinoma cases has historically portended a poor prognosis. With advances in perioperative treatment of patients with high level thrombus contemporary outcomes are hypothesized to be improved. We evaluated long-term oncologic outcomes of contemporary surgical treatment of patients with renal cell carcinoma in whom level III-IV inferior vena caval thrombus was managed at high volume centers. Materials and Methods: We examined clinical and pathological data on patients with renal cell carcinoma and level III-IV thrombus treated with surgery from January 2000 to June 2013 at 4 tertiary referral centers. Survival outcomes and associated prognostic variables were assessed by Kaplan-Meier and multivariate Cox regression analyses. Results: We identified 166 patients, including 69 with level III and 97 with level IV thrombus. Median postoperative followup was 27.8 months. Patients with no evidence of nodal or distant metastasis (pN0/X, M0) had 5-year 49.0% cancer specific survival and 42.2% overall survival. There was no difference in survival based on tumor thrombus level or pathological tumor stage. Variables associated with an increased risk of death from kidney cancer on multivariate analysis were regional nodal metastases (HR 3.94, p <0.0001), systemic metastases (HR 2.39, p = 0.01), tumor grade 4 (HR 2.25, p = 0.02), histological tissue necrosis (HR 3.11, p = 0.004) and increased preoperative serum alkaline phosphatase (HR 2.30, p = 0.006). Conclusions: Contemporary surgical management achieves almost 50% 5-year survival in patients without metastasis who have renal cell carcinoma thrombus above the hepatic veins. Factors associated with increased mortality included nodal/distant metastases, advanced grade, histological necrosis and increased preoperative serum alkaline phosphatase. These findings support an aggressive surgical approach to the treatment of patients with renal cell carcinoma who have advanced tumor thrombus. References 1 : Cancer statistics, 2013. CA Cancer J Clin2013; 63: 11. 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Google Scholar 14 : Techniques for avoidance of sternotomy and cardiopulmonary bypass during resection of extensive renal cell carcinoma with vena caval tumor thrombus extension above the diaphragm. J Card Surg2009; 24: 657. Google Scholar 15 : Preoperative metastatic status, level of thrombus and body mass index predict overall survival in patients undergoing nephrectomy and inferior vena cava thrombectomy. BJU Int2012; 110: E470. Google Scholar 16 : Renal cell carcinoma with tumor thrombus extension into the vena cava: prospective long-term followup. J Urol2007; 177: 1703. Link, Google Scholar 17 : The surgical management and prognosis of renal cell cancer with IVC tumor thrombus: 15-years of experience using a multi-specialty approach at a single UK referral center. Urol Oncol2013; 31: 1298. Google Scholar 18 : Renal cell carcinoma with inferior vena caval extension: impact of tumour extent on surgical outcome. BJU Int2009; 104: 1467. 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Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byXie L, Hong G, Nabavizadeh R, Patil D, Ethun C, Ogan K, Maithel S and Master V (2020) Outcomes in Patients with Renal Cell Carcinoma Undergoing Inferior Vena Cava Ligation without Reconstruction versus Thrombectomy: A Retrospective, Case Controlled StudyJournal of Urology, VOL. 205, NO. 2, (383-391), Online publication date: 1-Feb-2021.Liu N, Wren J, Vertosick E, Lee J, Power N, Benfante N, Kimm S, Bains M, Sjoberg D, Russo P and Coleman J (2015) The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 195, NO. 2, (264-269), Online publication date: 1-Feb-2016. Volume 192Issue 4October 2014Page: 1050-1056Supplementary Materials Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordscarcinomakidneyinferiorvena cavamortalitythrombosisrenal cellMetricsAuthor Information Ahmed Q. Haddad Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Christopher G. Wood Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas Financial interest and/or other relationship with Pfizer and Argos. More articles by this author E. Jason Abel Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin More articles by this author Laura-Maria Krabbe Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Urology, University of Muenster Medical Center, Muenster, Germany More articles by this author Oussama M. Darwish Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author R. Houston Thompson Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Jennifer E. Heckman Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin More articles by this author Megan M. Merril Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas More articles by this author Bishoy A. Gayed Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Arthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with the American Urological Association, The Journal of Urology, Urologic Oncology and Current Urology Reports. More articles by this author Stephen A. Boorjian Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Vitaly Margulis Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Bradley C. Leibovich Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n=324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90% vs 94%; p=1), cancer-specific survival (CSS; 82% vs 93%; p=0.4), and overall survival (OS; 82% vs 82%; p=0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n=103). Conversely, among patients with rUCB at RC (n=401), patients who received NAC had significantly worse 5-yr RFS (50% vs 63%; p=0.01), CSS (40% vs 59%; p=0.003), and OS (33% vs 48%; p=0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.28-2.66; p=0.001), CSS (HR 1.81, 95% CI 1.30-2.52; p<0.001), and OS (HR 1.57, 95% CI 1.18-2.08; p=0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC.On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer.

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit. To develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30 d following PN and RN, separately. In this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR <15 ml/min/1.73 m2. RN and PN. Hierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal RGLMM2, which ranges from 0 to 1, with higher values indicating increased predictive ability. The analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66 ml/min/1.73 m2 (standard deviation [SD] = 18) and 72 ml/min/1.73 m2 (SD = 20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal RGLMM2=0.41). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal RGLMM2). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts. We developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making. We developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors.

Although clear cell renal cell carcinoma (ccRCC) has been shown to result in widespread aberrant cytosine methylation and loss of 5-hydroxymethylcytosine (5hmC), the prognostic impact and therapeutic targeting of this epigenetic aberrancy has not been fully explored. Analysis of 576 primary ccRCC samples demonstrated that loss of 5hmC was strongly associated with aggressive clinicopathologic features and was an independent adverse prognostic factor. Loss of 5hmC also predicted reduced progression-free survival after resection of nonmetastatic disease. The loss of 5hmC in ccRCC was not due to mutational or transcriptional inactivation of ten eleven translocation (TET) enzymes, but to their functional inactivation by l-2-hydroxyglutarate (L2HG), which was overexpressed due to the deletion and underexpression of L2HG dehydrogenase (L2HGDH). Ascorbic acid (AA) reduced methylation and restored genome-wide 5hmC levels via TET activation. Fluorescence quenching of the recombinant TET-2 protein was unaffected by L2HG in the presence of AA. Pharmacologic AA treatment led to reduced growth of ccRCC in vitro and reduced tumor growth in vivo, with increased intratumoral 5hmC. These data demonstrate that reduced 5hmC is associated with reduced survival in ccRCC and provide a preclinical rationale for exploring the therapeutic potential of high-dose AA in ccRCC.

Open nephron sparing surgery (NSS) is now the standard of care for small renal tumors irrespective of overall renal function. More recently laparoscopic NSS with hilar clamping has emerged, albeit with relatively longer ischemic times. We reviewed our experience with contemporary open NSS, comparing complication rates to those of historical controls and updating data for comparison with minimally invasive procedures.From 1985 to 2001, 823 open NSSs were performed at our institution. Early (within 30 days of NSS) and late (30 days to 1 year) complications were compared using the chi-square and Wilcoxon rank sum tests between procedures performed in 1985 to 1995 (control group of 343 patients) and 1996 to 2001 (contemporary group of 480).In the control vs the contemporary group there were significant decreases in intraoperative blood loss (median 550 vs 350 cc, p <0.001), chronic renal insufficiency/failure (14.6% vs 8.1%, p = 0.003), dialysis need (7.0% vs 2.1%, p <0.001) and any early (13.4% vs 6.9%, p = 0.002) or late (32.4% vs 24.6%, p = 0.014) complication. In the contemporary group 50% of patients did not require pedicle clamping, 32% underwent warm ischemia (median 12 minutes) and 18% underwent cold ischemia (median 27 minutes). In addition, patients with a warm ischemia time of 20 minutes or less had fewer early complications than patients with greater than 20 minutes of ischemia, although this did not attain statistical significance (3.8% vs 13.6%, p = 0.063).Complications resulting from open NSS have significantly decreased with time. Contemporary open NSS is associated with minimal morbidity, and decreases the need for pedicle clamping and overall ischemia time.

No AccessJournal of UrologyAdult Urology1 Nov 2009Prognostic Impact of Histological Subtype on Surgically Treated Localized Renal Cell Carcinoma Patrick E. Teloken, R. Houston Thompson, Satish K. Tickoo, Angel Cronin, Caroline Savage, Victor E. Reuter, and Paul Russo Patrick E. TelokenPatrick E. Teloken More articles by this author , R. Houston ThompsonR. Houston Thompson More articles by this author , Satish K. TickooSatish K. Tickoo More articles by this author , Angel CroninAngel Cronin More articles by this author , Caroline SavageCaroline Savage More articles by this author , Victor E. ReuterVictor E. Reuter More articles by this author , and Paul RussoPaul Russo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.07.019AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Despite the clear demonstration that different histological subtypes of renal cell carcinoma show distinct pathogenesis and genetic alterations, the impact of histology on prognosis remains controversial. We evaluated our experience with tumor histology in patients with localized renal cell carcinoma. Materials and Methods: We identified 1,863 patients with localized clear cell, papillary or chromophobe renal cell carcinoma who were treated surgically between 1989 and 2006 at our tertiary care center. Cox proportional hazards regression models were used to evaluate the relationship between tumor histology and outcome, defined as metastasis or death from disease, adjusting for age, sex, operation type, American Society of Anesthesiologists score, TNM stage and tumor size. Results: Of 1,863 patients 1,333 (72%) had clear cell histology, and 310 (17%) and 220 (12%) had papillary and chromophobe renal cell carcinoma, respectively. Median followup in patients without an event was 3.4 years. On univariate analysis patients with clear cell histology had a worse clinical outcome. Five-year probability of freedom from metastasis or death from disease was 86% (95% CI 84, 88), 95% (95% CI 91, 97) and 92% (95% CI 85, 96) in patients with clear cell, papillary and chromophobe histology, respectively (p <0.001). On multivariate analysis chromophobe (HR 0.40; 95% CI 0.20, 0.80) and papillary (HR 0.62; 95% CI 0.34, 1.14) histology was also significantly associated with better outcome (p = 0.014). Conclusions: Clear cell histology seems to be independently associated with worse outcomes in patients who undergo surgery for renal cell carcinoma even after controlling for widely accepted factors influencing prognosis. References 1 : The Heidelberg classification of renal cell tumours. J Pathol1997; 183: 131. Google Scholar 2 : The pathology of renal epithelial neoplasms. Semin Oncol2006; 33: 534. Google Scholar 3 : Molecular classification of renal tumors by gene expression profiling. J Mol Diagn2005; 7: 206. Google Scholar 4 : Robust classification of renal cell carcinoma based on gene expression data and predicted cytogenetic profiles. Cancer Res2004; 64: 4117. Google Scholar 5 : Renal-cell carcinoma. N Engl J Med2005; 353: 2477. Google Scholar 6 : Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol2003; 27: 612. Google Scholar 7 : Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Ann Surg Oncol2004; 11: 71. Google Scholar 8 : Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol2005; 23: 2763. Google Scholar 9 : A postoperative prognostic nomogram for renal cell carcinoma. J Urol2001; 166: 63. Link, Google Scholar 10 : Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol2004; 22: 3316. Google Scholar 11 : Prognostic factors in renal cell carcinoma. Semin Oncol2006; 33: 563. Google Scholar 12 : Preoperative nomogram predicting 12-year probability of metastatic renal cancer. J Urol2008; 179: 2146. Link, Google Scholar 13 : An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol2002; 168: 2395. Link, Google Scholar 14 : Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness. Cancer2005; 104: 511. Google Scholar 15 : Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma. Cancer2005; 103: 2517. Google Scholar 16 : Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases. Am J Surg Pathol2002; 26: 281. Google Scholar 17 : Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype. Pathology2007; 39: 459. Google Scholar 18 : AJCC Cancer Staging Manual. New York: Springer Press2002. Google Scholar 19 : Targeted therapies for kidney cancer in urologic practice. Urol Oncol2007; 25: 420. Google Scholar 20 : Prognostic role of the histologic subtypes of renal cell carcinoma after slide revision. Eur Urol2006; 50: 786. Google Scholar 21 : Pathologic features of renal cortical tumors. Urol Clin North Am2008; 35: 551. Google Scholar 22 : Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. Am J Clin Pathol2002; 118: 877. Google Scholar Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York© 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited byDaugherty M, Blakely S, Shapiro O, Vourganti S, Mollapour M and Bratslavsky G (2015) Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER DatabaseJournal of Urology, VOL. 195, NO. 4 Part 1, (847-851), Online publication date: 1-Apr-2016.Hamilton R, Morilla D, Cabrera F, Leapman M, Chen L, Bernstein M, Hakimi A, Reuter V and Russo P (2018) The Association between Statin Medication and Progression after Surgery for Localized Renal Cell CarcinomaJournal of Urology, VOL. 191, NO. 4, (914-919), Online publication date: 1-Apr-2014.de Martino M, Pantuck A, Hofbauer S, Waldert M, Shariat S, Belldegrun A and Klatte T (2018) Prognostic Impact of Preoperative Neutrophil-to-Lymphocyte Ratio in Localized Nonclear Cell Renal Cell CarcinomaJournal of Urology, VOL. 190, NO. 6, (1999-2004), Online publication date: 1-Dec-2013.Sukov W, Lohse C, Leibovich B, Thompson R and Cheville J (2018) Clinical and Pathological Features Associated With Prognosis in Patients With Papillary Renal Cell CarcinomaJournal of Urology, VOL. 187, NO. 1, (54-59), Online publication date: 1-Jan-2012.Keegan K, Schupp C, Chamie K, Hellenthal N, Evans C and Koppie T (2018) Histopathology of Surgically Treated Renal Cell Carcinoma: Survival Differences by Subtype and StageJournal of Urology, VOL. 188, NO. 2, (391-397), Online publication date: 1-Aug-2012. Volume 182Issue 5November 2009Page: 2132-2136 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordscarcinomarenal cellpathologyprognosiskidneyMetricsAuthor Information Patrick E. Teloken More articles by this author R. Houston Thompson More articles by this author Satish K. Tickoo More articles by this author Angel Cronin More articles by this author Caroline Savage More articles by this author Victor E. Reuter More articles by this author Paul Russo More articles by this author Expand All Advertisement PDF downloadLoading ...

The 2002 primary tumor classification for renal cell carcinoma (RCC) does not distinguish between patients with tumor thrombus involving the renal vein only and those with inferior vena cava tumor thrombus below the diaphragm. We evaluated the association of tumor thrombus level and fat invasion with outcome to determine if further subclassification would improve the prognostic accuracy of the current classification.We studied 675 patients treated with radical nephrectomy or nephron sparing surgery for pT3a (206, 30.5%), pT3b (422, 62.5%), pT3c (19, 2.8%) or pT4 (28, 4.2%) RCC at the Mayo Clinic between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression.There were 531 deaths from RCC at a median of 1.5 years following nephrectomy. Patients with pT3b RCC and level I, II or III tumor thrombus were significantly more likely to die of RCC compared to patients with pT3b RCC and level 0 tumor thrombus (risk ratio 1.62, p <0.001). Patients with peripheral perinephric or renal sinus fat invasion were also more likely to die of RCC compared to patients without fat invasion (risk ratio 1.87, p <0.001). Therefore, patients with pT3 RCC were reclassified into 4 groups as thrombus level 0 without fat invasion, fat invasion only, thrombus level 0 with fat invasion or thrombus level I, II or III without fat invasion, and thrombus level I, II or III with fat invasion or thrombus level IV. This reclassification significantly improved prediction of death from RCC compared with the current classification (c indexes of 0.61 versus 0.55, respectively).Further subclassification of the primary tumor classification for patients with pT3 RCC improved prognostic accuracy.

No AccessJournal of UrologyAdult Urology1 Jun 2008Preoperative Nomogram Predicting 12-Year Probability of Metastatic Renal Canceris accompanied byWho Will Fail Local Therapy for Renal Cell CarcinomaBPDE Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk Ganesh V. Raj, R. Houston Thompson, Bradley C. Leibovich, Michael L. Blute, Paul Russo, and Michael W. Kattan Ganesh V. RajGanesh V. Raj Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, UT Southwestern Medical Center, Dallas, Texas More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author , Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author , Michael L. BluteMichael L. Blute Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author , Paul RussoPaul Russo Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , and Michael W. KattanMichael W. Kattan Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.01.101AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: For patients with renal masses localized to the kidney there is currently no preoperative tool to predict the likelihood of metastatic recurrence following surgical intervention. We developed a predictive model that could be used in the preoperative setting. Materials and Methods: We pooled institutional databases from Memorial Sloan-Kettering and Mayo Clinic, and identified complete data on 2,517 patients with renal masses and no concurrent evidence of metastases who underwent radical or partial nephrectomy. Cox proportional hazard regression analyses were used to model preoperative clinical and radiographic characteristics as predictors for development of metastases following nephrectomy. Internal validation was performed with a statistical bootstrapping technique. Results: Metastatic recurrence developed in 340 of the 2,517 patients. Median followup for patients without metastatic recurrence was 4.7 years. A nomogram was developed using preoperative characteristics to predict the 12-year likelihood of postoperative metastatic recurrence with a concordance index of 0.80. In contrast, the concordance index of preoperative TNM staging was 0.71. Size of the primary renal mass, evidence of lymphadenopathy or necrosis on preoperative imaging and the mode of presentation were important predictors for the subsequent development of metastases. Conclusions: We present a preoperative nomogram that accurately predicts the development of metastatic recurrence following nephrectomy. This nomogram may be potentially useful to identify and counsel patients at high risk for recurrence. References 1 : Cancer statistics, 2007. CA Cancer J Clin2007; 57: 43. Google Scholar 2 : Renal-cell carcinoma. N Engl J Med1996; 335: 865. Google Scholar 3 : Surgical management of renal cell carcinoma. Semin Oncol2006; 33: 552. Google Scholar 4 : The evolving presentation of renal carcinoma in the United States: trends from the Surveillance, Epidemiology, and End Results program. J Urol2006; 176: 2397. Link, Google Scholar 5 : The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol2006; 175: 425. Link, Google Scholar 6 : Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy. J Clin Oncol1994; 12: 206. Google Scholar 7 Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial: Medical Research Council Renal Cancer Collaborators. Lancet1999; 353: 14. Google Scholar 8 : A postoperative prognostic nomogram for renal cell carcinoma. J Urol2001; 166: 63. Link, Google Scholar 9 Lam JS, Shvarts O, Leppert JT, Pantuck AJ, Figlin RA and Belldegrun AS: Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system. J Urol 174: 466. Google Scholar 10 : Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol2004; 22: 3316. Google Scholar 11 : Prognostic factors in renal cell carcinoma. Semin Oncol2006; 33: 563. Google Scholar 12 : Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol2001; 19: 1649. Crossref, Medline, Google Scholar 13 : An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol2002; 168: 2395. Link, Google Scholar 14 : Conservative management of incidental contrast-enhancing renal masses as safe alternative to invasive therapy. Urology2004; 64: 49. Google Scholar 15 : Minimally invasive ablative approaches in the treatment of renal cell carcinoma. Curr Urol Rep2002; 3: 13. Google Scholar 16 : Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study. Cancer2005; 104: 1362. Google Scholar 17 : Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin Cancer Res2004; 10: 6282S. Google Scholar 18 : Targeted for destruction: the molecular basis for development of novel therapeutic strategies in renal cell cancer. J Clin Oncol2005; 23: 410. Google Scholar 19 : Sunitinib in patients with metastatic renal cell carcinoma. JAMA2006; 295: 2516. Google Scholar 20 : Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncol2007; 8: 304. Google Scholar © 2008 by American Urological AssociationFiguresReferencesRelatedDetailsCited byRusso P (2020) Editorial CommentJournal of Urology, VOL. 204, NO. 3, (441-441), Online publication date: 1-Sep-2020.Hinz S, Weikert S, Magheli A, Hoffmann M, Engers R, Miller K and Kempkensteffen C (2009) Expression Profile of the Polycomb Group Protein Enhancer of Zeste Homologue 2 and its Prognostic Relevance in Renal Cell CarcinomaJournal of Urology, VOL. 182, NO. 6, (2920-2925), Online publication date: 1-Dec-2009.Teloken P, Thompson R, Tickoo S, Cronin A, Savage C, Reuter V and Russo P (2009) Prognostic Impact of Histological Subtype on Surgically Treated Localized Renal Cell CarcinomaJournal of Urology, VOL. 182, NO. 5, (2132-2136), Online publication date: 1-Nov-2009.Thompson R, Hill J, Babayev Y, Cronin A, Kaag M, Kundu S, Bernstein M, Coleman J, Dalbagni G, Touijer K and Russo P (2009) Metastatic Renal Cell Carcinoma Risk According to Tumor SizeJournal of Urology, VOL. 182, NO. 1, (41-45), Online publication date: 1-Jul-2009.Margulis V and Wood C (2009) Editorial CommentJournal of Urology, VOL. 181, NO. 3, (1027-1027), Online publication date: 1-Mar-2009.Kanao K, Mizuno R, Kikuchi E, Miyajima A, Nakagawa K, Ohigashi T, Nakashima J and Oya M (2008) Preoperative Prognostic Nomogram (Probability Table) for Renal Cell Carcinoma Based on TNM ClassificationJournal of Urology, VOL. 181, NO. 2, (480-485), Online publication date: 1-Feb-2009.Related articlesJournal of Urology18 Apr 2008Who Will Fail Local Therapy for Renal Cell CarcinomaJournal of Urology23 Apr 2008BPDE Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk Volume 179Issue 6June 2008Page: 2146-2151 Advertisement Copyright & Permissions© 2008 by American Urological AssociationKeywordsrenal cellneoplasm metastasiscarcinomanomogramsnephrectomyMetricsAuthor Information Ganesh V. Raj Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, UT Southwestern Medical Center, Dallas, Texas More articles by this author R. Houston Thompson Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author Bradley C. Leibovich Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author Michael L. Blute Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota More articles by this author Paul Russo Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Michael W. Kattan Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Department of Urology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio More articles by this author Expand All Advertisement PDF downloadLoading ...

No AccessJournal of UrologyAdult Urology1 Oct 2008Renal Cell Carcinoma in Young and Old Patients—Is There a Difference?is accompanied byA Novel Technique for Creating Solid Renal Pseudotumors and Renal Vein-Inferior Vena Caval Pseudothrombus in a Porcine and Cadaveric Model R. Houston Thompson, Maria A. Ordonez, Alexia Iasonos, Fernando P. Secin, Bertrand Guillonneau, Paul Russo, and Karim Touijer R. Houston ThompsonR. Houston Thompson Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , Maria A. OrdonezMaria A. Ordonez State University of New York Downstate Medical School, New York, New York More articles by this author , Alexia IasonosAlexia Iasonos Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , Fernando P. SecinFernando P. Secin Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , Bertrand GuillonneauBertrand Guillonneau Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , Paul RussoPaul Russo Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author , and Karim TouijerKarim Touijer Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.06.037AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Renal cell carcinoma is rare in patients younger than 40 years and conflicting data regarding presentation and outcome are present in the literature. We reviewed our experience with young patients with renal cell carcinoma and compared them to their older counterparts. Materials and Methods: We identified 1,720 patients 18 to 79 years old who were treated with partial or radical nephrectomy for renal cell carcinoma between 1989 and 2005. Patients were grouped according to age and outcome analysis was performed. Results: Of the 1,720 patients with renal cell carcinoma 89 (5%), 672 (39%) and 959 (56%) were younger than 40, 40 to 59 and 60 to 79 years old, respectively. There were no significant differences in sex, tumor size, TNM stage or multifocality by age group. However, patients younger than 40 years were significantly more likely to present with symptomatic tumors (p = 0.028). Additionally, there were significant differences in histology by age (p <0.001), that is chromophobe histology decreased while papillary histology increased with age. Despite similar tumor sizes in each age group the percent of patients treated with partial nephrectomy decreased with age. Of patients younger than 40 years 49% were treated with partial nephrectomy compared with 35% and 30% of those 40 to 59 and 60 to 79 years old, respectively (p <0.001). At a median followup of 2.6 years (range 0 to 14.5) we did not observe a significant difference in cancer specific survival according to age (p = 0.17). Conclusions: Younger patients with renal cell carcinoma are more likely to have symptomatic tumors with chromophobe histology, although the prognosis appears similar across age groups. Older patients are more likely to be treated with radical nephrectomy, which requires careful scrutiny for current clinical practice. References 1 : Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses. J Urol2005; 173: 1893. Link, Google Scholar 2 : Renal cell carcinoma in adults 40 years old or less: young age is an independent prognostic factor for cancer-specific survival. Eur Urol2007; 51: 980. Google Scholar 3 : Young age is an independent prognostic factor for survival of sporadic renal cell carcinoma. J Urol2004; 171: 2160. Link, Google Scholar 4 : Natural history and clinical outcome of sporadic renal cortical tumors diagnosed in the young adult. Urology2004; 63: 41. Google Scholar 5 : Renal cell carcinoma in young adults: incidence, disease outcome and review of the literature. Arch Esp Urol2002; 55: 969. Google Scholar 6 : Renal adenocarcinoma in young adults. Urology1985; 25: 357. Google Scholar 7 : Renal adenocarcinoma in young patients. Actas Urol Esp1997; 21: 22. Google Scholar 8 : Renal cell carcinoma in young and old patients: Comparison of prognostic pathologic variables (cell type, tumor grade and stage, and DNA ploidy pattern) and their impact on disease outcome. Urology1991; 38: 1. Google Scholar 9 : Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc2000; 75: 1236. Google Scholar 10 : Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol2006; 7: 735. Google Scholar 11 : Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol2008; 179: 468. Link, Google Scholar 12 : Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med2004; 351: 1296. Google Scholar 13 : Renal and cardiovascular morbidity after partial or radical nephrectomy. Cancer2007; 112: 511. Google Scholar 14 : Renal tumors in young adults. J Urol2004; 171: 106. Link, Google Scholar 15 : Sporadic renal cell carcinoma in young adults: presentation, treatment, and outcome. Urology2002; 60: 806. 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Google Scholar © 2008 by American Urological AssociationFiguresReferencesRelatedDetailsCited byGriebling T (2018) Re: Efficacy and Safety of Axitinib in Elderly Patients with Metastatic Renal Cell CarcinomaJournal of Urology, VOL. 197, NO. 2, (316-317), Online publication date: 1-Feb-2017.Daugherty M, Blakely S, Shapiro O, Vourganti S, Mollapour M and Bratslavsky G (2015) Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER DatabaseJournal of Urology, VOL. 195, NO. 4 Part 1, (847-851), Online publication date: 1-Apr-2016.Aziz A, May M, Zigeuner R, Pichler M, Chromecki T, Cindolo L, Schips L, De Cobelli O, Rocco B, De Nunzio C, Tubaro A, Coman I, Truss M, Dalpiaz O, Hoschke B, Gilfrich C, Feciche B, Fenske F, Sountoulides P, Figenshau R, Madison K, Sánchez-Chapado M, del Carmen Santiago Martin M, Wieland W, Salzano L, Lotrecchiano G, Waidelich R, Stief C and Brookman-May S (2018) Do Young Patients with Renal Cell Carcinoma Feature a Distinct Outcome after Surgery? A Comparative Analysis of Patient Age Based on the Multinational CORONA DatabaseJournal of Urology, VOL. 191, NO. 2, (310-315), Online publication date: 1-Feb-2014.Hew M, Zonneveld R, Kümmerlin i, Opondo D, de la Rosette J and Laguna M (2018) Age and Gender Related Differences in Renal Cell Carcinoma in a European CohortJournal of Urology, VOL. 188, NO. 1, (33-38), Online publication date: 1-Jul-2012.Lowrance W, Yee D, Savage C, Cronin A, O'Brien M, Donat S, Vickers A and Russo P (2018) Complications After Radical and Partial Nephrectomy as a Function of AgeJournal of Urology, VOL. 183, NO. 5, (1725-1730), Online publication date: 1-May-2010.Jeong I, Yoo C, Song K, Park J, Cho Y, Song C, Hong J, Ahn H and Kim C (2018) Age at Diagnosis is an Independent Predictor of Small Renal Cell Carcinoma Recurrence-Free SurvivalJournal of Urology, VOL. 182, NO. 2, (445-450), Online publication date: 1-Aug-2009.Related articlesJournal of Urology19 Aug 2008A Novel Technique for Creating Solid Renal Pseudotumors and Renal Vein-Inferior Vena Caval Pseudothrombus in a Porcine and Cadaveric Model Volume 180Issue 4October 2008Page: 1262-1266 Advertisement Copyright & Permissions© 2008 by American Urological AssociationKeywordsmortalityage groupscarcinomanephrectomykidneyrenal cellMetricsAuthor Information R. Houston Thompson Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Maria A. Ordonez State University of New York Downstate Medical School, New York, New York More articles by this author Alexia Iasonos Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Fernando P. Secin Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Bertrand Guillonneau Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Paul Russo Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Karim Touijer Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, New York More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract BACKGROUND The significance of adrenal invasion and tumor thrombus in renal cell carcinoma (RCC) has been debated recently. The authors evaluated the associations of direct adrenal invasion, perinephric fat invasion, and tumor thrombus level with outcome to determine whether reclassification would improve the prognostic accuracy of the current primary tumor classification. METHODS The authors studied 697 patients treated with nephrectomy for pT3 and pT4 RCC between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression and prognostic accuracy was measured using the c index. RESULTS Among patients with pT3 RCC, direct adrenal invasion was significantly associated with death from RCC (risk ratio, 2.11; P = 0.004). No significant difference in survival was found between patients with pT4 RCC and pT3 tumors with direct adrenal invasion ( P = 0.490). Among patients with pT3b RCC, those with level I–III tumor thrombus were significantly more likely to die of RCC compared with patients harboring level 0 tumor thrombus (risk ratio, 1.62; P &lt; 0.001). In addition, patients with fat invasion were more likely to die of RCC compared with pT3 patients without fat invasion (risk ratio, 1.87; P &lt; 0.001). Therefore, patients with pT3 RCC were reclassified into 4 prognostic groups, and this reclassification significantly improved prediction of death from RCC compared with the current classification ( c indices of 0.61 vs. 0.55, respectively). CONCLUSIONS Direct adrenal invasion from RCC should be reclassified as pT4. In addition, the proposed reclassification for patients with pT3 RCC improved prognostic accuracy. Cancer 2005;. © 2005 American Cancer Society.

Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor that can progress in the presence of an intact host immune system. We previously reported that survivin and B7-H1 are independently associated with disease progression and death when expressed by ccRCC tumors. Herein, we examine the clinical effect of ccRCC combined expression of both survivin and B7-H1.Specimens from 298 patients who underwent nephrectomy for ccRCC between 1990 and 1994 were immunohistochemically stained for survivin and B7-H1. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of both markers with ccRCC death were assessed using Cox proportional hazards regression models.At last follow-up, 94 patients died from ccRCC. Among the living patients, the median follow-up was 11.2 years (range, 0-15 years). There were 177 (59.4%) survivin(Low)/B7-H1(-), 51 (17.1%) survivin(Hi)/B7-H1(-), 29 (9.7%) survivin(Low)/B7-H1(+), and 41 (13.8%) survivin(Hi)/B7-H1(+) tumors. The 5-year cancer-specific survival rates for patients within each group were 89.3%, 59.7%, 70.0%, and 16.2%, respectively. Combined survivin(Hi)/B7-H1(+) expression was associated with ccRCC death univariately (risk ratio, 12.82; 95% confidence interval, 7.50-21.92; P < 0.001) and in multivariate analysis (risk ratio, 2.81; 95% confidence interval, 1.56-5.04; P < 0.001). Survivin(Hi)/B7-H1(+) tumors exhibited increased levels of infiltrating mononuclear cells and survivin-specific T cells compared with survivin(Low)/B7-H1(-) tumors.Patients with survivin(Hi)/B7-H1(+) ccRCC tumors are at increased risk of ccRCC death. Survivin(Hi)/B7-H1(+) tumors also harbor increased amounts of infiltrating mononuclear cells and survivin-specific T cells relative to survivin(Low)/B7-H1(-) tumors. Taken together, dual expression of survivin and B7-H1 can be used to predict ccRCC tumor aggressiveness.

Objective To characterize the incidence and clinicopathologic factors associated with late recurrence after surgical resection for renal cell carcinoma (RCC) because the recurrence patterns >5 years after nephrectomy have been poorly described. Methods We identified 1454 patients treated with nephrectomy for localized RCC from 1970 to 2000 who had remained free of disease for 5 years. Subsequent tumor recurrence was classified as renal recurrence and distant metastasis. The incidence of recurrence >5 years from surgery was estimated using the Kaplan-Meier method. The associations of clinicopathologic variables with late recurrence were analyzed using Cox proportional hazard regression models. Results With a median postoperative follow-up of 13.9 years (range 5.1-38.9), 63 patients (4.3%) experienced late renal recurrence at a median of 9.3 years (range 5.1-25.3), and 172 patients (11.8%) developed late distant metastases at a median of 9.6 years (range 5.1-26.6) after surgery. The estimated recurrence-free survival rate at 10 and 15 years was 97.3% and 95.2% for renal recurrence, and 93.1% and 85.9% for distant metastases, respectively. On multivariate analysis, increased tumor size (hazard ratio [HR] 1.12; P < .001) was associated with late renal tumor recurrence, and increased tumor size (HR 1.07; P = .018), clear cell or collecting duct histologic features (HR 3.76; P < .001), and tumor Stage pT1b (HR 2.8; P < .001), pT2a (HR 4.5; P < .001), pT2b (HR 3.4; P = .007), and pT3-pT4 (HR 5.1; P < .001) were associated with distant metastasis. Conclusion After an initial 5-year postoperative disease-free interval, approximately 5% and 15% of patients will develop renal recurrence and distant metastases, respectively, during the next decade. Therefore, long-term surveillance remains necessary after nephrectomy. To characterize the incidence and clinicopathologic factors associated with late recurrence after surgical resection for renal cell carcinoma (RCC) because the recurrence patterns >5 years after nephrectomy have been poorly described. We identified 1454 patients treated with nephrectomy for localized RCC from 1970 to 2000 who had remained free of disease for 5 years. Subsequent tumor recurrence was classified as renal recurrence and distant metastasis. The incidence of recurrence >5 years from surgery was estimated using the Kaplan-Meier method. The associations of clinicopathologic variables with late recurrence were analyzed using Cox proportional hazard regression models. With a median postoperative follow-up of 13.9 years (range 5.1-38.9), 63 patients (4.3%) experienced late renal recurrence at a median of 9.3 years (range 5.1-25.3), and 172 patients (11.8%) developed late distant metastases at a median of 9.6 years (range 5.1-26.6) after surgery. The estimated recurrence-free survival rate at 10 and 15 years was 97.3% and 95.2% for renal recurrence, and 93.1% and 85.9% for distant metastases, respectively. On multivariate analysis, increased tumor size (hazard ratio [HR] 1.12; P < .001) was associated with late renal tumor recurrence, and increased tumor size (HR 1.07; P = .018), clear cell or collecting duct histologic features (HR 3.76; P < .001), and tumor Stage pT1b (HR 2.8; P < .001), pT2a (HR 4.5; P < .001), pT2b (HR 3.4; P = .007), and pT3-pT4 (HR 5.1; P < .001) were associated with distant metastasis. After an initial 5-year postoperative disease-free interval, approximately 5% and 15% of patients will develop renal recurrence and distant metastases, respectively, during the next decade. Therefore, long-term surveillance remains necessary after nephrectomy.

No AccessJournal of UrologyAdult Urology1 Nov 2011Contemporary Trends in Nephrectomy for Renal Cell Carcinoma in the United States: Results From a Population Based Cohort Simon P. Kim, Nilay D. Shah, Christopher J. Weight, R. Houston Thompson, James P. Moriarty, Nathan D. Shippee, Brian A. Costello, Stephen A. Boorjian, and Bradley C. Leibovich Simon P. KimSimon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Nilay D. ShahNilay D. Shah Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota More articles by this author , Christopher J. WeightChristopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , James P. MoriartyJames P. Moriarty Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota More articles by this author , Nathan D. ShippeeNathan D. Shippee Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota More articles by this author , Brian A. CostelloBrian A. Costello Department of Oncology, Mayo Clinic, Rochester, Minnesota More articles by this author , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , and Bradley C. LeibovichBradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.07.041AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Despite benefits in functional renal outcome and the similar oncological efficacy of partial nephrectomy for renal cell carcinoma, previous studies show marked underuse of partial nephrectomy. We describe national trends in partial and radical nephrectomy using a contemporary, population based cohort. Materials and Methods: Using the 2003 to 2008 Nationwide Inpatient Sample we identified 188,702 patients treated with partial or radical nephrectomy for renal cell carcinoma at a total of 1,755 hospitals. Multivariate logistic regression was used to assess the independent associations of patient and hospital characteristics with partial nephrectomy. Post-estimations from multivariate logistic regression were done to ascertain the annual predicted probability of partial nephrectomy by hospital feature. Results: Overall 149,636 (79.3%) and 39,066 patients (20.7%) underwent radical and partial nephrectomy for renal cell carcinoma, respectively. Partial nephrectomy use increased each year from 16.8% in 2003 to 25.1% in 2008 (p for trend <0.001). On multivariate analysis patients were more likely to undergo partial nephrectomy at teaching (OR 1.31, p <0.001) and urban (OR 1.13, p = 0.05) hospitals compared to nonteaching and rural hospitals, respectively. Each quartile of higher nephrectomy annual volume was associated with higher odds of partial nephrectomy compared to the lowest quartile (OR 1.21, p <0.001). Although annual predicted partial nephrectomy use increased across all hospitals, differences in annual partial nephrectomy use by teaching status, site (urban vs rural) and case volume persisted with time. Conclusions: Although the use of partial nephrectomy for renal cell carcinoma is increasing nationally across all hospitals, academic and urban hospitals as well as those with higher nephrectomy volume continue to show higher partial nephrectomy use for renal cell carcinoma. References 1 : Cancer statistics, 2010. CA Cancer J Clin2010; 60: 277. 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Link, Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByLaguna M (2020) Re: Guideline Adherence for the Surgical Treatment of T1 Renal Tumours Correlates with Hospital Volume: An Analysis from the British Association of Urological Surgeons Nephrectomy AuditJournal of Urology, VOL. 204, NO. 3, (615-616), Online publication date: 1-Sep-2020.Laguna M (2020) Re: Impact of Hospital Nephrectomy Volume on Intermediate- to Long-Term Survival in Renal Cell CarcinomaJournal of Urology, VOL. 204, NO. 5, (1092-1093), Online publication date: 1-Nov-2020.Laguna M (2019) Re: Time Trends in Service Provision and Survival Outcomes for Patients with Renal Cancer Treated by Nephrectomy in England 2000-2010Journal of Urology, VOL. 201, NO. 5, (855-855), Online publication date: 1-May-2019.Laguna M (2017) Re: The Impact of Quality Variations on Patients Undergoing Surgery for Renal Cell Carcinoma: A National Cancer Database StudyJournal of Urology, VOL. 199, NO. 2, (338-339), Online publication date: 1-Feb-2018.Weinberg A, Wright J, Whalen M, Paulucci D, Woldu S, Berger S, Deibert C, Korets R, Hershman D, Neugut A and Badani K (2016) Use of Partial Nephrectomy after Acquisition of a Surgical Robot: A Population Based StudyUrology Practice, VOL. 3, NO. 6, (430-436), Online publication date: 1-Nov-2016.Kim S and Abouassaly R (2016) Treatment of Patients with Positive Margins after Partial NephrectomyJournal of Urology, VOL. 196, NO. 2, (301-302), Online publication date: 1-Aug-2016.Chughtai B, Scherr D, Del Pizzo J, Herman M, Barbieri C, Mao J, Isaacs A, Lee R, Te A, Kaplan S, Schlegel P and Sedrakyan A (2014) National Trends and Cost of Minimally Invasive Surgery in UrologyUrology Practice, VOL. 2, NO. 2, (49-54), Online publication date: 1-Mar-2015.Wang H, Abern M, Cost N, Chu D, Ross S, Wiener J and Routh J (2014) Use of Nephron Sparing Surgery and Impact on Survival in Children with Wilms Tumor: A SEER AnalysisJournal of Urology, VOL. 192, NO. 4, (1196-1202), Online publication date: 1-Oct-2014.Ghani K, Sukumar S, Sammon J, Rogers C, Trinh Q and Menon M (2013) Practice Patterns and Outcomes of Open and Minimally Invasive Partial Nephrectomy Since the Introduction of Robotic Partial Nephrectomy: Results from the Nationwide Inpatient SampleJournal of Urology, VOL. 191, NO. 4, (907-913), Online publication date: 1-Apr-2014.Patel H, Mullins J, Pierorazio P, Jayram G, Cohen J, Matlaga B and Allaf M (2012) Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial NephrectomyJournal of Urology, VOL. 189, NO. 4, (1229-1235), Online publication date: 1-Apr-2013.Abaza R and Prall D (2012) Drain Placement Can be Safely Omitted After the Majority of Robotic Partial NephrectomiesJournal of Urology, VOL. 189, NO. 3, (823-827), Online publication date: 1-Mar-2013.Simhan J, Canter D, Sterious S, Smaldone M, Tsai K, Li T, Viterbo R, Chen D, Greenberg R, Kutikov A and Uzzo R (2012) Pathological Concordance and Surgical Outcomes of Sporadic Synchronous Unilateral Multifocal Renal Masses Treated with Partial NephrectomyJournal of Urology, VOL. 189, NO. 1, (43-47), Online publication date: 1-Jan-2013.Kim S, Thompson R, Boorjian S, Weight C, Han L, Murad M, Shippee N, Erwin P, Costello B, Chow G and Leibovich B (2012) Comparative Effectiveness for Survival and Renal Function of Partial and Radical Nephrectomy for Localized Renal Tumors: A Systematic Review and Meta-AnalysisJournal of Urology, VOL. 188, NO. 1, (51-57), Online publication date: 1-Jul-2012.Simhan J, Smaldone M, Tsai K, Li T, Reyes J, Canter D, Kutikov A, Chen D, Greenberg R, Uzzo R and Viterbo R (2012) Perioperative Outcomes of Robotic and Open Partial Nephrectomy for Moderately and Highly Complex Renal LesionsJournal of Urology, VOL. 187, NO. 6, (2000-2004), Online publication date: 1-Jun-2012. Volume 186Issue 5November 2011Page: 1779-1785 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordstrendscarcinomarenal cellhospitalsnephrectomykidneyMetricsAuthor Information Simon P. Kim Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Nilay D. Shah Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota More articles by this author Christopher J. Weight Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author James P. Moriarty Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota More articles by this author Nathan D. Shippee Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota More articles by this author Brian A. Costello Department of Oncology, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Bradley C. Leibovich Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF DownloadLoading ...

No AccessJournal of UrologyAdult Urology1 May 2013Outcomes Following Radical Cystectomy for Nested Variant of Urothelial Carcinoma: A Matched Cohort Analysis Brian J. Linder, Igor Frank, John C. Cheville, R. Houston Thompson, Prabin Thapa, Robert F. Tarrell, and Stephen A. Boorjian Brian J. LinderBrian J. Linder Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Igor FrankIgor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , John C. ChevilleJohn C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Prabin ThapaPrabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , Robert F. TarrellRobert F. Tarrell Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author , and Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.11.006AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated oncological outcomes after radical cystectomy in patients with the nested variant of urothelial carcinoma and compared survival to that in patients with pure urothelial carcinoma of the bladder. Materials and Methods: We identified 52 patients with the nested variant who were treated with radical cystectomy between 1980 and 2004. Pathological specimens were re-reviewed by a single genitourinary pathologist. Patients were matched 1:2 by age, gender, ECOG (Eastern Cooperative Oncology Group) performance status, pathological tumor stage and nodal status to patients with pure urothelial carcinoma. Survival was estimated using the Kaplan-Meier method and compared with the log rank test. Results: Patients with the nested variant had a median age of 69.5 years (IQR 62, 74) and a median postoperative followup of 10.8 years (IQR 9.3, 11.2). Nested variant cancer was associated with a high rate of adverse pathological features since 36 patients (69%) had pT3–T4 disease and 10 (19%) had nodal invasion. Eight patients (15%) with nested variant cancer received perioperative chemotherapy. When patients with the nested variant were matched to a cohort with pure urothelial carcinoma, no significant differences were noted in 10-year local recurrence-free survival (83% vs 80%, p = 0.46) or 10-year cancer specific survival (41% vs 46%, p = 0.75). Conclusions: The nested variant of urothelial carcinoma is associated with a high rate of locally advanced disease at radical cystectomy. However, when stage matched to patients with pure urothelial carcinoma, patients with the nested variant did not have an increased rate of recurrence or adverse survival. Further studies are required to validate these findings and guide the optimal multimodal treatment approach to these patients. References 1 : Cancer statistics, 2012. CA Cancer J Clin2012; 62: 10. Google Scholar 2 : The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol2009; 27: 3. Google Scholar 3 : Unusual benign bladder tumor of Brunn nest origin. Urology1979; 14: 288. Google Scholar 4 : The nested variant of transitional cell carcinoma: a neoplasm resembling proliferation of Brunn's nests. Mod Pathol1992; 5: 240. Google Scholar 5 : Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases. Am J Surg Pathol1989; 13: 374. Google Scholar 6 : Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. Hum Pathol2010; 41: 163. Google Scholar 7 : The nested variant of transitional cell carcinoma: an aggressive neoplasm with innocuous histology. Mod Pathol1996; 9: 989. Google Scholar 8 : The nested variant of transitional cell carcinoma—a rare neoplasm with poor prognosis. Scand J Urol Nephrol2001; 35: 102. Google Scholar 9 : Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol2003; 16: 1289. Google Scholar 10 : AJCC Cancer Staging Handbook. New York: Springer2010. p xix. Google Scholar 11 : Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol2005; 23: 6533. Google Scholar 12 : Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol2010; 34: 1367. Google Scholar 13 : Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection. Urology2007; 70: 69. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLinder B, Boorjian S, Cheville J, Sukov W, Thapa P, Tarrell R and Frank I (2018) The Impact of Histological Reclassification during Pathology Re-Review—Evidence of a Will Rogers Effect in Bladder Cancer?Journal of Urology, VOL. 190, NO. 5, (1692-1697), Online publication date: 1-Nov-2013. Volume 189Issue 5May 2013Page: 1670-1675 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsurotheliumcystectomyurinary bladdermortalitycarcinomaMetricsAuthor Information Brian J. Linder Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Igor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author John C. Cheville Department of Pathology, Mayo Clinic, Rochester, Minnesota More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Prabin Thapa Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Robert F. Tarrell Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Expand All Advertisement PDF downloadLoading ...

Although partial nephrectomy (PN) has been associated with improved renal function compared with radical nephrectomy (RN) for renal cell carcinoma, the impact on overall survival (OS) remains controversial.To evaluate comparative OS and renal function in patients following PN and RN for a renal mass where malignancy was not a confounding factor.Using the Mayo Clinic Nephrectomy Registry, we retrospectively identified 442 patients with unilateral sporadic benign renal masses treated surgically with PN or RN between 1980 and 2008.The primary outcome measures were OS and the incidence of new-onset stage IV chronic kidney disease (CKD), determined using the Kaplan-Meier method. Cox models were used to test the association of nephrectomy type with these outcomes.Overall, 206 and 236 patients with benign renal masses were surgically treated with RN and PN, respectively. Patients who underwent RN were older (median age: 67 vs 64 yr; p=0.02) and had larger tumors (median size: 5.0 vs 2.7 cm; p<0.001). Median follow-up for patients still alive at last follow-up was 8.3 yr (range: 0.1-27.9 yr). Estimated OS (95% confidence interval [CI]) rates at 10 and 15 yr were 69% (62-76%) and 53% (45-62%) for RN compared with 80% (73-87%) and 74% (65-83%) following PN (p=0.032). After adjusting for covariates of interest, patients treated with RN were significantly more likely to die from any cause (hazard ratio [HR]: 1.75; 95% CI, 1.08-2.83; p=0.023) or develop stage IV CKD (HR: 4.23; 95% CI, 1.80-9.93; p<0.001) compared with patients who underwent PN. Limitations include the retrospective design, selection bias for surgical approach, and referral bias to a tertiary care facility.Our data suggest that PN may confer a clinical benefit for improved renal function and better OS compared with RN after excluding the confounding effect of malignancy.

We determined the clinical and pathological features associated with death from papillary renal cell carcinoma in 395 surgically treated patients.Papillary renal cell carcinoma tissue slides from each patient were reviewed for type (1 or 2), grade, TNM stage, coagulative tumor necrosis and sarcomatoid differentiation. Associations of clinical and pathological features with death from renal cell carcinoma were evaluated using Cox proportional hazards regression models and summarized by the HR and 95% CI. Cancer specific survival was estimated using the Kaplan-Meier method.Univariate analysis revealed that symptoms, tumor thrombus, tumor size, perinephric/renal sinus fat invasion, 2010 primary tumor classification, regional lymph node involvement, distant metastasis, 2010 TNM stage group, grade, tumor necrosis, sarcomatoid differentiation and papillary renal cell carcinoma type were associated with death from renal cell carcinoma. Grade was more strongly associated with death from renal cell carcinoma than papillary renal cell carcinoma type. Multivariate analysis indicated that symptoms, 2010 TNM stage group and grade jointly were significantly associated with death from renal cell carcinoma.This large series of patients with papillary renal cell carcinoma reveals features associated with death from renal cell carcinoma and confirms that grade is more predictive of outcome than papillary renal cell carcinoma type.

Purpose The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death. Patients and Methods We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (&lt; 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence. Results At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age. Conclusion We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation.

While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established. The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC). Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed. Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes. In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT (p = 0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p = 0.02), while receipt of postoperative BT was not (p = 0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0–15.7). Five-year RFS (p < 0.001) and CSS (p < 0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p = 0.001), cancer-specific mortality (HR: 1.55; p = 0.0001), and all-cause mortality (HR: 1.40; p < 0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death. Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality. In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality.

To describe the technical methods, safety, and local tumor control rate associated with percutaneous cryoablation of stage T1b renal cell carcinoma (RCC).A retrospective review of a percutaneous renal ablation registry was used to identify 46 patients with a total of 46 biopsy-proven RCC lesions measuring 4.1-7.0 cm treated with cryoablation between 2003 and 2011. The main outcome parameters investigated were adjunctive maneuvers, complications, and local tumor progression, and cancer-specific survival rates. Complication rates were categorized and recorded using the Clavien-Dindo classification system. Progression-free and cancer-specific survival rates were estimated using the Kaplan-Meier method.The mean treated RCC size was 4.8 cm (range, 4.1-6.4 cm). Prophylactic tumor embolization was performed in 7 patients (15%), ipsilateral ureteral stents were placed in 7 patients (15%), and hydrodisplacement of bowel was performed in the treatment of 16 tumors (35%). A single technical failure (2.2%) was observed at the time of ablation. Thirty-six tumors (78%) had follow-up imaging at 3 months or later following ablation, including a single recurrence at 9 months after ablation. The mean duration of follow-up for the 35 RCC tumors that did not recur was 2.0 years (range, 0.3-6.1 y). Estimated local progression-free survival rate at 3 years was 96.4%. Of the 46 cryoablation procedures, there were 7 complications (15.2%) of grade II or worse.The results suggest that cryoablation represents a valid treatment alternative for select patients with clinical stage T1b RCC. Complications are frequent enough that multidisciplinary patient management should be considered.

To identify tumor and patient-related risk factors for major complications following renal cryoablation and to develop a model for predicting these adverse events.Institutional review board approval and informed patient consent were obtained for this HIPAA-compliant retrospective study. All 398 renal cryoablation procedures performed from 2003 through 2011 were reviewed to identify tumor and patient-related risk factors associated with major complications (Clavien-Dindo classification, ≥ grade III). A scoring system for predicting these adverse events was then developed using risk factor weighting obtained from a multivariate logistic regression model. To internally validate this model, the scoring system was then applied to all 73 renal cryoablation procedures performed during 2012.Among tumor-related factors evaluated, Maximal tumor diameter (P = .0006) and Central tumor location (P = .02) were significantly associated with major complications. Among patient-related factors evaluated, prior Myocardial infarction (MI) (P = .002) and Complicated diabetes mellitus (P = .01) were significantly associated with major complications. This resulted in the (MC)2 risk scoring system, with (MC)2 risk score = 2.5 points (for tumors ≤ 2.5 cm in maximal diameter) or 0.1 points for each millimeter of maximal tumor diameter (for tumors > 2.5 cm) + 1.5 points (if central tumor location) + 2.5 points (if patient history of prior MI) + 3.0 points (if patient history of complicated diabetes). Mean (MC)2 risk score for all renal cryoablations was 4.7 (standard deviation, 1.9; range, 2.5-15.3). The observed major complication rates were 2.0% (95% confidence interval [CI]: 0.6%, 4.6%) in the low-risk group (score < 5.0), 12.8% (95% CI: 7.5%, 19.9%) in the moderate-risk group (score of 5.0-8.0), and 39.1% (95% CI: 19.7%, 61.5%) in the high-risk group (score > 8.0). Application of the (MC)2 scoring system to the validation group yielded a concordance index of 0.82 (95% CI: 0.62, 1.00).The results of this study suggest that the (MC)2 risk score is a valuable tool for predicting major complications in patients undergoing renal cryoablation. However, external validation is warranted.

It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC). The objective of this study was to determine whether nucleolar grading and the recently described chromophobe RCC grading system by Paner and colleagues provide prognostic information. Pathologic features of 185 patients with chromophobe RCC treated surgically between 1970 and 2006 were reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer-specific (CS) survival was estimated using the Kaplan-Meier method, and associations with CS survival were evaluated using Cox proportional hazard regression models. Twenty-three patients died from RCC at a mean of 3.0 years after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15 years after surgery. Univariate associations with CS survival included the 2010 TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis, chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features remained significantly associated with CS survival after adjusting for the 2010 TNM stage groupings. When the analysis was restricted to the 155 patients with nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping (I vs. II) was significantly associated with CS survival (P=0.03). Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed.

<h2>Abstract</h2> A subset of renal cell carcinomas shows TFEB overexpression secondary to <i>MALAT1-TFEB</i> gene fusion. As alternate mechanisms of TFEB overexpression are likely to have the same effect, we sought to determine the frequency of amplification of <i>TFEB</i> and the adjacent <i>VEGFA</i> gene at 6p21.1. As patients with metastatic renal cell carcinomas are managed with anti-VEGF therapies, we retrospectively assessed therapeutic response in patients with amplified tumors. Amplification status was analyzed for 875 renal cell carcinomas from our institution, a consultative case and 794 cases from The Cancer Genome Atlas. Cases were classified as having low level (5–10 copies), and high-level amplification (>10 copies), and were further analyzed for adjacent oncogene copy number status (<i>n</i>=6; 3 single-nucleotide polymorphism genomic microarray, 3 The Cancer Genome Atlas) and structural rearrangements (<i>n</i>=1; mate-pair sequencing). These were then reviewed for histopathology, immunophenotype, and response to VEGF-targeted therapy on follow-up. In all, 10/875 (1.1%) institutional cases, 1 consultative case, and 3/794 (0.4%) of The Cancer Genome Atlas cases showed <i>TFEB</i> high-level amplification, while 14/875 (1.6%) cases showed <i>TFEB</i> low-level amplification. All cases had associated <i>VEGFA</i> amplification. This was confirmed with evaluation for copy number changes (<i>n</i>=6). The 6p21.1 high and low-level amplified tumors occurred in adults (mean age: 66), with over half being ≥pT3 (13/25, 52%), and most showed oncocytic, tubulopapillary features and high grade (≥grade 3: 20/22, 91%). These were aggressive tumors with metastasis and death from renal cell carcinoma in 11 (of 24, 46%) cases. Four patients received targeted therapy and had a mean survival of 31 months (range: 17–50) post nephrectomy. In summary, a group of aggressive renal cell carcinomas show genomic amplification of the 6p21.1 region including <i>TFEB</i> and <i>VEGFA</i> genes and share morphologic features. Additional studies are warranted to determine whether these patients respond to anti-VEGF therapy.

Objective To demonstrate sarcomatoid differentiation is an independent prognostic feature for patients with grade 4 renal cell carcinoma ( RCC ) with or without distant metastases. To identify independent predictors of survival, evaluate the correlation between the amount of sarcomatoid differentiation and cancer‐specific survival ( CSS ), and to design a multivariate prognostic model for patients with sarcomatoid RCC . Patients and Methods We used the Mayo Clinic Nephrectomy Registry to identify 204 post‐nephrectomy patients with sarcomatoid‐variant RCC , as well as 207 patients with unilateral grade 4 RCC without sarcomatoid features for comparison. All slides were reviewed by one pathologist. CSS was estimated using the K aplan– M eier method. The associations of clinical and pathological features with death from RCC were evaluated using Cox proportional hazards regression models. Results For all patients with grade 4 RCC , the presence of sarcomatoid differentiation was associated with a 58% increased risk of death from RCC ( P &lt; 0.001). For patients with grade 4 non‐metastatic ( M0 ) RCC , the presence of sarcomatoid differentiation was associated with an 82% increased risk of death from RCC ( P &lt; 0.001). For patients with sarcomatoid RCC , the 2009 primary tumour classifications, presence of regional lymph nodes and distant metastases, coagulative tumour necrosis, and the amount of sarcomatoid differentiation were each significantly associated with death from RCC in a multivariate setting. After adjusting for other prognostic variables, each 10% increase in the amount of sarcomatoid differentiation was associated with a 6% increased risk of death from RCC ( P = 0.028). Patients whose tumours contained ≥30% (median amount) sarcomatoid differentiation were 52% more likely to die from RCC compared with patients whose tumours contained &lt;30% sarcomatoid differentiation (hazard ratio 1.52; P = 0.018). Conclusions Among patients with grade 4 RCC , either with or without distant metastases at surgery, sarcomatoid differentiation is significantly associated with adverse survival in a multivariate setting. We also suggest for the first time that the percentage of sarcomatoid differentiation is an independent prognostic feature in a multivariate setting. The 2009 primary tumour classifications, regional lymph node status, the presence of distant metastases classifications, coagulative tumour necrosis, and the amount of sarcomatoid differentiation are independent predictors of survival for patients with sarcomatoid RCC .

To evaluate the clinical and radiographic predictors of the need for partial or circumferential resection of the inferior vena cava (IVC) requiring complex vascular reconstruction during venous tumour thrombectomy for renal cell carcinoma (RCC).Data were collected on 172 patients with RCC and IVC (levels I-IV) venous tumour thrombus who underwent radical nephrectomy with tumour thrombectomy at the Mayo Clinic between 2000 and 2010. Preoperative imaging was re-reviewed by one of two radiologists blinded to details of the patient's surgical procedure. Univariable and multivariable associations of clinical and radiographic features with IVC resection were evaluated by logistic regression. A secondary analysis was used to assess the ability of the model to predict histological invasion of the IVC by the tumour thrombus.Of the 172 patients, 38 (22%) underwent IVC resection procedures during nephrectomy. Optimum radiographic thresholds were determined to predict the need for IVC resection based on preoperative imaging included a renal vein diameter at the renal vein ostium (RVo) of 15.5 mm, maximum anterior-posterior (AP) diameter of the IVC of 34.0 mm and AP and coronal diameters of the IVC at the RVo of 24 and 19 mm, respectively. On multivariable analysis, the presence of a right-sided tumour (odds ratio 3.3; P = 0.017), an AP diameter of the IVC at the RVo of ≥24.0 mm (odds ratio 4.4; P = 0.017), and radiographic identification of complete occlusion of the IVC at the RVo (odds ratio 4.9; P < 0.001) were associated with a significantly increased risk of IVC resection. The c-index for the model was 0.81.We present a multivariable model of the radiographic features associated with the need for IVC resection during tumour thrombectomy. Pending external validation, this model may be used for preoperative planning, patient counselling and planned involvement of vascular surgical colleagues in anticipation of the need for complex vascular repair.

Renal cell carcinoma (RCC) with isolated lymph node (LN) involvement has historically been associated with poor prognosis. However, a subset of patients may experience long-term survival.To examine the natural history of RCC with isolated LN involvement following surgical resection with long-term follow-up, and to evaluate clinicopathologic features associated with disease progression and survival.A total of 138 patients with isolated pN1M0 RCC underwent partial or radical nephrectomy and LN dissection from 1980 to 2010.Partial or radical nephrectomy with LN dissection.Metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between clinicopathologic features and oncologic outcomes were evaluated using Cox regression models.Median follow-up among survivors was 8.5 yr. The 5-yr and 10-yr MFS, CSS, and OS rates were 16% and 15%, 26% and 21%, and 25% and 15%, respectively. The median time to development of metastases was only 4.2 mo. On multivariable analysis, symptoms at presentation (hazard ratio [HR] 2.40; p=0.03), inferior vena cava tumor thrombus (HR 1.99; p=0.003), clear cell (HR 2.21; p=0.01) and collecting duct/not otherwise specified (HR 4.28; p<0.001) histologic subtypes, pT4 stage (HR 2.64; p=0.005), and coagulative tumor necrosis (HR 2.51; p<0.001) were independently associated with development of metastases. MFS rates at 1 yr after surgery were 71%, 63%, 33%, and 7% for patients with one, two, three, and four to five adverse features, respectively. Limitations include surgical selection bias.Although isolated pN1 disease portends a poor prognosis, a small subset of patients experience durable long-term survival after surgical resection of isolated lymphatic metastases. Adverse prognostic features may enhance patient risk stratification and facilitate multimodal management approaches.Although isolated lymph node metastases portend a poor prognosis, a small subset of patients experience long-term survival following surgical resection.

Micropapillary urothelial carcinoma exhibits amplification of the human epidermal growth factor receptor, ERBB2(HER2), and overexpression of the ERBB2 protein product. The clinical significance of this has yet to be established. The objective of this study was to examine ERBB2 amplification and protein expression in micropapillary urothelial carcinoma and stage-matched typical urothelial carcinoma treated by radical cystectomy to assess the frequency of amplification and protein expression, and to determine the association with cancer-specific survival. Pathologic material and data from patients undergoing cystectomy at Mayo Clinic between 1980 and 2008 were reviewed. ERBB2 amplification by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry were assessed. Univariate and multivariate Cox proportional hazards regression models were used to evaluate for associations of ERBB2 amplification and protein expression with survival. ERBB2 amplification was identified in 9 (15%) of 61 micropapillary carcinomas compared with 9 (9%) of 100 urothelial carcinomas. In patients with micropapillary carcinoma, ERBB2 amplification was associated with a nearly threefold increased risk of cancer death. ERBB2 amplification (hazard ratio 4.3; P=0.0008) remained associated with an increased risk of death from bladder cancer among patients with micropapillary urothelial carcinoma on multivariate analysis. The association of cancer-specific survival and ERBB2 amplification was not seen in patients with urothelial carcinoma. ERBB2 immunohistochemistry correlated with ERBB2 amplification but there was no association of ERBB2 protein expression and survival. ERBB2 amplification is more frequent in micropapillary urothelial carcinoma than typical urothelial carcinoma, and patients with micropapillary carcinoma who have ERBB2 amplification have worse cancer-specific survival than those who do not. Identification of ERBB2 amplification in micropapillary carcinoma could provide important prognostic information and possibly provide a role for ERBB2 targeted therapy.

Determining clinicopathologic features that stratify the risk of disease progression in patients with seminal vesicle invasion at radical prostatectomy remains critical for patient counseling, clinical trial enrollment, and the judicious application of secondary therapies. Then, we evaluated the prognostic significance of concomitant extracapsular extension (ECE) in patients with seminal vesicle invasion and negative lymph nodes at radical prostatectomy.We identified 1,132 patients who underwent prostatectomy between 1987 and 2009 and were found to have pT3bN0 disease. Median postoperative follow-up was 10.6 years (interquartile range, 5.9-15.3). Survival was estimated using the Kaplan-Meier method and compared for patients with and without ECE with the log-rank test. The association of ECE with outcome was evaluated using Cox proportional hazards regression models.A total of 693 (61%) patients were noted to have ECE. Compared with pT3bN0 patients without ECE, patients with pT3bN0 tumors and ECE had a significantly worse 15-year biochemical recurrence-free survival (29% vs. 39%; P<0.001), systemic progression-free survival (71% vs. 81%; P<0.001), cancer-specific survival (80% vs. 89%; P<0.001), and overall survival (50% vs. 63%; P<0.001). On multivariate analysis, the presence of ECE was associated with significantly increased risks of systemic progression (hazard ratio [HR], 1.56; P=0.006), death from prostate cancer (HR, 1.71; P=0.01), and all-cause mortality (HR, 1.35; P=0.007). Meanwhile, adjuvant hormonal therapy, which was received by 334 patients (29.5%), was associated with significantly decreased risks of systemic progression (HR, 0.50; P=0.0004) and cancer death (HR, 0.57; P=0.03), but not all-cause mortality (HR, 0.81; P=0.09). Limitations included retrospective design and nonstandardized application of secondary treatments.The presence of ECE in patients with pT3bN0 prostate cancer is associated with increased risks of systemic progression and cancer death. Pending validation, ECE may be incorporated into risk stratification or staging classification or both. Meanwhile, these patients continue to represent ideal candidates for adjuvant therapy trials.

While multiple independent clinicopathological variables are associated with the outcome of radical cystectomy for bladder cancer, limited prediction tools exist to facilitate individualized risk assessment. We developed the SPARC (Survival Prediction After Radical Cystectomy) score, a prediction model for bladder cancer specific survival after radical cystectomy.We evaluated 2,403 patients who underwent radical cystectomy without neoadjuvant therapy at our institution between 1980 and 2008 with pathological re-review of all specimens. Of these patients 1,776 with nonmetastatic urothelial carcinoma were identified for analysis. A multivariate model was developed using stepwise selection to determine variables associated with cancer specific survival. We created a scoring system based on the β coefficients of this model.Median followup after radical cystectomy in patients alive at last followup was 10.5 years (IQR 7.3, 15.3), during which time 610 had died of bladder cancer. In addition to pathological tumor stage, nodal status, multifocality and lymphovascular invasion, the patient specific factors of Charlson comorbidity index, Eastern Cooperative Oncology Group (ECOG) performance status, current smoking, preoperative hydronephrosis and receipt of adjuvant chemotherapy were significantly associated with the risk of bladder cancer death. We used cumulative scores of these variables to stratify patients into risk groups with 95%, 80%, 60%, 38% and 23% 5-year cancer specific survival from the lowest to the highest risk group, respectively (p<0.0001). The concordance index of this model was 0.75.We present a model to individualize the estimation of cancer specific survival after radical cystectomy. Pending external validation, these data may be used for patient counseling, specifically in regard to recommendations for adjuvant therapy and surveillance frequency, as well as for clinical trial development.

There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer.This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer.A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL.Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes.Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers.

The optimal sequence of cytoreductive nephrectomy and targeted therapy of metastatic renal cell carcinoma is unclear. We compared overall survival between patients with metastatic renal cell carcinoma treated with initial cytoreductive nephrectomy with or without subsequent targeted therapy vs initial targeted therapy with or without subsequent cytoreductive nephrectomy.We evaluated the records of cases in the National Cancer Database diagnosed with metastatic renal cell carcinoma between 2006 and 2013 who were treated with cytoreductive nephrectomy and/or targeted therapy. Receipt of targeted therapy after initial cytoreductive nephrectomy and cytoreductive nephrectomy after initial targeted therapy were evaluated on competing risks analyses. To account for treatment selection bias, inverse probability of treatment weighting was performed based on the propensity to receive initial cytoreductive nephrectomy or initial targeted therapy. Overall survival was compared between the groups by Kaplan-Meier analysis and Cox proportional hazards regression.Of the 15,068 patients included in study 6,731 underwent initial cytoreductive nephrectomy and 8,337 received initial targeted therapy. Six months after initial cytoreductive nephrectomy 48.0% of patients received targeted therapy, of whom 15.3% died after initial cytoreductive nephrectomy prior to targeted therapy. Six months after initial targeted therapy 4.7% of patients underwent cytoreductive nephrectomy, of whom 44.9% died after initial targeted therapy prior to cytoreductive nephrectomy. Initial cytoreductive nephrectomy (OR 2.02, 95% CI 1.69-2.43, p <0.001) and cytoreductive nephrectomy after initial targeted therapy (HR 2.6, 95% CI 1.69-4.01, p <0.001) were more likely to be performed at academic vs community institutions. On inverse probability of treatment weighting analysis initial cytoreductive nephrectomy was associated with improved overall survival compared to initial targeted therapy (median 16.5 vs 9.2 months, HR 0.61, 95% CI 0.59-0.64, p <0.001).Given the greater likelihood of receiving multimodal therapy and the associated overall survival benefit, these data support cytoreductive nephrectomy as the initial approach to metastatic renal cell carcinoma in appropriate surgical candidates. Continued efforts are warranted to establish the optimal multimodal approach in these patients.

Nephron-sparing surgery is the preferred surgical management of cT1 renal masses, but observational and randomized data conflict regarding a survival benefit. To examine the associations of radical nephrectomy (RN) versus partial nephrectomy (PN) with oncologic and nononcologic outcomes. A total of 2459 adults were treated with RN or PN between 1990 and 2011 for a unilateral, sporadic, cT1, M0 solid renal mass. RN or PN. Associations of the type of nephrectomy with oncologic outcomes (local ipsilateral recurrence, distant metastases, and cancer-specific mortality [CSM]) and nononcologic outcomes (other-cause mortality [OCM], all-cause mortality [ACM], ≥10% decrease in estimated glomerular filtration rate [CKD10%], and decrease in estimated glomerular filtration rate to <45 ml/min/1.73 m2 [CKD < 45]) were evaluated using several propensity score (PS) techniques. After PS adjustment using preoperative features, RN was associated with an increased risk of distant metastases, CSM, ACM, CKD10%, and CKD < 45, but not with OCM. However, there remained imbalance in pathologic features. We therefore repeated these analyses in the subset of 1609 patients with renal cell carcinoma (RCC). After adjusting for both preoperative and pathologic features, there was no significant difference in the development of distant metastases or CSM. Although RN remained associated with an increased risk of CKD10% (hazard ratio [HR] 2.07–2.21; p < 0.001 for each PS technique) and CKD < 45 (HR 2.70–2.99; p < 0.001 for each PS technique), it was not significantly associated with OCM (HR 1.10–1.17; p = 0.08–0.5 for each PS technique) or ACM (HR 1.14–1.15; p = 0.2–0.3 for each PS technique, except HR 1.18; p = 0.03 by inverse probability weights). Limitations include unmeasured confounding. Although RN was associated with an increased risk of chronic kidney disease compared with PN, it was not associated with a statistically significant difference in CSM or ACM among patients with cT1 RCC. This study suggests that partial nephrectomy is not associated with markedly improved survival compared with radical nephrectomy.

Mutations of the succinate dehydrogenase (SDHX) enzyme subunits commonly lead to a loss of function of the holoenzyme complex, and germline SDHX mutations lead to a genetic predisposition to SDH-deficient neoplasms, including renal cell carcinomas (RCC). Similarly, loss-of-function alterations of fumarate hydratase (FH) leads to a genetic predisposition to hereditary leiomyomatosis and renal cell cancer (HLRCC)–associated RCC. Loss of FH leads to an accumulation of fumarate and aberrantly high levels of S-(2-succino)-cysteine (2SC). Subtype-specific consecutively diagnosed renal cell neoplasms were selected for the study and cases were not otherwise selected based on clinicopathologic features. Tissue microarrays were constructed from 1009 renal cell neoplasms (papillary: 400, clear cell: 203, chromophobe: 87, oncocytomas [original diagnosis]: 273, unclassified: 46) and these cases were immunostained for SDHA/SDHB to screen for SDH loss. A smaller subset (n = 730; oncocytomas, papillary and unclassified RCCs) were screened for FH-deficiency using immunohistochemistry for FH/2SC. Loss of SDHA/SDHB was seen in three of 273 tumors originally diagnosed as oncocytomas (1.1%). Diffuse nuclear and cytoplasmic 2SC staining, with retained FH expression was seen in one case (suggestive of dysfunctional FH protein), while absent FH was seen in 3 cases (2/400 papillary RCCs, 0.5% and 2/46 unclassified RCCs, 4.35%). No aberrant FH/2SC expression was noted in 273 cases originally diagnosed as oncocytomas. SDH-deficient RCCs were identified only in the cases originally diagnosed as oncocytomas (1.1%), while FH-deficient RCCs were identified in the papillary (0.5%) and unclassified RCC cohorts (4.35%). These results can help guide immunohistochemistry-based screening strategies for these tumors.

It is uncertain whether lymph node dissection (LND) provides a therapeutic benefit in renal cell carcinoma (RCC). To evaluate the association of LND with oncologic outcomes among patients undergoing radical nephrectomy (RN) for nonmetastatic RCC. A retrospective cohort study of 1797 patients treated with RN for M0 RCC between 1990 and 2010, including 606 (34%) who underwent LND. RN with or without LND. The associations of LND with the development of distant metastases, cancer-specific mortality (CSM), and all-cause mortality (ACM) were evaluated using 1:1 propensity score (PS) matching, adjustment for/stratification by PS quintile, and inverse probability weighting. Cox models were used to evaluate the association of the number of lymph nodes removed with oncologic outcomes. A total of 111 (6.2%) patients were pN1. The median follow-up after surgery was 10.6 yr. Following PS adjustment, there were no significant differences in clinicopathologic features between patients with and without LND. In the overall cohort, LND was not significantly associated with a reduced risk of distant metastases, CSM, or ACM. Moreover, LND was not associated with improved oncologic outcomes even among patients at increased risk of pN1 disease, including those with preoperative radiographic lymphadenopathy, or across increasing threshold probabilities for pN1 disease from 0.05 to 0.50. Among patients who underwent LND, the extent of LND was not significantly associated with the development of distant metastases, CSM, or ACM. Limitations include the retrospective design. We did not identify an oncologic benefit to LND in the overall cohort or among patients at increased risk of nodal disease. These findings do not support a therapeutic benefit to LND in patients with M0 RCC. Lymph node dissection does not appear to provide a therapeutic benefit in patients with nonmetastatic renal cell carcinoma.

Intratumor molecular heterogeneity has been reported for primary clear cell renal cell carcinoma (ccRCC) tumors; however, heterogeneity in metastatic ccRCC tumors has not been explored. To evaluate intra- and intertumor molecular heterogeneity in resected metastatic ccRCC tumors. We identified 111 patients who had tissue available from their primary tumor and at least one metastasis. ClearCode34 genes were analyzed for all tumors. Primary and metastatic tumors were classified as clear cell type A (ccA) or B (ccB) subtypes. Logistic and Cox regression were used to evaluate associations with pathologic features and survival. Intratumor heterogeneity of ccA/ccB subtypes was observed in 22% (95% confidence interval [CI] 3–60%) of metastatic tumors. Subtype differed across longitudinal metastatic tumors from the same patient in 23% (95% CI 10–42%) of patients and across patient-matched primary and metastatic tumors in 43% (95% CI 32–55%) of patients. Association of subtype with survival was validated in primary ccRCC tumors. The ccA/ccB subtype in metastatic tumors was significantly associated with metastatic tumor location, metastatic tumor grade, and presence of tumor necrosis. A limitation of this study is that we only analyzed patients who had both a nephrectomy and metastasectomy. Approximately one quarter of metastatic tumors displayed intratumor heterogeneity; a similar rate of heterogeneity was observed across longitudinal metastatic tumors. Thus, for biomarker studies it is likely adequate to analyze a single sample per metastatic tumor provided that pathologic review is incorporated into the study design. Subtypes across patient-matched primary and metastatic tumors differed 43% of the time, suggesting that the primary tumor is not a good surrogate for the metastatic tumor. Primary and secondary/metastatic cancers of the kidney differed in nearly one half of ccRCC patients. The pattern of this relationship may affect tumor growth and the most suitable treatment.

Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC).To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients.The study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2-T4N0M0 bladder cancer.Descriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses.The median TTC was 7.57wk (interquartile range 5.2-10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of <1 (p=0.027). The group with TTC >10wk had significantly lower OM-free (p=0.003) and CSM-free rates (p<0.001) than the group with TTC ≤10wk. TTC was independently associated with higher risk of OM (p=0.027) and CSM (p=0.004) after accounting for age, gender, pathologic extravesical disease, and nodal status.TTC of >10wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC.The impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

Amplifications of JAK2, PD-L1, and PD-L2 at 9p24.1 lead to constitutive expression of PD-L1. This, coupled with JAK2-activation dependent upregulation of PD-L1 and adaptive/induced expression leads to higher tumor PD-L1 expression and immune evasion. Renal tumors were therefore evaluated for 9p24.1 amplifications. A combination of next generation sequencing-based copy number analysis, fluorescence in situ hybridization for JAK2/INSL6 and PD-L1/PD-L2 and immunohistochemistry for phospho-STAT3 (downstream target of JAK2), PD-L1, PD-L2, and PD-1 was performed. In this study we interrogated a “Discovery” cohort of 593 renal tumors, a “Validation” cohort of 398 high-grade renal tumors, The Cancer Genome Atlas (879 cases) and other public datasets (846 cases). 9p24.1 amplifications were significantly enriched in renal tumors with sarcomatoid transformation (5.95%, 15/252) when compared to all histologic subtypes in the combined “Discovery”, “Validation” and public datasets (16/2636, 0.6%, p < 0.00001). Specifically, 9p24.1 amplifications amongst sarcomatoid tumors in public datasets, the “Discovery” and “Validation” cohorts were 7.7% (6/92), 15.1% (5/33), and 3.1% (4/127), respectively. Herein, we describe 13 cases and amplification status for these was characterized using next generation sequencing (n = 9) and/or fluorescence in situ hybridization (n = 10). Correlation with PD-L1 immunohistochemistry (n = 10) revealed constitutive expression (mean H-score: 222/300, n = 10). Analysis of outcomes based on PD-L1 expression in tumor cells performed on 282 cases (“Validation” cohort) did not reveal a significant prognostic effect and was likely reflective of advanced disease. A high incidence of constitutive PD-L1 expression in tumor cells in the “Validation” cohort (H-Score ≥250/300) was noted amongst 83 rhabdoid (6%) and 127 sarcomatoid renal tumors (7.1%). This suggests additional mechanisms of constitutive expression other than amplification events. Importantly, two patients with 9p24.1-amplified sarcomatoid renal tumors showed significant response to immunotherapy. In summary, a subset of renal tumors with sarcomatoid transformation exhibits constitutive PD-L1 overexpression and these patients should be evaluated for enhanced response to immunotherapy.

Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability.We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models.Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001).Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.

<h2>Abstract</h2><h3>Objective</h3> To study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC). <h3>Patients and Methods</h3> The Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML). <h3>Results</h3> A total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of <i>TP53</i>, <i>RB1</i>, and <i>ATRX</i>. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm. <h3>Conclusion</h3> The identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.

No AccessJournal of UrologyAdult Urology1 Sep 2021The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-AnalysisThis article is commented on by the following:Editorial Comment Vidit Sharma, Tanner S. Miest, Tristan S. Juvet, Amir Toussi, Vignesh Packiam, Karim Chamie, Surena F. Matin, Stephen A. Boorjian, R. Houston Thompson, Igor Frank, Matthew K. Tollefson, and Aaron M. Potretzke Vidit SharmaVidit Sharma Department of Urology, Mayo Clinic, Rochester, Minnesota Department of Urology, University of California, Los Angeles, California Greater Los Angeles VA, Health Services Research and Development Program, Los Angeles, California Financial and/or other relationship with Cold Genesys. More articles by this author , Tanner S. MiestTanner S. Miest Department of Urology, MD Anderson Cancer Center, Houston, Texas More articles by this author , Tristan S. JuvetTristan S. Juvet Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Amir ToussiAmir Toussi Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania More articles by this author , Vignesh PackiamVignesh Packiam Department of Urology, University of Iowa Medical Center, Iowa City, Iowa More articles by this author , Karim ChamieKarim Chamie Department of Urology, University of California, Los Angeles, California More articles by this author , Surena F. MatinSurena F. Matin Department of Urology, MD Anderson Cancer Center, Houston, Texas Financial and/or other relationship with Urogen and Ology Education. More articles by this author , Stephen A. BoorjianStephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota Financial and/or other relationship with Ferring, ArTara and FerGene. More articles by this author , R. Houston ThompsonR. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Igor FrankIgor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , Matthew K. TollefsonMatthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author , and Aaron M. PotretzkeAaron M. Potretzke §Correspondence: Department of Urology, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905 telephone: 507-284-3983; FAX: 507-284-4951; E-mail Address: [email protected] Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001834AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. Materials and Methods: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. Results: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). Conclusions: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences. References 1. : Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas on oncological outcomes: a meta-analysis. BJU Int 2018; 121: 184. Google Scholar 2. : Diagnostic ureteroscopy prior to radical nephroureterectomy for upper tract urothelial carcinoma increased the risk of intravesical recurrence. Urol Int 2018; 100: 92. 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Google Scholar 12. : Risk of intravesical recurrence after ureteroscopic biopsy for upper tract urothelial carcinoma: does the location matter?J Endourol 2017; 31: 259. Google Scholar 13. : Predictors for intravesical recurrence following radical nephroureterectomy for upper tract urothelial carcinoma: a national multicenter analysis. Clin Genitourin Cancer 2017; 15: e1055. Google Scholar 14. : Impact of diagnostic ureteroscopy before radical nephroureterectomy on intravesical recurrence in patients with upper tract urothelial cancer. Investig Clin Urol 2020; 61: 158. Google Scholar 15. : Diagnostic ureteroscopy prior to nephroureterectomy for urothelial carcinoma is associated with a high risk of bladder recurrence despite technical precautions to avoid tumor spillage. World J Urol 2020; 38: 159. Google Scholar 16. : Is ureteroscopy needed prior to nephroureterectomy? An evidence-based algorithmic approach. Urology 2016; 88: 43. Google Scholar 17. : Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2020; 18: 329. Google Scholar 18. : European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol 2021; 79: 62. Google Scholar 19. : Intravesical irrigation might prevent bladder recurrence in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma. Int J Urol 2019; 26: 791. Google Scholar 20. : Percutaneous image-guided core needle biopsy for upper tract urothelial carcinoma. Urology 2020; 135: 95. Google Scholar 21. : Safety and diagnostic accuracy of percutaneous biopsy in upper tract urothelial carcinoma. BJU Int 2015; 115: 625. Google Scholar 22. : High rate of pathologic upgrading at nephroureterectomy for upper tract urothelial carcinoma. Urology 2012; 79: 615. Google Scholar 23. : Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management. Urology 2011; 78: 82. Google Scholar 24. : Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: are they clonally related? A systematic review. Urol Oncol 2020; 38: 590. Google Scholar 25. : Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience. BJU Int 2012; 110: 1608. Google Scholar 26. : Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol 2013; 31: 1422. Google Scholar 27. : British Association of Urological Surgeons Section of Oncology. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol 2011; 60: 703. Google Scholar 28. : A systematic review and meta-analysis of clinicopathologic factors linked to intravesical recurrence after radical nephroureterectomy to treat upper tract urothelial carcinoma. Eur Urol 2015; 67: 1122. Google Scholar 29. : Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy. BJU Int 2014; 114: 56. Google Scholar 30. : Clonal relatedness and mutational differences between upper tract and bladder urothelial carcinoma. Clin Cancer Res 2019; 25: 967. Google Scholar © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited BySong Y, Du Y, Qin C and Xu T (2022) The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis. Letter.Journal of Urology, VOL. 207, NO. 4, (937-937), Online publication date: 1-Apr-2022.Miest T and Matin S (2021) Editorial CommentJournal of Urology, VOL. 206, NO. 3, (576-576), Online publication date: 1-Sep-2021.Sharma V, Miest T, Chamie K, Matin S, Boorjian S and Potretzke A (2021) The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-analysis. Reply.Journal of Urology, VOL. 206, NO. 4, (1072-1072), Online publication date: 1-Oct-2021.Ghoreifi A, Douglawi A and Djaladat H (2021) The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-analysis. Letter.Journal of Urology, VOL. 206, NO. 4, (1071-1071), Online publication date: 1-Oct-2021.Related articlesJournal of UrologyJun 14, 2021, 12:00:00 AMEditorial Comment Volume 206Issue 3September 2021Page: 558-567Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordsurinary bladder neoplasmsrecurrenceureteroscopycarcinoma, transitional cellureteral neoplasmsAcknowledgmentsWe would like to acknowledge the Veterans Administration Health Services Research and Development Fellowship for its support of Vidit Sharma.MetricsAuthor Information Vidit Sharma Department of Urology, Mayo Clinic, Rochester, Minnesota Department of Urology, University of California, Los Angeles, California Greater Los Angeles VA, Health Services Research and Development Program, Los Angeles, California Financial and/or other relationship with Cold Genesys. More articles by this author Tanner S. Miest Department of Urology, MD Anderson Cancer Center, Houston, Texas More articles by this author Tristan S. Juvet Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Amir Toussi Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania More articles by this author Vignesh Packiam Department of Urology, University of Iowa Medical Center, Iowa City, Iowa More articles by this author Karim Chamie Department of Urology, University of California, Los Angeles, California More articles by this author Surena F. Matin Department of Urology, MD Anderson Cancer Center, Houston, Texas Financial and/or other relationship with Urogen and Ology Education. More articles by this author Stephen A. Boorjian Department of Urology, Mayo Clinic, Rochester, Minnesota Financial and/or other relationship with Ferring, ArTara and FerGene. More articles by this author R. Houston Thompson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Igor Frank Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Matthew K. Tollefson Department of Urology, Mayo Clinic, Rochester, Minnesota More articles by this author Aaron M. Potretzke Department of Urology, Mayo Clinic, Rochester, Minnesota §Correspondence: Department of Urology, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905 telephone: 507-284-3983; FAX: 507-284-4951; E-mail Address: [email protected] More articles by this author Expand All Advertisement PDF DownloadLoading ...

Personalized treatment for clinical T1 renal cortical masses (RCMs) should take into account competing risks related to tumor and patient characteristics.To develop treatment-specific prediction models for cancer-specific mortality (CSM), other-cause mortality (OCM), and 90-d Clavien grade ≥3 complications across radical nephrectomy (RN), partial nephrectomy (PN), thermal ablation (TA), and active surveillance (AS).Pretreatment clinical and radiological features were collected for consecutive adult patients treated with initial RN, PN, TA, or AS for RCMs at four high-volume referral centers (2000-2019).Prediction models used competing-risks regression for CSM and OCM and logistic regression for 90-d Clavien grade ≥3 complications. Performance was assessed using bootstrap validation.The cohort comprised 5300 patients treated with RN (n = 1277), PN (n = 2967), TA (n = 476), or AS (n = 580). Over median follow-up of 5.2 yr (interquartile range 2.5-8.7), there were 117 CSM, 607 OCM, and 198 complication events. The C index for the predictive models was 0.80 for CSM, 0.77 for OCM, and 0.64 for complications. Predictions from the fitted models are provided in an online calculator (https://small-renal-mass-risk-calculator.fredhutch.org). To illustrate, a hypothetical 74-yr-old male with a 4.5-cm RCM, body mass index of 32 kg/m2, estimated glomerular filtration rate of 50 ml/min, Eastern Cooperative Oncology Group performance status of 3, and Charlson comorbidity index of 3 has predicted 5-yr CSM of 2.9-5.6% across treatments, but 5-yr OCM of 29% and risk of 90-d Clavien grade 3-5 complications of 1.9% for RN, 5.8% for PN, and 3.6% for TA. Limitations include selection bias, heterogeneity in practice across treatment sites and the study time period, and lack of control for surgeon/hospital volume.We present a risk calculator incorporating pretreatment features to estimate treatment-specific competing risks of mortality and complications for use during shared decision-making and personalized treatment selection for RCMs.We present a risk calculator that generates personalized estimates of the risks of death from cancer or other causes and of complications for surgical, ablation, and surveillance treatment options for patients with stage 1 kidney tumors.

Significance Statement Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex. Background Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. Methods We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel–Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR &lt;10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria). Results Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis. Conclusions Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD.

Immune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration–approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited. To evaluate the safety and outcomes of nephrectomy following an ICI. A retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021. Clinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method. A total of 113 patients with a median (interquartile range) age of 63 (56–69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13–15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received. Nephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted. This study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.

Objective To update our experience and report on features predictive of high-quality urology residents at the time of the urology match, because data predicting which medical students will mature into excellent urology residents are sparse. Methods We reviewed our experience with 84 urology residents who graduated from 2006 to 2023. Residents were independently scored 1-10 based on overall quality by the current and former Program Director. Discrepant scoring by >2 was resolved by an independent review. Associations of features from the medical student application with an excellent score (defined as 8-10) were evaluated with logistic regression. Results Discrepant scoring >2 was noted in only 5 (6%) residents. Among the 84 residents, the median overall score was 7 (range 1-10) and 36 (43%) residents had an excellent score of 8-10. Univariably, higher USMLE step II score (P = .03), election to alpha omega alpha (P = .004), no negative interview comments (P = .002), honors in OB/Gyn (P = .048) and psychiatry clerkships (P = .04), and honors in all core clinical clerkships (P < .001) were significantly associated with an excellent score. In a multivariable model, no negative interview comments (P = .003) and honors in all core clinical clerkships (P = .001) were independently associated with an excellent score (c-index 0.76). There were several notable features (sex, letters of recommendation, USMLE step I, externship at our institution, surgery clerkship grade, and rank list) that were not significantly associated with excellent residents. Conclusion We demonstrate features associated with excellent urology residents, most notably no negative interview comments and an honors grade in all core clinical clerkships. To update our experience and report on features predictive of high-quality urology residents at the time of the urology match, because data predicting which medical students will mature into excellent urology residents are sparse. We reviewed our experience with 84 urology residents who graduated from 2006 to 2023. Residents were independently scored 1-10 based on overall quality by the current and former Program Director. Discrepant scoring by >2 was resolved by an independent review. Associations of features from the medical student application with an excellent score (defined as 8-10) were evaluated with logistic regression. Discrepant scoring >2 was noted in only 5 (6%) residents. Among the 84 residents, the median overall score was 7 (range 1-10) and 36 (43%) residents had an excellent score of 8-10. Univariably, higher USMLE step II score (P = .03), election to alpha omega alpha (P = .004), no negative interview comments (P = .002), honors in OB/Gyn (P = .048) and psychiatry clerkships (P = .04), and honors in all core clinical clerkships (P < .001) were significantly associated with an excellent score. In a multivariable model, no negative interview comments (P = .003) and honors in all core clinical clerkships (P = .001) were independently associated with an excellent score (c-index 0.76). There were several notable features (sex, letters of recommendation, USMLE step I, externship at our institution, surgery clerkship grade, and rank list) that were not significantly associated with excellent residents. We demonstrate features associated with excellent urology residents, most notably no negative interview comments and an honors grade in all core clinical clerkships.