Hartwig Huland

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.This study evaluated the clinical utility of the PROGENSA PCA3 assay.This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score >or=7 versus <7, and "significant" versus "indolent" (clinical stage T1c, PSA density [PSAD] <0.15ng/ml, Gleason score in biopsy <or=6, and percent positive cores <or=33%) pCA.The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.

Prostate-specific membrane antigen (PSMA) overexpression theoretically enables targeting of prostate cancer (PCa) metastases using gallium Ga 68 (68Ga)–labeled PSMA ligands for positron emission tomography/computed tomography (PET/CT) imaging. Promising detection rates have been reported when using this approach for functional imaging of recurrent PCa; however, until now, the diagnostic accuracy of 68Ga-PSMA PET/CT for preoperatively identifying lymph node metastases (LNMs) had not been assessed. We retrospectively compared preoperative 68Ga-PSMA PET/CT lymph node (LN) findings with histologic work-up after radical prostatectomy (RP). Overall, 608 LNs containing 53 LNMs were detected during RP. LNMs were present in 12 of 30 patients (40%). The 68Ga-PSMA PET/CT scans identified 4 patients (33.3%) as LN true positive and 8 patients (66.7%) as false negative. Median size of 68Ga-PSMA-PET/CT–detected versus undetected LNMs was 13.6 versus 4.3 mm (p < 0.05). Overall sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT for LNM detection were 33.3%, 100%, 100%, and 69.2%, respectively. Per-side analyses revealed corresponding values of 27.3%, 100%, 100%, and 52.9%. Conversely, 68Ga-PSMA PET/CT enabled tumor visualization in the prostate. In 92.9% of patients, the intraprostatic tumor foci were correctly predicted. Overall, 68Ga-PSMA PET/CT is a promising tool for functional imaging; however, our initial experience revealed substantial influence of LNM size on the diagnostic accuracy of 68Ga-PSMA PET/CT. We assessed the diagnostic accuracy of 68Ga-PSMA PET/CT in high-risk prostate cancer patients prior to radical prostatectomy. We found that lymph node metastasis detection rates were substantially influenced by lymph node metastasis size.

We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer.The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases.Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes.Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies.The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms.Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good.Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with “classical” (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic “androgen-type” pathomechanism in EO-PCA.

Abstract BACKGROUND Prostate specific membrane antigen (PSMA) is a suggested target for antibody‐based therapy of prostate cancer potentially involved in the regulation of cell migration. This study was undertaken, to gain more insight on the role of PSMA in early prostate cancer and its distribution in various normal tissues. METHODS A total of 1,700 different prostate cancers treated by radical prostatectomy and 612 samples from 76 different normal tissue types were successfully analyzed by immunohistochemistry (IHC) in a tissue microarray (TMA) format. PSMA immunostaining in cancers was also compared with clinical follow‐up, preexisting HER2 expression and Ki67 labeling index data. RESULTS PSMA staining was only found in prostate epithelium and expression was higher in cancer cells than in benign tissue. PSMA staining was found in 94.1% of cancers and was significantly associated with tumor stage, high Gleason grade, preoperative PSA, and HER2 expression ( P &lt; 0.0001 each). Tumors with strong PSMA expression had a higher risk of biochemical recurrence than cancers with only weak PSMA staining intensity ( P = 0.0483). There was no significant association between PSMA expression and Ki67 labeling index ( P = 0.442). CONCLUSIONS Based on the high frequency of PSMA overexpression in all stages and grades of prostate cancer and the high prevalence of PSMA overexpression, it can be speculated that increased PSMA expression may be related with prostate cancer development rather than progression. The known function of PSMA activating cell migration would be in line with the suggested role in cancer progression and the missing association between PSMA overexpression and tumor cell proliferation. Prostate 71:281–288, 2011. © 2010 Wiley‐Liss, Inc.

Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer.To assess the clinical relevance of the fractions of Gleason patterns.Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database.To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence.Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed.Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens.Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤ 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.

Intraoperative frozen-section analysis allows real-time histologic assessment of surgical margins (SMs) and identification of candidates for nerve-sparing (NS) procedures.To examine the efficacy and oncologic safety of a systematic neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during NS radical prostatectomy (RP).From January 2002 to June 2011, 11 069 consecutive RPs were performed at the University Medical Center Hamburg-Eppendorf. Of these, 5392 (49%) were conducted with NeuroSAFE.Our NeuroSAFE approach included the whole laterorectal circumference of the prostate to determine the SM status of the complete neurovascular tissue-corresponding prostatic surface.The impact of NeuroSAFE on NS frequency, SM status, and biochemical recurrence (BCR) was analyzed by chi-square test, and by Kaplan-Meier analyses in propensity score-based matched cohorts.Positive SMs (PSMs) were detected in 1368 (25%) NeuroSAFE RPs, leading to a secondary resection of the ipsilateral neurovascular tissue. Secondary wide resection resulted in conversion to a definitive negative SM (NSM) status in 1180 (86%) patients. In NeuroSAFE RPs, frequency of NS was significantly higher (all stages: 97% vs 81%; pT2: 99% vs 92%; pT3a: 94% vs 72%; pT3b: 88% vs 40%; p<0.0001) and PSM rates were significantly lower (all stages: 15% vs 22%; pT2: 7% vs 12%; pT3a: 21% vs 32%; p<0.0001) than in the matched non-NeuroSAFE RPs. In propensity score-based comparisons, NeuroSAFE had no negative impact on BCR (pT2, p=0.06; pT3a, p=0.17, pT3b, p=0.99), and BCR-free survival of patients with conversion to NSM did not differ significantly from patients with primarily NSM (pT2, p=0.16; pT3, p=0.26). The accuracy of our NeuroSAFE approach was 97% with a false-negative rate of 2.5%. The major limitations of this study are its retrospective nature and relatively short follow-up.NeuroSAFE enables real-time histologic monitoring of the oncologic safety of a NS procedure. Systematic NeuroSAFE significantly increases NS frequencies and reduces PSMs. Patients with a NeuroSAFE-detected PSM could be converted to a prognostically more favorable NSM status by secondary wide resection.

A key prerequisite for urinary continence after radical prostatectomy (RP) is the functional length of the urethral sphincter and the stabilisation of its anatomic position within the pelvic floor.We describe our modified surgical technique for full functional-length urethra (FFLU) preservation during RP.We analysed 691 consecutive patients who underwent RP over a 12-mo period (285 without and 406 with the FFLU technique).The full functional urethra length was preserved by performing an individualised apical preparation strictly along anatomic landmarks, respecting the individual length of the intraprostatically located proportion of the urethral sphincter. Anatomic fixation of the sphincter was reached by a thorough preservation of the pelvic floor and anatomic restoration of the Mueller's ligaments.Continence rates were assessed at 7 d and 12 mo after removal of the catheter. Continence was defined as the use of no pads and no urinary leakage.The continence rates were 50.1% and 30.9% 1 wk after catheter removal (p < 0.0001) and 96.9% and 94.7% (p=0.59) at 12 mo after surgery in patients operated on with the FFLU technique versus the non-FFLU technique. In multivariate regression analysis, only the surgical technique correlated significantly with the continence status 1 wk after catheter removal. Neither the overall positive surgical margin rates nor the number of positive margins at the urethral resection border differed significantly between the FFLU and non-FFLU groups (13.6% and 0.5% vs 14.9% and 1.3%, respectively). Although the patients' baseline characteristics were similar in the two surgical groups, the patients were not preoperatively randomised, and the number of patients in the groups was asymmetric.The combination of an FFLU preparation and improved preservation of the anatomic fixation of the urethral sphincter complex resulted in significantly increased early urinary continence results.

Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

Abstract Deletions involving the chromosomal band 5q21 are among the most frequent alterations in prostate cancer. Using single-nucleotide polymorphism (SNP) arrays, we mapped a 1.3 megabase minimally deleted region including only the repulsive guidance molecule B (RGMB) and chromodomain helicase DNA-binding protein 1 (CHD1) genes. Functional analyses showed that CHD1 is an essential tumor suppressor. FISH analysis of 2,093 prostate cancers revealed a strong association between CHD1 deletion, prostate-specific antigen (PSA) biochemical failure (P = 0.0038), and absence of ERG fusion (P &amp;lt; 0.0001). We found that inactivation of CHD1 in vitro prevents formation of ERG rearrangements due to impairment of androgen receptor (AR)-dependent transcription, a prerequisite for ERG translocation. CHD1 is required for efficient recruitment of AR to responsive promoters and regulates expression of known AR-responsive tumor suppressor genes, including NKX3-1, FOXO1, and PPARγ. Our study establishes CHD1 as the 5q21 tumor suppressor gene in prostate cancer and shows a key role of this chromatin remodeling factor in prostate cancer biology. Cancer Res; 73(9); 2795–805. ©2013 AACR.

Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

PURPOSE Both the performance characteristics of prostate-specific membrane antigen positron emission tomography and insurance approval improves with increasing prostate-specific antigen (PSA) level causing some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) after PSA failure. Yet, it is unknown for men with at most one high-risk factor (ie, pT3/4 or prostatectomy [p] Gleason score 8-10) whether a PSA level exists above which initiating sRT is associated with increased all-cause mortality (ACM)-risk and was investigated. METHODS Using a multinational database of 25,551 patients with pT2-4N0 or NXM0 prostate cancer, multivariable Cox regression analysis evaluated whether an association with a significant increase in ACM-risk existed when sRT was delivered above a prespecified PSA level beginning at 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of radical prostatectomy, established prostate cancer prognostic factors, institution, and the time-dependent use of androgen deprivation therapy. RESULTS After a median follow-up of 6.00 years, patients who received sRT at a PSA level &gt;0.25 ng/mL had a significantly higher ACM-risk (AHR, 1.49; 95% CI, 1.11 to 2.00; P = .008) compared with men who received sRT when the PSA was ≤0.25 mg/mL. This elevated ACM-risk remained significant for all PSA cutpoints up to 0.50 ng/mL but was not significant at PSA cutpoint values below 0.25 ng/mL. CONCLUSION Among patients with at most one high-risk factor, initiating sRT above a PSA level of 0.25 ng/mL was associated with increased ACM-risk.

When a second transurethral resection was routinely performed 8 to 14 days after the initial transurethral resection in 46 patients for stage T1 bladder tumors residual disease was found in 20 despite the surgical report of complete resection in 40. In only 13 patients was residual tumor noted at repeat resection by the senior urologist performing the operation and residual tumor was confirmed histologically in 10 of them. The extent of the lesion is easily misjudged even by experienced surgeons. Early cystoscopy cannot exclude residual tumor. Residual tumor is an important cause of early recurrence and repeat resection of stage T1 lesions is recommended.

Conventional gray scale ultrasound has a low sensitivity and specificity for prostate cancer detection. Better imaging modalities are needed. To determine sensitivity and specificity for prostate cancer detection with ultrasound-based real-time elastography (elastography) in patients scheduled for radical prostatectomy (RP). Between July and October 2007, 109 patients with biopsy-proven localized prostate cancer (PCa) underwent elastography before RP. The investigator was blinded to clinical data. A EUB-6500HV ultrasound system with a V53W 7.5 MHz end-fire transrectal probe was used preoperatively. Areas found to be suspicious for PCa were recorded for left and right side of the apex, mid-gland, and base. These findings were correlated with the obtained whole-mount sections after RP. Sensitivity and specificity for detecting PCa were 75.4% and 76.6%, respectively. A total of 439 suspicious areas in elastography were recorded, and 451 cancerous areas were found in the RP specimens. Positive predictive value, negative predictive value, and accuracy for elastography were 87.8%, 59%, and 76%, respectively. Nevertheless, there are limitations to our studies because we investigated specific patients scheduled for RP with apparent PCa. Whether elastography is practical as a diagnostic tool or can be used to target a biopsy and be at least as sensitive in tumor detection as extended biopsy schemes has yet to be determined. Elastography can detect prostate cancer foci within the prostate with good accuracy and has potential to increase ultrasound-based PCa detection. Further studies need to be done to approve these data and to evaluate whether tumor detection can be increased by elastography-guided biopsies.

There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments.We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients.The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals.Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.

We explored the yield of saturation biopsy and developed a nomogram predicting the probability of prostate cancer (PCa) on the basis of saturation biopsy. Between 2001 and 2004, saturation biopsies (average of 24 cores) were performed in 161 men with persistently elevated prostate specific antigen (PSA) level (median, 9 ng/ml). All had at least two previously negative, eight-core biopsy sessions. PCa predictors on saturation biopsy were integrated within multivariate nomograms. PCa detection was 41% (n = 66 of 161). PSA density and transition zone volume were the most significant predictors of PCa on saturation biopsy. The accuracy of the nomogram with the best performance characteristics was 72%. Saturation biopsy may be indicated in men with a persistent suspicion of PCa. High-risk individuals can be identified accurately with our nomogram.

No AccessJournal of UrologyClinical Urology: Original Article1 Jan 1997Urodynamic Evaluation of Changes in Urinary Control After Radical Retropubic Prostatectomy P. Hammerer and H. Huland P. HammererP. Hammerer More articles by this author and H. HulandH. Huland More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)65334-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Urodynamic evaluations were done in patients before and after radical prostatectomy to obtain more information about the factors that affect continence. Materials and Methods: Urodynamic testing was done in 82 patients before, and 6 to 8 weeks and 6 months (9 cases) after radical prostatectomy. Evaluation included measurement of cystometric bladder capacity, compliance, functional profile length, maximal urethral closure pressure, maximal urethral closure pressure during voluntary contraction of the external sphincter, residual urine, maximal flow rate and bladder instability. Results: The continence rate was 33.4, 69.4, 84.7 and 90.9% at 1, 3, 6 and 12 months after radical prostatectomy, respectively. Mean functional urethral length decreased from 61 mm. preoperatively to 25.9 mm. postoperatively, maximal urethral pressure from 89.6 to 65.2 cm. water and bladder capacity from 338.7 to 278.8 ml. Bladder instability was found in 17 and 41% of cases before and directly after radical prostatectomy, respectively. There was a statistically significant difference in maximal urethral closure pressure (68.1 versus 53.1 cm. water) as well as functional urethral length (27.6 versus 20.5 mm.) in continent versus incontinent patients, respectively. Urodynamic examination 6 months after prostatectomy showed an increase in functional profile length and maximal urethral pressure, while bladder measurements did not change significantly. Conclusions: After radical prostatectomy significant changes in bladder and sphincter measurements are noted. Urethral closure pressure, functional urethral length and bladder stability are significantly urodynamic factors that influence continence after radical prostatectomy. References 1 : Perioperative and postoperative complications from bilateral pelvic lymphadenectomy and radical retropubic prostatectomy.. J. Urol.1987; 137: 1189. Abstract, Google Scholar 2 : Radical retropubic prostatectomy: improved anastomosis and urinary continence.. Urol. Clin. N. Amer.1990; 17: 679. Google Scholar 3 : Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy.. J. Urol.1993; 150: 905. 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Abstract, Google Scholar Department of Urology, University of Hamburg, Hamburg, Germany.© 1997 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byBianco F, Albala D, Belkoff L, Miles B, Peabody J, He W, Bradt J, Haas G and Ahlering T (2014) A Randomized, Double-Blind, Solifenacin Succinate versus Placebo Control, Phase 4, Multicenter Study Evaluating Urinary Continence after Robotic Assisted Radical ProstatectomyJournal of Urology, VOL. 193, NO. 4, (1305-1310), Online publication date: 1-Apr-2015.Abraham N, Makarov D, Laze J, Stefanovics E, Desai R and Lepor H (2010) Patient Centered Outcomes in Prostate Cancer Treatment: Predictors of Satisfaction Up to 2 Years After Open Radical Retropubic ProstatectomyJournal of Urology, VOL. 184, NO. 5, (1977-1981), Online publication date: 1-Nov-2010.Teber D, Sofikerim M, Ates M, Gözen A, Güven O, Sanli Ö and Rassweiler J (2010) Is Type 2 Diabetes Mellitus a Predictive Factor for Incontinence After Laparoscopic Radical Prostatectomy? A Matched Pair and Multivariate AnalysisJournal of Urology, VOL. 183, NO. 3, (1087-1091), Online publication date: 1-Mar-2010.Loughlin K and Prasad M (2010) Post-Prostatectomy Urinary Incontinence: A Confluence of 3 FactorsJournal of Urology, VOL. 183, NO. 3, (871-877), Online publication date: 1-Mar-2010.Song C, Doo C, Hong J, Choo M, Kim C and Ahn H (2007) Relationship Between the Integrity of the Pelvic Floor Muscles and Early Recovery of Continence After Radical ProstatectomyJournal of Urology, VOL. 178, NO. 1, (208-211), Online publication date: 1-Jul-2007.Rocco F, Carmignani L, Acquati P, Gadda F, Dell’Orto P, Rocco B, Bozzini G, Gazzano G and Morabito A (2018) Restoration of Posterior Aspect of Rhabdosphincter Shortens Continence Time After Radical Retropubic ProstatectomyJournal of Urology, VOL. 175, NO. 6, (2201-2206), Online publication date: 1-Jun-2006.GIANNANTONI A, MEARINI E, Di STASI S, MEARINI L, BINI V, PIZZIRUSSO G and PORENA M (2018) ASSESSMENT OF BLADDER AND URETHRAL SPHINCTER FUNCTION BEFORE AND AFTER RADICAL RETROPUBIC PROSTATECTOMYJournal of Urology, VOL. 171, NO. 4, (1563-1566), Online publication date: 1-Apr-2004.WILLE S, SOBOTTKA A, HEIDENREICH A and HOFMANN R (2018) Pelvic Floor Exercises, Electrical Stimulation and Biofeedback After Radical Prostatectomy: Results of a Prospective Randomized TrialJournal of Urology, VOL. 170, NO. 2, (490-493), Online publication date: 1-Aug-2003.HAUTMANN R (2018) Urinary Diversion: Ileal Conduit to NeobladderJournal of Urology, VOL. 169, NO. 3, (834-842), Online publication date: 1-Mar-2003.Coakley F, Eberhardt S, Kattan M, Wei D, Scardino P and Hricak H (2018) Urinary Continence After Radical Retropubic Prostatectomy: Relationship with Membranous Urethral Length on Preoperative Endorectal Magnetic Resonance ImagingJournal of Urology, VOL. 168, NO. 3, (1032-1035), Online publication date: 1-Sep-2002.SHAH O, MELAMED J and LEPOR H (2018) ANALYSIS OF APICAL SOFT TISSUE MARGINS DURING RADICAL RETROPUBIC PROSTATECTOMYJournal of Urology, VOL. 165, NO. 6 Part 1, (1943-1949), Online publication date: 1-Jun-2001.JOHN H, HAURI D, LEUENER M, REINECKE M and MAAKE C (2018) EVIDENCE OF TRIGONAL DENERVATION AND REINNERVATION AFTER RADICAL RETROPUBIC PROSTATECTOMYJournal of Urology, VOL. 165, NO. 1, (111-113), Online publication date: 1-Jan-2001.TWISS C, MARTIN S, SHORE R and LEPOR H (2018) A CONTINENCE INDEX PREDICTS THE EARLY RETURN OF URINARY CONTINENCE AFTER RADICAL RETROPUBIC PROSTATECTOMYJournal of Urology, VOL. 164, NO. 4, (1241-1247), Online publication date: 1-Oct-2000.GROUTZ A, BLAIVAS J, CHAIKIN D, WEISS J and VERHAAREN M (2018) THE PATHOPHYSIOLOGY OF POST-RADICAL PROSTATECTOMY INCONTINENCE: A CLINICAL AND VIDEO URODYNAMIC STUDYJournal of Urology, VOL. 163, NO. 6, (1767-1770), Online publication date: 1-Jun-2000.JOHN H, SULLIVAN M, BANGERTER U, HAURI D and YALLA S (2018) EFFECT OF RADICAL PROSTATECTOMY ON SENSORY THRESHOLD AND PRESSURE TRANSMISSIONJournal of Urology, VOL. 163, NO. 6, (1761-1766), Online publication date: 1-Jun-2000. Volume 157Issue 1January 1997Page: 233-236 Advertisement Copyright & Permissions© 1997 by American Urological Association, Inc.MetricsAuthor Information P. Hammerer More articles by this author H. Huland More articles by this author Expand All Advertisement PDF downloadLoading ...

Previous reports indicate that as many as 43% of men with low grade PCa at biopsy will be diagnosed with high-grade PCa at RP. We explored the rate of upgrading from biopsy to RP specimen in our contemporary cohort, and developed a model capable of predicting the probability of biopsy Gleason sum upgrading. The study cohort consisted of 2982 men treated with RP, with available clinical stage, serum prostate specific antigen and biopsy Gleason scores. These clinical data were used as predictors in multivariate logistic regression models (LRM) addressing the rate of Gleason sum upgrading between biopsy and RP pathology. LRM regression coefficients were used to develop a nomogram predicting the probability of Gleason sum upgrading and was subjected to 200 bootstrap resamples for internal validation and to reduce overfit bias. Overall, 875 patients were upgraded (29.3%). In multivariate LRMs, all predictors were highly significant (all p values <0.0001). Bootstrap-corrected predictive accuracy of the nomogram predicting the probability of Gleason sum upgrading between biopsy and RP was 0.804. We developed a highly accurate clinical aid for treatment decision-making. It may prove useful when the possibility of a more aggressive Gleason variant may change the treatment options.

We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents.Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots.The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram.The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Despite the high number of previous studies, the role of p53 alterations in prostate cancer is not clearly defined. To address the role of p53 alterations in prostate cancer biology, a total of 2514 cancers treated by radical prostatectomy were successfully analyzed by immunohistochemistry in a tissue microarray format. Overall a low rate of p53-positive tumors was found (2.5%). A significant underestimation of p53-positive cases was excluded by subsequent large section analyses and direct sequencing of the p53 gene in subsets of our patients. Large section analysis of 23 cases considered negative on the tissue microarray yielded only one weakly p53-positive tumor. Only 4 out of 64 (6.4%) high-grade tumors, that were considered negative for p53 by immunohistochemistry, presented exon 5–8 mutations. These data suggest a high sensitivity of our immunohistochemistry approach and confirm the overall low frequency of p53 alterations in clinically localized prostate cancer. A positive p53 immunostaining was strongly associated with presence of exon 5–8 mutations (P<0.0001), advanced pT-stage (P<0.0001), high Gleason grade (P<0.0001), positive surgical margins (P=0.03) and early biochemical tumor recurrence (P<0.0001). A higher rate of positive p53 immunostaining was detected in late-stage diseases including metastatic prostate cancer (P=0.0152) and hormone-refractory tumors (P=0.0003). Moreover, p53 expression was identified as an independent predictor of biochemical tumor recurrence in the subgroup of low- and intermediate-grade cancers. In summary, the results of this study show that p53 mutations characterize a small biologically aggressive subgroup of prostate cancers with a high risk of progression after prostatectomy. The rate of p53 alterations increases with prostate cancer progression.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration toward organ-confined cancers allows performance of a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter-preserving ligation of the distal part of the Santorini plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique, which is demonstrated in the attached DVD. Furthermore, indication, oncologic outcome, and functional results addressing postoperative urinary continence and potency are discussed.

Urinary prostate cancer gene 3 (PCA3) represents a promising novel marker of prostate cancer detection. To test whether urinary PCA3 assay improves prostate cancer (PCa) risk assessment and to construct a decision-making aid in a multi-institutional cohort with pre–prostate biopsy data. PCA3 assay cut-off threshold analyses were followed by logistic regression models which used established predictors to assess PCa-risk at biopsy in a large multi-institutional data set of 809 men at risk of harboring PCa. Regression coefficients were used to construct four sets of nomograms. Predictive accuracy (PA) estimates of biopsy outcome predictions were quantified using the area under the curve of the receiver operator characteristic analysis in models with and without PCA3. Bootstrap resamples were used for internal validation and to reduce overfit bias. The extent of overestimation or underestimation of the observed PCa rate at biopsy was explored graphically using nonparametric loss-calibration plots. Differences in PA were tested using the Mantel-Haenszel test. Finally, nomogram-derived probability cut-offs were tested to assess the ability to identify patients with or without PCa. PCA3 was identified as a statistically independent risk factor of PCa at biopsy. Addition of a PCA3 assay improved bootstrap-corrected multivariate PA of the base model between 2% and 5%. The highest increment in PA resulted from a PCA3 assay cut-off threshold of 17, where a 5% gain in PA (from 0.68 to 0.73, p = 0.04) was recorded. Nomogram probability–derived risk cut-off analyses further corroborate the superiority of the PCA3 nomogram over the base model. PCA3 fulfills the criteria for a novel marker capable of increasing PA of multivariate biopsy models. This novel PCA3-based nomogram better identifies men at risk of harboring PCa and assists in deciding whether further evaluation is necessary.

Objectives: To up date counselling of patients in an experienced center, we assessed intraoperative and perioperative complications in a consecutive series of contemporary radical retropubic prostatectomy for localized prostate cancer. Methods: In a prospective study, we analyzed all intraoperative and perioperative complications within 30 days in a consecutive series of 1243 patients undergoing radical prostatectomy between January 1999 and February 2002. All adverse events were graduated in major and minor complications by their severity and sequel. Results: There were no deaths. Overall, 996 patients (80.2%) were not affected by any complication. Major complications were observed in 50 patients (4.0%), minor complications in 197 (15.8%). Pelvic lymphadenectomy was performed in 861 (69.3%) patients. This procedure was associated with a significantly higher rate of lymphoceles requiring a drainage, 4.2% versus 0.3% (p<0.006) and a higher rate of deep venous thrombosis, 1.4% versus 0.5% (p<0.2), respectively. Conclusion: Radical retropubic prostatectomy is a safe surgical procedure. Postoperatively the majority of our patients was not compromised by any complication within 30 days. Furthermore, due to a higher rate of lymphoceles and thromboembolic events the indication for pelvic lymphadenectomy should be considered carefully.

The aim of this study is to identify anxiety, depression and post-traumatic stress disorder in prostate cancer patients and to investigate the association with social support and health-related quality of life. A total of 511 men who had undergone prostatectomy were surveyed during ambulatory follow-up care for an average of 27 months after surgery using standardised self-report measures (e.g. Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist--Civilian Version, Illness-Specific Social Support Scale, Short-Form Health Survey). Seventy-six per cent of patients evaluated their disease as 'not' or a 'little threatening'. The cancer diagnosis and uncertainty were most frequently reported as 'distressing', while medical treatment and doctor-patient interaction were most frequently evaluated as 'most helpful'. The number of patients reporting increased levels of psychological distress was 16%, with 6% demonstrating signs of having severe mental health problems'. No higher levels of anxiety and depression were observed in cancer patients compared with age-adjusted normative comparison groups. Lack of positive support, detrimental interactions and perceived threat of cancer were found to be predictors of psychological co-morbidity (P < 0.001). Lack of positive support, detrimental interactions, threat of cancer, disease stage and age significantly predicted mental health (P < 0.001), whereas the impact of social support on physical health was rather weak. Findings emphasise the need for routine psychosocial screening.

No AccessJournal of UrologyAdult Urology: Oncology: Prostate/Testis/Penis/Urethra1 Jun 2005DEVELOPMENT AND VALIDATION OF A NOMOGRAM PREDICTING THE OUTCOME OF PROSTATE BIOPSY BASED ON PATIENT AGE, DIGITAL RECTAL EXAMINATION AND SERUM PROSTATE SPECIFIC ANTIGEN PIERRE I. KARAKIEWICZ, SERGE BENAYOUN, MICHAEL W. KATTAN, PAUL PERROTTE, LUC VALIQUETTE, PETER T. SCARDINO, ILIAS CAGIANNOS, HANS HEINZER, SIMON TANGUAY, ARMEN G. APRIKIAN, HARTWIG HULAND, and MARKUS GRAEFEN PIERRE I. KARAKIEWICZPIERRE I. KARAKIEWICZ Supported by the Fonds de la Recherche en Santé du Québec and by the Canadian Urological Association Scholarship Fund. More articles by this author , SERGE BENAYOUNSERGE BENAYOUN More articles by this author , MICHAEL W. KATTANMICHAEL W. KATTAN More articles by this author , PAUL PERROTTEPAUL PERROTTE More articles by this author , LUC VALIQUETTELUC VALIQUETTE More articles by this author , PETER T. SCARDINOPETER T. SCARDINO Supported by the Fonds de la Recherche en Santé du Québec and by the Canadian Urological Association Scholarship Fund. More articles by this author , ILIAS CAGIANNOSILIAS CAGIANNOS More articles by this author , HANS HEINZERHANS HEINZER More articles by this author , SIMON TANGUAYSIMON TANGUAY More articles by this author , ARMEN G. APRIKIANARMEN G. APRIKIAN More articles by this author , HARTWIG HULANDHARTWIG HULAND More articles by this author , and MARKUS GRAEFENMARKUS GRAEFEN More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000158039.94467.5dAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. Materials and Methods: We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. Results: PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. Conclusions: A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa. References 1 : Predictive modeling for the presence of prostate carcinoma using clinical, laboratory, and ultrasound parameters in patients with prostate specific antigen levels ≤ 10 ng/mL. Cancer2003; 98: 1417. Google Scholar 2 : Novel artificial neural network for early detection of prostate cancer. J Clin Oncol2002; 20: 921. Google Scholar 3 : A nomogram for predicting a positive repeat prostate biopsy in patients with a previous negative biopsy session. J Urol2003; 170: 1184. Link, Google Scholar 4 : Prospective evaluation of prostate-specific antigen density and systematic biopsies for early detection of prostatic carcinoma. Urology1994; 43: 44. Google Scholar 5 : Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer. J Clin Oncol1999; 17: 168. Google Scholar 6 : Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer. J Clin Oncol2000; 18: 3352. Google Scholar 7 : Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer. Urology2001; 58: 393. Google Scholar 8 : A validation of two preoperative nomograms predicting recurrence following radical prostatectomy in a cohort of European men. Urol Oncol2002; 7: 141. Google Scholar 9 : International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy. J Clin Oncol2002; 20: 3206. Google Scholar 10 : Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol1999; 17: 1499. Google Scholar 11 : Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer. J Clin Oncol2002; 20: 951. Google Scholar 12 : Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer. J Urol2004; 171: 200. Link, Google Scholar 13 : Development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/mL. Urology1999; 54: 709. Google Scholar 14 : Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection. Urology2002; 59: 261. Google Scholar 15 : A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst1998; 90: 766. Google Scholar 16 : The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: is biopsy always required?. J Urol2002; 168: 1990. Link, Google Scholar 17 : An algorithm combining age, total prostate-specific antigen (PSA), and percent free PSA to predict prostate cancer: results on 4298 cases. Urology1998; 52: 455. Google Scholar 18 : Age, prostate specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer. Urology2001; 57: 1100. Google Scholar 19 : Who predicts better: a clinician or a nomogram?. J Urol2003; 169: 293. abstract 1140. Google Scholar 20 : Comparisons of nomograms and urologists' predictions in prostate cancer. Semin Urol Oncol2002; 20: 82. Google Scholar Department of Urology, University of Montreal (PIK, SB, PP, LV), Division of Urology, McGill University (ST, AGA), Montreal, Quebec, Department of Urology, University of Ottawa (IC), Ontario, Canada, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York (MWK, PTS), and Department of Urology, University of Hamburg, Hamburg, Germany (HH, MG)© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byPoyet C, Wettstein M, Lundon D, Bhindi B, Kulkarni G, Saba K, Sulser T, Vickers A and Hermanns T (2018) External Evaluation of a Novel Prostate Cancer Risk Calculator (ProstateCheck) Based on Data from the Swiss Arm of the ERSPCJournal of Urology, VOL. 196, NO. 5, (1402-1407), Online publication date: 1-Nov-2016.Sun L, Caire A, Robertson C, George D, Polascik T, Maloney K, Walther P, Stackhouse D, Lack B, Albala D and Moul J (2018) Men Older Than 70 Years Have Higher Risk Prostate Cancer and Poorer Survival in the Early and Late Prostate Specific Antigen ErasJournal of Urology, VOL. 182, NO. 5, (2242-2249), Online publication date: 1-Nov-2009.Eyre S, Ankerst D, Wei J, Nair P, Regan M, Bueti G, Tang J, Rubin M, Kearney M, Thompson I and Sanda M (2018) Validation in a Multiple Urology Practice Cohort of the Prostate Cancer Prevention Trial Calculator for Predicting Prostate Cancer DetectionJournal of Urology, VOL. 182, NO. 6, (2653-2658), Online publication date: 1-Dec-2009.Benecchi L, Pieri A, Melissari M, Potenzoni M and Pastizzaro C (2018) A Novel Nomogram to Predict the Probability of Prostate Cancer on Repeat BiopsyJournal of Urology, VOL. 180, NO. 1, (146-149), Online publication date: 1-Jul-2008. Volume 173Issue 6June 2005Page: 1930-1934 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordsprostatic neoplasmsnomogramsbiopsyvalidation studiesMetricsAuthor Information PIERRE I. KARAKIEWICZ Supported by the Fonds de la Recherche en Santé du Québec and by the Canadian Urological Association Scholarship Fund. More articles by this author SERGE BENAYOUN More articles by this author MICHAEL W. KATTAN More articles by this author PAUL PERROTTE More articles by this author LUC VALIQUETTE More articles by this author PETER T. SCARDINO Supported by the Fonds de la Recherche en Santé du Québec and by the Canadian Urological Association Scholarship Fund. More articles by this author ILIAS CAGIANNOS More articles by this author HANS HEINZER More articles by this author SIMON TANGUAY More articles by this author ARMEN G. APRIKIAN More articles by this author HARTWIG HULAND More articles by this author MARKUS GRAEFEN More articles by this author Expand All Advertisement PDF downloadLoading ...

We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort.Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots.Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%.We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

We have previously have reported a tree structured regression model for predicting SS-ECE. Others recently reported a logistic regression based SS-ECE nomogram. We developed a nomogram and compared the performance and discriminant properties of the tree regression and the nomogram in a contemporary cohort of European patients treated with radical retropubic prostatectomy.The cohort consisted of 1,118 patients with pretreatment prostate specific antigen 0.1 to 73.2 ng/ml (median 6.6). Each of the 2,236 prostate lobes was considered separately. Clinical stage, pretreatment PSA, biopsy Gleason sum, percent positive cores and percent cancer in the biopsy specimen were used as predictors in a logistic regression model predicting SS-ECE. Regression coefficients were then used to generate an SS-ECE nomogram. Performance characteristics and discriminant properties of the previously published tree regression were also tested in the same cohort. For internal validation and to decrease overfit bias 200 bootstrap re-samples were applied to accuracy estimates for each method.ECE was present in 303 of 1,118 radical retropubic prostatectomy specimens (27%) and in 385 lobes (17%). In logistic regression models all variables were statistically significant multivariate predictors of SS-ECE except the percent of positive biopsy cores (p = 0.7). Bootstrap corrected predictive accuracy of the SS-ECE nomogram was 0.840 vs 0.700 for the tree regression model.Logistic regression based nomogram predictions of SS-ECE are highly accurate and represent a valuable aid for assessing the risk of ECE prior to surgery.

Recent literature describes indications for a more-complex course of fibres of the neurovascular bundle (NVB), despite the widely held assumption that it is gathered at the rectolateral side of the prostate. The objective of this study therefore was to determine the typical pattern of nerve distribution along the prostatic capsule.Permanent sections of 31 patients, who underwent non-nerve-sparing radical prostectomy (RP) at our institution, were investigated. A total of 186 slides taken from the apex, mid-part, and base of the prostate was analyzed by microscopy. Before microscopy, slides were divided into 12 sectors and numbered clockwise starting from "1" for left ventral sides to "6" for the rectal sides (accordingly, "12"-"7" for right half). Every single nerve and ganglion in the prostatic capsule and the periprostatic tissue was counted in each sector.The majority of nerves found in the sectors corresponded to the typical location of the NVB at the rectolateral sides of the prostate (4/5 or 8/9 o'clock sectors). In these two sectors, a median of 45.9-65.6% of counted nerves per half was found. However, a significant amount of nerves (21.5%-28.5%) was detected above the horizontal line.We conclude that 1/5-1/4 of nerves can be found along the ventral circumference of the prostatic capsule. To preserve a maximum number of nerves, we therefore recommend a modification of the surgical technique by focusing on a high incision for nerve sparing on the ventral parts of the prostate.

OBJECTIVE To assess the contemporary inter‐institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi‐institutional cohort from four continents, as cystoscopy and urinary cytology represent the ‘gold standards’ for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies. PATIENTS AND METHODS Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age‐ and gender‐adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re‐samples. RESULTS The mean (range across institutions) age of the patients was 65 (48–69) years and 75 (67–87)% were men. Cytology was positive in 19 (10–38)% of patients; recurrence was identified in 35 (27–54)% of patients. The sensitivity was 38–65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution‐specific predictive accuracy adjusted for gender and age was 0.627–0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres. CONCLUSIONS The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).

The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level.Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations.Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed.Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.

To examine the stage migration patterns in patients treated with radical prostatectomy (RP) for prostate cancer in Europe and in the USA in the last 20 years.Between 1988 and 2005, RP was performed in 11 350 men: 5739 from Europe and 5611 from the USA. Independent-samples t-test and the chi-square test were, respectively, used for comparisons of means and proportions. The trend test was used to test the statistical significance of trends in proportions over time. RESULTS; Temporal patterns in patients' age, stage and PSA level at presentation were similar on both continents. Conversely, temporal patterns in Gleason sum distribution differed. In the USA, the rate of biopsy Gleason sums of 2-5 decreased from 32.8% to 0.2% (P < 0.001), while the rate of Gleason sums of 7 and 8-10 increased (P < 0.001). Conversely, in Europe the rate of Gleason sums of 6 increased from 40% to 64% (P < 0.001) at the expense of all other Gleason sums. At RP, the rate of Gleason sums of 2-5 decreased on both continents and the rate of a Gleason sum of 7 increased in the USA. Moreover, no important differences in pathological stage trends (organ confinement, extracapsular extension and seminal vesicle invasion) distinguished either population. Finally, the rate of lymph node involvement increased in the USA but remained stable in Europe.Stage and grade migration affected the USA and Europe to different extents. These differences should be accounted for when prediction tools or comparisons between the USA and Europe are considered.

Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial.Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen.Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available.All patients were treated with RP.PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3.PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size.PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.

Open nerve-sparing retropubic prostatectomy (nsRP) is still the most common surgical approach for the treatment of localised prostate cancer. Even though the principles of the technique and its oncological efficacy have often been published, ongoing refinements allow further improvements in functional outcome and morbidity.To describe our current technique of open nsRP with data addressing urinary continence, potency, cancer control rates, and perioperative morbidity.Our analyses relied on 1150 patients who were treated with nsRP in the Martini-Clinic by two high-volume surgeons from April 2005 to December 2007.Key elements are a selective ligation of the dorsal vein complex and early release of the neurovascular bundles using a high anterior tension- and energy-free intrafascial technique. During dissection of the urethra, its posterior insertion at Denonvilliers' fascia (DF) is preserved. DF is left in situ, and it is selectively opened above the seminal vesicles (SV). The SV are completely removed inside DF, and five muscle-sparing interrupted sutures are used for anastomosis.Functional and oncological outcome data were prospectively assessed using validated questionnaires. Moreover, intra- and perioperative morbidity were evaluated.Age and extent of nerve-sparing approach influenced urinary continence and potency. Complete urinary continence 1 yr after nsRP was found in 97.4% (men <60 yr) to 84.1% (men >70 yr) of patients. In preoperative potent men, erections sufficient for intercourse were reported between 84-92% and 58.3-70% of patients following bilateral and unilateral nerve sparing, respectively. Median blood loss was 580 ml (range: 130-1800 ml), and the transfusion rate was 4.3%. Median operative time was 165 min (range: 85-210 min). In organ-confined cancers, recurrence-free survival and cancer-specific-survival 10 yr after retropubic prostatectomy were 87% and 98.3%, respectively.Open intrafascial nsRP combines excellent long-term cancer control rates with superior functional outcome and a low morbidity.

We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele.To determine the presence of XMRV in non-familial prostate cancer samples.RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR.XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele.XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11-17%).

Abstract Background: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival. Methods: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch™; Veridex) approved for clinical use. Results: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (≥80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%–85%) and correlated (Kendall τ, 0.60–0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status. Conclusions: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.

Number of intratumoral mast cells predicts survival in various cancers. The prognostic significance of such mast cells in surgically treated prostate cancer is unknown.Mast cell densities were determined in prostate cancer samples of more than 2,300 hormone-naïve patients using a tissue microarray format in correlation with clinical follow-up data. Mast cells were visualized immunohistochemically (c-kit). All patients were homogeneously treated by radical prostatectomy at a single institution.Mast cells were present in 95.9% of the tumor samples. Median mast cell number on the tissue spot was 9 (range: 0-90; median density: 31 mast cells/mm(2)). High mast cell densities were significantly associated with more favorable tumors having lower preoperative prostate-specific antigen (P = 0.0021), Gleason score (P < 0.0001) and tumor stage (P < 0.0001) than tumors with low mast cell densities. Prostate-specific antigen recurrence-free survival significantly (P = 0.0001) decreased with decline of mast cell density showing poorest outcome for patients without intratumoral mast cells. In multivariate analysis mast cell density narrowly missed to add independent prognostic information (P = 0.0815) for prostate-specific antigen recurrence.High intratumoral mast cell density is associated with favorable tumor characteristics and good prognosis in prostate cancer. This finding is consistent with a role of mast cells in the immunological host-defense reaction on prostate cancer. Triggering mast cell activity might expand immunotherapeutic strategies in prostate cancer.

Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown.To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization.Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT(2) cancers, 38.5%/9.8% of 379 pT(3a) cancers, 43.5%/8.9% of 237 pT(3b) cancers, 40.7%/14.8% of 27 pT(4) cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence.8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application.

• To investigate the pathological characteristics and the rates of biochemical recurrence (BCR) -free survival after radical prostatectomy (RP) in men with high-risk prostate cancer.• Of 4760 patients treated with RP for prostate cancer at three institutions, 293 patients (6.2%) had clinical stage T3, 269 (5.7%) had a biopsy Gleason sum ≥ 8, 370 (7.8%) had preoperative PSA ≥ 20 ng/mL and 887 (18.6%) were considered high-risk according to the D'Amico classification (clinical stage ≥ T2c or prostate-specific antigen (PSA) ≥ 20 ng/mL or biopsy Gleason sum ≥ 8). • Actuarial BCR-free survival probabilities after RP and the rate of favourable pathology (organ-confined cancer, negative surgical margin and Gleason ≤ 7) were assessed.• Median follow up was 2.4 years and 1179 (24.8%) patients had follow up beyond 5 years. • The rate of favourable pathology increased in the following order: clinical stage T3 (13.7%), biopsy Gleason ≥ 8 (16.4%), the D'Amico high-risk group (21.4%) and PSA ≥ 20 ng/mL (21.6%). • The 5-year BCR-free survival probabilities were 35.4% for Gleason ≥ 8, 39.8% for PSA ≥ 20 ng/mL, 47.4% for D'Amico high-risk group and 51.6% for clinical stage T3. • Patients with only one risk factor had the most favourable 5-year BCR-free survival (50.3%), relative to patients with two or more risk factors (27.5%)• Men with clinically localized high-risk prostate cancer do not have a uniformly poor prognosis after RP. • The rate of favourable pathology and of BCR-free survival may vary substantially, depending on the definition used. • RP should be considered a valid treatment modality for high-risk prostate cancer patients, as many can be surgically down-staged.

Abstract Purpose: The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer. Experimental Design: A tissue microarray containing &amp;gt;2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization. Results: Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P &amp;lt; 0.0001, both), advanced pT stage (P &amp;lt; 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P &amp;lt; 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%). Conclusions: Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches. Clin Cancer Res; 16(5); 1553–60

The effect of preservation of neurovascular bundles (NVBs) during radical prostatectomy (RP) on continence remains controversial.To analyze if the differing surgical techniques of nerve-sparing (NS) versus non-nerve-sparing (NNS) RP and not the preservation of the NVB itself may be responsible for differences in continence rates.A total of 18 427 men who underwent RP from 2002 to 2014 in a single high-volume center were analyzed retrospectively. Patients with bilateral NS RP, with primary NNS RP, and with bilateral secondary resection of the NVBs for positive frozen-section results after an initial bilateral nerve sparing (secNNS) RP were studied.NS, NNS, or secNNS RP.Multivariable and propensity score matched analyses adjusting for age, prostate volume, and year of surgery were performed to assess differences in continence rates after RP. Continence was defined as the use of no or one safety pad per day.Post-RP urinary continence rates at 1 wk, 3 mo, and 12 mo were 59.8%, 76.2%, 85.4% in the NS group, 39.5%, 59.5%, and 87.0% in the secNNS group, and 29.1%, 52.8%, and 70.5% in the NNS group. Continence rates at 12 mo after surgery did not differ significantly between patients who had bilateral NS and patients who had resection of both NVBs after an initial nerve-sparing technique (secNNS). In contrast, when comparing the NNS study groups with initial NNS versus secNNS, the latter group had significantly higher continence rates after 12 mo.Our results indicate that the meticulous apical dissection associated with the NS RP technique rather than the preservation of the NVBs itself may have a positive impact on long-term urinary continence rates.We looked at continence rates after nerve-sparing (NS) versus non-NS radical prostatectomy (RP). NS surgery technique but not the preservation of the neurovascular bundles led to improved long-term continence rates after RP.

The Epstein criteria represent the most widely used scheme for prediction of clinically insignificant prostate cancer (PCa). However, they were never validated in European men. We assessed the rate of unfavorable prostate cancer (Gleason 7-10 or non-organ-confined disease) in a cohort of 366 men who fulfilled the Epstein clinically insignificant PCa criteria.Between 1996 and 2006, 2580 men underwent radical prostatectomy at a single academic European institution. Of those, 366 fulfilled the contemporary Epstein clinically insignificant PCa criteria. Analyses targeted the rate of pathologically unfavorable prostate cancer, defined as either Gleason sum 7-10 or non-organ-confined disease, or a combination of these characteristics in patients with clinically insignificant PCa.Gleason 7-10 prostate cancer at radical prostatectomy was found in 88 patients (24%) with clinically insignificant PCa. In addition, 30 (34.1%) of the 88 patients harboured non-organ-confined disease. Consequently, the contemporary Epstein criteria for clinically insignificant PCa were inaccurate in 24% of patients.The Epstein clinical insignificant PCa criteria may underestimate the true nature of prostate cancer in as many as 24% of European patients. Therefore, caution is advised when treatment decisions are based solely on these criteria.

Deletion of 3p13 has been reported from about 20% of prostate cancers. The clinical significance of this alteration and the tumour suppressor gene(s) driving the deletion remain to be identified. We have mapped the 3p13 deletion locus using SNP array analysis and performed fluorescence in situ hybridization (FISH) analysis to search for associations between 3p13 deletion, prostate cancer phenotype and patient prognosis in a tissue microarray containing more than 3200 prostate cancers. SNP array analysis of 72 prostate cancers revealed a small deletion at 3p13 in 14 (19%) of the tumours, including the putative tumour suppressors FOXP1, RYBP and SHQ1. FISH analysis using FOXP1-specific probes revealed deletions in 16.5% and translocations in 1.2% of 1828 interpretable cancers. 3p13 deletions were linked to adverse features of prostate cancer, including advanced stage (p < 0.0001), high Gleason grade (p = 0.0125), and early PSA recurrence (p = 0.0015). In addition, 3p13 deletions were linked to ERG+ cancers and to PTEN deletions (p < 0.0001 each). A subset analysis of ERG+ tumours revealed that 3p13 deletions occurred independently from PTEN deletions (p = 0.3126), identifying tumours with 3p13 deletion as a distinct molecular subset of ERG+ cancers. mRNA expression analysis confirmed that all 3p13 genes were down regulated by the deletion. Ectopic over-expression of FOXP1, RYBP and SHQ1 resulted in decreased colony-formation capabilities, corroborating a tumour suppressor function for all three genes. In summary, our data show that deletion of 3p13 defines a distinct and aggressive molecular subset of ERG+ prostate cancers, which is possibly driven by inactivation of multiple tumour suppressors. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

No AccessJournal of UrologyAdult Urology1 Feb 2009Nomogram Predicting the Probability of Early Recurrence After Radical Prostatectomy for Prostate Cancer Jochen Walz, Felix K.-H. Chun, Eric A. Klein, Alwyn Reuther, Fred Saad, Markus Graefen, Hartwig Huland, and Pierre I. Karakiewicz Jochen WalzJochen Walz Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Canada Department of Urology, Institut Paoli-Calmettes, Marseille, France Supported by the Grant of the Vereinigung Norddeutscher Urologen. More articles by this author , Felix K.-H. ChunFelix K.-H. Chun Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author , Eric A. KleinEric A. Klein Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author , Alwyn ReutherAlwyn Reuther Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author , Fred SaadFred Saad Department of Urology, University of Montreal, Montreal, Canada More articles by this author , Markus GraefenMarkus Graefen Martini Clinic–Prostate Cancer Center, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author , Hartwig HulandHartwig Huland Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany Martini Clinic–Prostate Cancer Center, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Canada Department of Urology, University of Montreal, Montreal, Canada Supported by the University of Montreal Heath Center Urology Associates, Fonds de la Recherche en Santé du Québec, the University of Montreal Department of Surgery and the University of Montreal Health Center (CHUM) Foundation. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.10.033AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We developed a nomogram predicting the probability of early biochemical recurrence after radical prostatectomy because early recurrence predisposes to distant metastasis and prostate cancer related mortality. Identifying patients at risk for early recurrence may improve prognosis as early institution of adjuvant therapy may reduce the risk of progression. Materials and Methods: From January 1992 to December 2005, 2,911 patients underwent radical prostatectomy for localized prostate cancer. Cox regression models addressing biochemical recurrence after radical prostatectomy were used to identify significant predictors. Age, prostate specific antigen, pathological Gleason sum, surgical margin, extracapsular extension, seminal vesicle invasion and lymph node invasion were considered. A nomogram predicting the probability of biochemical recurrence-free survival within 2 years after radical prostatectomy was developed. Data from an independent center were used for external validation (2,875). Results: In both cohorts combined during the first 2 years 11.0% (639) of all patients experienced relapse which accounted for 58.5% of all observed biochemical recurrence. In the development cohort except for age all covariates represented significant predictors of biochemical recurrence after radical prostatectomy. Pathological Gleason sum 7 or greater, seminal vesicle invasion and lymph node invasion were the most powerful predictors of biochemical recurrence. The accuracy (c-index) of the nomogram predicting biochemical recurrence-free survival within 2 years after radical prostatectomy was 0.82 in the external validation cohort. Conclusions: Two-thirds of all instances of relapse occur during the first 2 years after radical prostatectomy. Those patients can be highly accurately identified with our nomogram. They might benefit the most from adjuvant treatment and could be the ideal candidates for adjuvant treatment trials. References 1 : Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol2002; 167: 528. Link, Google Scholar 2 : 25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series. J Urol2006; 176: 569. 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Google Scholar 14 : Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Natl Cancer Inst2006; 98: 715. Google Scholar 15 : Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology2001; 58: 843. Google Scholar 16 : Early endocrine therapy versus radical prostatectomy combined with early endocrine therapy for stage D1 prostate cancer. Br J Urol1997; 79: 226. Google Scholar 17 : Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy. Urology2001; 57: 1033. Google Scholar 18 Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial: The Medical Research Council Prostate Cancer Working Party Investigators Group. Br J Urol1997; 79: 235. Google Scholar 19 : Current controversies in the treatment of high-risk prostate cancer. Curr Opin Urol2008; 18: 263. Google Scholar 20 : Anatomic radical retropubic prostatectomy-long-term recurrence-free survival rates for localized prostate cancer. World J Urol2006; 24: 273. Google Scholar © 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited byTan N, Shen L, Khoshnoodi P, Alcalá H, Yu W, Hsu W, Reiter R, Lu D and Raman S (2017) Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount HistopathologyJournal of Urology, VOL. 199, NO. 5, (1218-1223), Online publication date: 1-May-2018.Adam M, Hannah A, Budäus L, Steuber T, Salomon G, Michl U, Haese A, Fisch M, Wittmer C, Steurer S, Minner S, Heinzer H, Huland H, Graefen M, Sauter G, Schlomm T and Isbarn H (2014) A Tertiary Gleason Pattern in the Prostatectomy Specimen and its Association with Adverse Outcome after Radical ProstatectomyJournal of Urology, VOL. 192, NO. 1, (97-102), Online publication date: 1-Jul-2014.Budäus L, Isbarn H, Eichelberg C, Lughezzani G, Sun M, Perrotte P, Chun F, Salomon G, Steuber T, Köllermann J, Sauter G, Ahyai S, Zacharias M, Fisch M, Schlomm T, Haese A, Heinzer H, Huland H, Montorsi F, Graefen M and Karakiewicz P (2010) Biochemical Recurrence After Radical Prostatectomy: Multiplicative Interaction Between Surgical Margin Status and Pathological StageJournal of Urology, VOL. 184, NO. 4, (1341-1346), Online publication date: 1-Oct-2010.Morote J, del Amo J, Borque A, Ars E, Hernández C, Herranz F, Arruza A, Llarena R, Planas J, Viso M, Palou J, Raventós C, Tejedor D, Artieda M, Simón L, Martínez A and Rioja L (2010) Improved Prediction of Biochemical Recurrence After Radical Prostatectomy by Genetic PolymorphismsJournal of Urology, VOL. 184, NO. 2, (506-511), Online publication date: 1-Aug-2010.Wright J, Dalkin B, True L, Ellis W, Stanford J, Lange P and Lin D (2010) Positive Surgical Margins at Radical Prostatectomy Predict Prostate Cancer Specific MortalityJournal of Urology, VOL. 183, NO. 6, (2213-2218), Online publication date: 1-Jun-2010.Kuroiwa K, Shiraishi T, Ogawa O, Usami M, Hirao Y and Naito S (2010) Discrepancy Between Local and Central Pathological Review of Radical Prostatectomy SpecimensJournal of Urology, VOL. 183, NO. 3, (952-957), Online publication date: 1-Mar-2010. Volume 181Issue 2February 2009Page: 601-608 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsrecurrenceprostatectomynomogramsprognosisprostatic neoplasmsMetricsAuthor Information Jochen Walz Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Canada Department of Urology, Institut Paoli-Calmettes, Marseille, France Supported by the Grant of the Vereinigung Norddeutscher Urologen. More articles by this author Felix K.-H. Chun Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author Eric A. Klein Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author Alwyn Reuther Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author Fred Saad Department of Urology, University of Montreal, Montreal, Canada More articles by this author Markus Graefen Martini Clinic–Prostate Cancer Center, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author Hartwig Huland Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany Martini Clinic–Prostate Cancer Center, University Medical Centre Eppendorf, Hamburg, Germany More articles by this author Pierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Canada Department of Urology, University of Montreal, Montreal, Canada Supported by the University of Montreal Heath Center Urology Associates, Fonds de la Recherche en Santé du Québec, the University of Montreal Department of Surgery and the University of Montreal Health Center (CHUM) Foundation. More articles by this author Expand All Advertisement PDF downloadLoading ...

Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa). Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies. IBX (≥10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement. PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model. Any PCa and HGPCa were diagnosed in 46% (n = 318) and 20% (n = 137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p < 0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p < 0.001). Accuracy was increased by 4.5–7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤30%, only a few patients with HGPCa (≤2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted. The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario.

Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo.To investigate ZA for the prevention of BMs in high-risk localised PCa.Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10.Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr.BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups.A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients.ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr.Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr.The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the ISRCTN register at http://www.controlled-trials.com/ISRCTN66626762.

Therapy (outcomes research).2b. What's known on the subject? and What does the study add? Historically, surgeons were reluctant to perform radical prostatectomy (RP) in LN positive disease. Nowadays, a shift towards multimodal treatment strategies in such patients, comprising RP with extended lymph node dissection followed by radiation and/or hormonal therapy can be detected. However, this change of paradigm is not supported by evidence derived from treatment guidelines. Retrospective studies on this topic, comprising small numbers of patients from the pre-PSA era in the US suggest a survival advantage, if RP is performed. Our analyses of cancer control rates between patients with discontinued vs. completed prostatectomy revealed a superior clinical progression free- and cancer specific-survival rate in those patients with completed prostatectomy. These results add knowledge on treatment outcome of a current patient population since previous retrospective studies include patients from the pre-PSA era.To assess the prognostic role of radical prostatectomy (RP) in lymph node (LN) positive patients with prostate cancer (PCa) in a contemporary RP cohort.Between 1992 and 2004, 158 consecutive patients with clinically localized PCa and regional LN metastasis were identified. Fifty patients underwent LN dissection and discontinued RP, combined with early hormonal therapy (HT) (RP-), whereas, in 108 patients, RP was completed followed by adjunctive HT (RP+). Clinical progression-free- (CPFS) and cancer-specific survival (CSS) were studied using Kaplan-Meier analysis. Disease characteristics and the impact of RP on CPFS and CSS were further assessed using Cox proportional hazard models. A matched pair analysis between RP- and RP+ patients was performed based on clinical and pathological factors.Median follow-up was 98 months (interquartile range, 88-113). Five- and 10-year CPFS was 77% and 61% for RP+ patients vs 61% and 31%, for RP- patients (P=0.005), respectively. A similar trend was observed for CSS (84% and 76% for RP+ vs 81% and 46% for RP-; P=0.001). Type of treatment (RP- vs RP+) and number of positive LN were multivariate predictors of CPFS and CSS (all P≤0.05). In the matched pair analyses, RP+ patients showed superior CPFS and CSS (P<0.005).RP had a beneficial impact, resulting in the superior survival of patients with LN positive PCa after controlling for LN tumour burden in a contemporary RP series. The findings obtained in the present study support the role of RP as an important component of multimodal strategies of LN positive PCa.

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? The widespread use of PSA testing resulted in a stage migration towards clinical organ‐confined prostate cancers at diagnosis during the last decade. However, our study of a large cohort demonstrates an increasing proportion of patients with non‐organ confined cancers after radical prostatectomy. These findings may be related to the introduction of new, non‐established treatment options for low‐risk prostate cancer patients during the last years and the growing adoption of RP in a multimodal treatment setting for locally advanced tumours. OBJECTIVE • To investigate the stage migration patterns during the last decade in European men treated with radical prostatectomy (RP). PATIENTS AND METHODS • Between 2000 and 2009, RP was performed in 8916 patients at a single European tertiary‐care institution. • Age at diagnosis, clinical and pathological data were prospectively collected, and trends and proportions of preoperative and pathological findings were analysed over time. RESULTS • The median (mean) age of patients increased from 62 (62) to 63 (65) years between 2000 and 2009 ( P &lt; 0.001). • When patients were stratified based on their clinical findings according to the D’Amico risk groups for disease progression, the proportion of low‐risk patients dropped from 66% in 2004 to 35% ( P = 0.016) in the final year of the study period. • Similarly, histopathological evaluation of RP specimens showed a decrease of favourable disease (organ confinement and Gleason 3 + 3 grade) from 53 to 17% ( P = 0.008). • This trend was accompanied by an increase in the number of patients with non‐organ‐confined prostate cancer (PCa) from 19% in 2003 to 33% in 2009 ( P = 0.008). • The restriction of the analyses in the present study to a single tertiary‐care centre could limit the generalizeability of the results. CONCLUSIONS • During the last decade, we observed an inverse stage migration trend in those European patients with PCa who were treated with RP. • The recorded increase in patients with non‐organ‐confined disease after RP could be related to changes in patient selection and the growing adoption of RP in multimodal treatment settings for locally advanced tumours as well as the availability of new treatment alternatives for low‐risk disease.

Cell-mediated immunity may impact prostate cancer progression and has great therapeutic potential. Here, we investigated the clinical significance of the numeric density of regulatory T cells (Tregs) in prostate cancer as the presence of such cells in the tumour microenvironment has been linked to clinical outcome in other tumour entities. We detected Tregs by FOXP3 immunohistochemistry in 88.8% of 2002 prostate cancer specimens in tissue microarray format, the largest cohort so far in which Tregs have been quantified. The density of Tregs in tumour tissue was compared with pathological parameters and clinical outcome. The number of Tregs identified per 0.6mm tissue spot ranged from 1 to 10 in normal and 1 to 103 FOXP3+ cells in tumour samples. Prostate-specific antigen (PSA) recurrence-free survival was significantly reduced in patients with higher numbers of Tregs (p=0.0151). Further, a higher number of intratumoural FOXP3+ Tregs was associated with a more advanced tumour stage (p=0.0355) and higher Ki67 labelling index (p<0.0001). The tissue density of Tregs was unrelated to other clinical parameters such as spread to lymph nodes, preoperative PSA level and Gleason score. Our study suggests that the intratumoural presence of regulatory T cells may have substantial functional impact and may confer an adverse clinical course in prostate cancer.

Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. Within the Surveillance, Epidemiology and End Results database (2004–2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n = 474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32–0.50) versus NLT (n = 1896). In MVA CRR after PSM, RP (n = 161) results in lower CSM (SHR 0.59, 95% CI 0.35–0.99) versus RT (n = 161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR = 5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy.

The benefit of intraoperative neurovascular structure-adjacent frozen section examination (NeuroSAFE) of the prostate was demonstrated in open radical prostatectomy. In da Vinci robot-assisted prostatectomy (DVP), this approach is often avoided due to suspected difficulties in harvesting the prostate, loss in pneumoperitoneum, increased blood loss, and prolonged operating room (OR) time.To provide a detailed description of the technique, feasibility, and impact of the NeuroSAFE technique on OR time, blood loss, frequency of nerve sparing (NS), and positive surgical margins (PSMs) in DVP.We analyzed 1570 consecutive patients undergoing DVP from 2004 to 2012. NeuroSAFE was performed in 1178 patients.The prostate was intraoperatively harvested via an extension of the camera trocar incision without undocking the robotic arms. Blood spillage from the dorsal vein complex due to the loss of pneumoperitoneum was avoided by upward traction on the transurethral catheter. After prostate removal, pneumoperitoneum was reestablished by closing the extended incision with running sutures and repositioning the optical trocar. The NeuroSAFE procedure consisted of intraoperative bilateral frozen sections covering the entire neurovascular bundles adjacent prostate surface.We compared OR time, blood loss, NS frequency, and PSMs in non-NeuroSAFE versus NeuroSAFE DVP.There was no significant difference in blood loss (253.5 ± 204.4 ml vs 265.8 ± 246.7 ml; p=0.49) and OR time (220 min ± 51 vs 224 min ± 64; p=0.22). No complications associated with specimen harvesting occurred. NS rate increased significantly with versus without NeuroSAFE (overall 97% vs 81%; pT2 99% vs 90%, pT3a 94% vs 74%, pT3b 91% vs 30). PSM rate dropped significantly with NeuroSAFE (overall 16% vs 24%; pT2 8% vs 15%, pT3a 22% vs 39%, pT3b 49% vs 67%; all p<0.05).We demonstrate a time-efficient and safe adaption of the NeuroSAFE technique to DVP.We describe a feasible and secure adaption of the neurovascular structure-adjacent frozen section examination (NeuroSAFE) procedure for da Vinci robot-assisted prostatectomy. We showed that there was no increased blood loss and operating room time. We maximized the nerve-sparing frequency and could reduce positive surgical margins even in non-organ-confined tumors.

Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high-level and 8.7% with low-level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high-level p53 immunostaining, but only 3% (1 of 31) low-level p53 cases carried putative dominant-negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low-level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low-level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining—most likely accompanying dominant negative or oncogenic p53 mutation—has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.

Evaluation of treatment options for localized prostate cancer (PCa) remains among the highest priorities for comparative effectiveness research. Surgery and radiotherapy (RT) are the two interventions most commonly used.To provide a critical narrative review of evidence of the comparative effectiveness and harms of surgery and RT in the treatment of localized PCa.A collaborative critical narrative review of the literature was conducted.Evidence to clearly guide treatment choice in PCa remains insufficient. Randomized trials are underpowered for clinically meaningful endpoints and have demonstrated no difference in overall or PCa-specific survival. Observational studies have consistently demonstrated an absolute survival benefit for men treated with radical prostatectomy, but are limited by selection bias and residual confounding errors. Surgery and RT are associated with comparable health-related quality of life following treatment in three randomized trials. Randomized data regarding urinary, erectile, and bowel function show few long-term (>5 yr) differences, although short-term continence and erectile function were worse following surgery and short-term urinary bother and bowel function were worse following RT. There has been recent recognition of other complications that may significantly affect the life trajectory of those undergoing PCa treatment. Of these, hospitalization, the need for urologic, rectoanal, and other major surgical procedures, and secondary cancers are more common among men treated with RT. Androgen deprivation therapy, frequently co-administered with RT, may additionally contribute to treatment-related morbidity. Technological innovations in surgery and RT have shown inconsistent oncologic and functional benefits.Owing to underpowered randomized control studies and the selection biases inherent in observational studies, the question of which treatment provides better PCa control cannot be definitively answered now or in the near future. Complications following PCa treatment are relatively common regardless of treatment approach. These include the commonly identified issues of urinary incontinence and erectile dysfunction, and others including hospitalization and invasive procedures to manage complications and secondary malignancies. Population-based outcome studies, rather than clinical trial data, will be necessary for a comprehensive understanding of the relative benefits and risks of each therapeutic approach.Surgery and radiotherapy are the most common interventions for men diagnosed with prostate cancer. Comparisons of survival after these treatments are limited by various flaws in the relevant studies. Complications are common regardless of the treatment approach.

The impact of cytoreductive radical prostatectomy (CRP) on oncological outcomes in patients with prostate cancer (PCa) and distant metastases has been demonstrated by retrospective data with their potential selection bias. Using prospective institutional data, we compared the outcomes between 43 PCa patients with low-volume bone metastases (1–3 lesions) undergoing CRP (median follow-up 32.7 mo) and 40 patients receiving best systemic therapy (BST; median follow-up 82.2 mo). The inclusion criteria for both cohorts were identical. So far, no significant difference in castration resistant–free survival (p = 0.92) or overall survival (p = 0.25) has been detected. Compared to recent reports, the outcomes for our control group are more favorable, indicating a potential selection bias in the previous retrospective studies. Therefore, the unclear oncological effect has to be weighed against the potential risks of CRP. However, patients benefit from a significant reduction in locoregional complications (7.0% vs 35%; p < 0.01) when undergoing CRP. Patient summary In this study we analyzed the impact of surgery in patients with prostate cancer and bone metastases. Using prospective data, we could not show a significant benefit of surgery on survival, but the rate of locoregional complications was lower. Therefore, patients should be treated within prospective trials evaluating the role of cytoreductive prostatectomy in low-volume, bone metastatic prostate cancer.

Persistent prostate-specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). To investigate the impact of persistent PSA at 6 wk after RP on long-term oncologic outcomes and to assess patient characteristics associated with persistent PSA. Within a high-volume center database we identified patients who harbored persistent (≥0.1 ng/ml) versus undetectable PSA (<0.1 ng/ml) at 6 wk after RP. Patients with neo- and/or adjuvant androgen-deprivation therapy (ADT) were excluded. Logistic regression models tested for prediction of persistent PSA. Kaplan–Meier analyses and Cox regression models tested the effect of persistent PSA on metastasis-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS) rates. Propensity score matching (PSM) was performed to test the impact of salvage radiotherapy (SRT) on OS and CSS in patients with persistent PSA. Of 11 604 identified patients, 8.8% (n = 1025) harbored persistent PSA. At 15 yr after RP, MFS, OS, and CSS were 53.0% versus 93.2% (p < 0.001), 64.7% versus 81.2% (p < 0.001), and 75.5% versus 96.2% (p < 0.001) for persistent versus undetectable PSA, respectively. In multivariable Cox regression models, persistent PSA represented an independent predictor for metastasis (hazard ratio [HR]: 3.59, p < 0.001), death (HR: 1.86, p < 0.001), and cancer-specific death (HR: 3.15, p < 0.001). SRT was associated with improved OS (HR: 0.37, p = 0.02) and CSS (HR: 0.12, p < 0.01) after 1:1 PSM. Main limitation is missing data on postoperative PSA and duration of salvage ADT. Persistent PSA is associated with worse oncologic outcome after RP, namely, metastasis, death, and cancer-specific death. In patients with persistent PSA, SRT resulted in improved OS and CSS. We assessed the impact of persistent prostate-specific antigen (PSA) at 6 wk after radical prostatectomy on oncologic outcomes. Early persistent PSA was associated with worse metastasis-free survival, overall survival, and cancer-specific survival. Salvage radiotherapy may result in a survival benefit in well-selected patients.

Objective To compare oncological, functional and surgical outcomes of open retropubic radical prostatectomy (ORP) vs robot‐assisted laparoscopic radical prostatectomy (RARP). Patients and methods We identified 10 790 consecutive treated patients within our prospective database (2008–2016) who underwent either ORP (7007 patients) or RARP (3783). All procedures were performed by seven highly trained surgeons performing both surgical approaches regularly. Oncological (48‐month biochemical recurrence [BCR] rate), functional (urinary continence, erectile function), and surgical outcomes (rate of nerve‐sparing [NS] procedures, lymph node yield, surgical margin [SM] status, length of hospital stay [LOS], operation time, blood loss, transfusion rate, time to catheter removal) were assessed. Kaplan–Meier, multivariable Cox and logistic regression models were used to test for BCR and functional outcome differences. Results No statistically significant difference regarding oncological outcome distinguished between ORP vs RARP. For functional outcomes, the 1‐week continence rates were higher in the ORP group (25.8% vs 21.8%, P &lt; 0.001). At 3 months, no statistically significant differences were observed. At 12 months, continence rates were modestly higher in the RARP group (90.3% vs 88.8%, P = 0.01). This effect was no longer observed after stratification for age‐groups. The 12‐month potency rates were similar in ORP vs RARP (80.3% vs 83.6%, P = 0.33). For surgical outcomes, there was no significant difference in the rates of NS procedures, lymph node yield, SM status, and LOS. Conversely, operation time was shorter in ORP, and blood loss, transfusion rates and time to catheter removal were significantly lower in RARP. Conclusions Both surgical approaches, performed in a high‐volume centre by the same surgeons, achieve excellent, comparable oncological and functional outcomes. However, a modest advantage for RARP for surgical outcomes was observed, most likely attributable to its minimally invasive nature, and better teaching capabilities. Consequently, more than the surgical approach itself, the well‐trained surgeon remains the most important factor to achieve satisfactory outcomes.

The impact of biochemical recurrence (BCR) after radical treatment of prostate cancer on oncological outcomes remains unclear. A new European Association of Urology BCR risk stratification (low and high risk) has been proposed. To validate these risk groups, we retrospectively analyzed data for 1125 post-radical prostatectomy (RP) BCR patients (surgery between 1992 and 2006). Univariable Kaplan-Meier plots and multivariable Cox regression models with time-dependent covariates were used to test the independent predictor status of the risk grouping on metastatic progression (MP) and prostate cancer-specific mortality (PCSM). The 5-yr MP-free and PCSM-free survival rates were significantly higher among patients with low BCR risk compared to their high-risk counterparts. In multivariable analyses, the BCR risk grouping reached independent predictor status for MP (hazard ratio [HR] 3.46; p < 0.001) and PCSM (HR 5.12; p < 0.001). Salvage radiation therapy, especially when delivered at prostate-specific antigen <0.5 ng/ml, was highly protective. Our findings corroborate the validity of this novel BCR risk grouping, which is easily applicable in daily practice and could be valuable in decision-making for salvage therapy and clinical trials. The European Association of Urology grouping for the risk of biochemical recurrence of prostate cancer after radical prostatectomy was valid when applied in a European study cohort.

<h3>Importance</h3> It is unknown how treatment with radical prostatectomy (RP) and adjuvant external beam radiotherapy (EBRT), androgen deprivation therapy (ADT), or both (termed<i>MaxRP</i>) compares with treatment with EBRT, brachytherapy, and ADT (termed<i>MaxRT</i>). <h3>Objective</h3> To investigate whether treatment of Gleason score 9-10 prostate cancer with MaxRP vs MaxRT was associated with prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM) risk. <h3>Design, Setting, and Participants</h3> The study cohort comprised 639 men with clinical T1-4,N0M0 biopsy Gleason score 9-10 prostate cancer. Between February 6, 1992, and April 26, 2013, a total of 80 men were consecutively treated with MaxRT at the Chicago Prostate Cancer Center, and 559 men were consecutively treated with RP and pelvic lymph node dissection at the Martini-Klinik Prostate Cancer Center. Follow-up started on the day of prostate EBRT or RP and concluded on October 27, 2017. <h3>Exposures</h3> Of the 559 men managed with RP and pelvic lymph node dissection, 88 (15.7%) received adjuvant EBRT, 49 (8.8%) received ADT, and 50 (8.9%) received both. <h3>Main Outcomes and Measures</h3> Treatment propensity score–adjusted risk of PCSM and ACM and the likelihood of equivalence of these risks between treatments using a plausibility index. <h3>Results</h3> The cohort included 639 men, with a mean (SD) age of 65.83 (6.52) years. After median follow-ups of 5.51 years (interquartile range, 2.19-6.95 years) among 80 men treated with MaxRT and 4.78 years (interquartile range, 4.01-6.05 years) among 559 men treated with RP-containing treatments, 161 men had died, 106 (65.8%) from prostate cancer. There was no significant difference in the risk of PCSM (adjusted hazard ratio, 1.33; 95% CI, 0.49-3.64;<i>P</i> = .58) and ACM (adjusted hazard ratio, 0.80; 95% CI, 0.36-1.81;<i>P</i> = .60) when comparing men who underwent MaxRP vs MaxRT, with plausibility indexes for equivalence of 76.75% for the end point of the risk of PCSM and 77.97% for the end point of the risk of ACM. Plausibility indexes for all other treatment comparisons were less than 63%. <h3>Conclusions and Relevance</h3> Results of this study suggest that it is plausible that treatment with MaxRP or MaxRT for men with biopsy Gleason score 9-10 prostate cancer can lead to equivalent risk of PCSM and ACM.

Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility.We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy.After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04).Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.

In 651 patients mapping of the prostate by 6 systematic sextant ultrasonography guided biopsies was performed without major side effects using the automatic biopsy gun. The histological findings provided data on patients with normal and abnormal prostates as determined by digital rectal examination. Only 3 of 72 nonurological patients (4%) with normal prostate specific antigen (PSA) levels of less than 4 ng./ml. had prostate cancer. Of the 259 patients with a firm prostate on digital rectal examination 105 (41%) had prostate cancer. For those with a PSA level of less than 4 and 4 ng./ml. or greater the positive biopsy rates were 13% and 58%, respectively. Of 56 patients with clinical stage B or C disease and a PSA level of less than 4 ng./ml. 20 (36%) had prostate cancer, compared to 155 of 187 (83%) with a PSA level of 4 ng./ml. or greater. Transrectal ultrasound was not helpful in screening for prostate cancer due to the low positive biopsy rate for hypoechoic lesions. However, among 175 patients with clinical stage B or C disease transrectal ultrasound identified 157 (90%) with prostate cancer.

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Mar 2001A VALIDATED STRATEGY FOR SIDE SPECIFIC PREDICTION OF ORGAN CONFINED PROSTATE CANCER: A TOOL TO SELECT FOR NERVE SPARING RADICAL PROSTATECTOMY MARKUS GRAEFEN, ALEXANDER HAESE, UWE PICHLMEIER, PETER G. HAMMERER, JOACHIM NOLDUS, KATHARINA BUTZ, ANDREAS ERBERSDOBLER, ROLF-PETER HENKE, UWE MICHL, SALVATOR FERNANDEZ, and HARTWIG HULAND MARKUS GRAEFENMARKUS GRAEFEN , ALEXANDER HAESEALEXANDER HAESE , UWE PICHLMEIERUWE PICHLMEIER , PETER G. HAMMERERPETER G. HAMMERER , JOACHIM NOLDUSJOACHIM NOLDUS , KATHARINA BUTZKATHARINA BUTZ , ANDREAS ERBERSDOBLERANDREAS ERBERSDOBLER , ROLF-PETER HENKEROLF-PETER HENKE , UWE MICHLUWE MICHL , SALVATOR FERNANDEZSALVATOR FERNANDEZ , and HARTWIG HULANDHARTWIG HULAND View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)66544-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. Materials and Methods: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. Results: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. Conclusions: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy. References 1 : Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate1983; 4: 473. Crossref, Medline, Google Scholar 2 : Return of erections and urinary continence following nerve sparing radical prostatectomy. J Urol1993; 150: 905. Abstract, Google Scholar 3 : Patient-reported complications and follow-up treatment after radical prostatectomy. The national Medicare experience: 1988–1990 (updated 1993). Urology1993; 42: 622. Google Scholar 4 : Nerve sparing radical prostatectomy: a different view. J Urol1995; 154: 145. 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Google Scholar From the Department of Urology and Institutes of Mathematics and Computer Science in Medicine, and Pathology University Hospital Eppendorf, Hamburg, Germany© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byRecabal P, Assel M, Musser J, Caras R, Sjoberg D, Coleman J, Mulhall J, Parra R, Scardino P, Touijer K, Eastham J and Laudone V (2016) Erectile Function Recovery after Radical Prostatectomy in Men with High Risk FeaturesJournal of Urology, VOL. 196, NO. 2, (507-513), Online publication date: 1-Aug-2016.von Bodman C, Brock M, Roghmann F, Byers A, Löppenberg B, Braun K, Pastor J, Sommerer F, Noldus J and Palisaar R (2013) Intraoperative Frozen Section of the Prostate Decreases Positive Margin Rate While Ensuring Nerve Sparing Procedure During Radical ProstatectomyJournal of Urology, VOL. 190, NO. 2, (515-520), Online publication date: 1-Aug-2013.Lavery H, Prall D and Abaza R (2011) Active Patient Decision Making Regarding Nerve Sparing During Radical Prostatectomy: A Novel ApproachJournal of Urology, VOL. 186, NO. 2, (487-493), Online publication date: 1-Aug-2011.Löppenberg B, Noldus J, Holz A and Palisaar R (2010) Reporting Complications After Open Radical Retropubic Prostatectomy Using the Martin CriteriaJournal of Urology, VOL. 184, NO. 3, (944-948), Online publication date: 1-Sep-2010.Nakanishi H, Troncoso P and Babaian R (2008) Prediction of Extraprostatic Extension in Men With Biopsy Gleason Score of 8 or GreaterJournal of Urology, VOL. 180, NO. 6, (2441-2446), Online publication date: 1-Dec-2008.Michl U, Friedrich M, Graefen M, Haese A, Heinzer H and Huland H (2018) Prediction of Postoperative Sexual Function After Nerve Sparing Radical Retropubic ProstatectomyJournal of Urology, VOL. 176, NO. 1, (227-231), Online publication date: 1-Jul-2006.Steuber T, Graefen M, Haese A, Erbersdobler A, Chun F, Schlom T, Perrotte P, Huland H and Karakiewicz P (2018) Validation of a Nomogram for Prediction of Side Specific Extracapsular Extension at Radical ProstatectomyJournal of Urology, VOL. 175, NO. 3, (939-944), Online publication date: 1-Mar-2006.KAMAT A, JACOBSOHN K, TRONCOSO P, SHEN Y, WEN S and BABAIAN R (2018) VALIDATION OF CRITERIA USED TO PREDICT EXTRAPROSTATIC CANCER EXTENSION: A TOOL FOR USE IN SELECTING PATIENTS FOR NERVE SPARING RADICAL PROSTATECTOMYJournal of Urology, VOL. 174, NO. 4 Part 1, (1262-1265), Online publication date: 1-Oct-2005.HAESE A, VAISANEN V, LILJA H, KATTAN M, RITTENHOUSE H, PETTERSSON K, CHAN D, HULAND H, SOKOLL L and PARTIN A (2018) COMPARISON OF PREDICTIVE ACCURACY FOR PATHOLOGICALLY ORGAN CONFINED CLINICAL STAGE T1c PROSTATE CANCER USING HUMAN GLANDULAR KALLIKREIN 2 AND PROSTATE SPECIFIC ANTIGEN COMBINED WITH CLINICAL STAGE AND GLEASON GRADEJournal of Urology, VOL. 173, NO. 3, (752-756), Online publication date: 1-Mar-2005.TSUZUKI T, HERNANDEZ D, AYDIN H, TROCK B, WALSH P and EPSTEIN J (2018) PREDICTION OF EXTRAPROSTATIC EXTENSION IN THE NEUROVASCULAR BUNDLE BASED ON PROSTATE NEEDLE BIOPSY PATHOLOGY, SERUM PROSTATE SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATIONJournal of Urology, VOL. 173, NO. 2, (450-453), Online publication date: 1-Feb-2005.OHORI M, KATTAN M, KOH H, MARU N, SLAWIN K, SHARIAT S, MURAMOTO M, REUTER V, WHEELER T and SCARDINO P (2018) Predicting the Presence and Side of Extracapsular Extension: A Nomogram for Staging Prostate CancerJournal of Urology, VOL. 171, NO. 5, (1844-1849), Online publication date: 1-May-2004.NAYA Y, SLATON J, TRONCOSO P, OKIHARA K and BABAIAN R (2018) Tumor Length and Location of Cancer on Biopsy Predict for Side Specific Extraprostatic Cancer ExtensionJournal of Urology, VOL. 171, NO. 3, (1093-1097), Online publication date: 1-Mar-2004.KAOUK J, DESAI M, ABREU S, PAPAY F and GILL I (2018) Robotic Assisted Laparoscopic Sural Nerve Grafting During Radical Prostatectomy: Initial ExperienceJournal of Urology, VOL. 170, NO. 3, (909-912), Online publication date: 1-Sep-2003.FREEDLAND S, ARONSON W, TERRIS M, KANE C, AMLING C, DOREY F and PRESTI J (2018) Percent of Prostate Needle Biopsy Cores With Cancer is Significant Independent Predictor of Prostate Specific Antigen Recurrence Following Radical Prostatectomy: Results From SEARCH DatabaseJournal of Urology, VOL. 169, NO. 6, (2136-2141), Online publication date: 1-Jun-2003.SHAH O, ROBBINS D, MELAMED J and LEPOR H (2018) The New York University Nerve Sparing Algorithm Decreases the Rate of Positive Surgical Margins Following Radical Retropubic ProstatectomyJournal of Urology, VOL. 169, NO. 6, (2147-2152), Online publication date: 1-Jun-2003.Elliott S, Shinohara K, Logan S and Carroll P (2018) Sextant Prostate Biopsies Predict Side and Sextant Site of Extracapsular Extension of Prostate CancerJournal of Urology, VOL. 168, NO. 1, (105-109), Online publication date: 1-Jul-2002. Volume 165Issue 3March 2001Page: 857-863 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsprostatic neoplasmsbiopsyprostatectomyprostateprostate-specific antigenMetricsAuthor Information MARKUS GRAEFEN More articles by this author ALEXANDER HAESE More articles by this author UWE PICHLMEIER More articles by this author PETER G. HAMMERER More articles by this author JOACHIM NOLDUS More articles by this author KATHARINA BUTZ More articles by this author ANDREAS ERBERSDOBLER More articles by this author ROLF-PETER HENKE More articles by this author UWE MICHL More articles by this author SALVATOR FERNANDEZ More articles by this author HARTWIG HULAND More articles by this author Expand All Advertisement PDF downloadLoading ...

To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP.The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading.Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%.Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Improved selection criteria have lead to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localised prostate cancer (PCA). Patient questionnaire based outcome analysis on post-operative erectile function after uni- or bilateral nerve-sparing RRP is described.Between January 1992 and March 1999, 366 patients (mean age 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. Indication for nerve-sparing procedure was based on the results of a multivariate classification and regression tree analysis (CART). For evaluation of post-operative patient-reported rates of sexual and erectile function non-validated and validated questionnaires (IIEF 5) were administered after a follow-up of 12 months. Data of five operation periods were analysed.The unilateral procedure resulted in rates of 13-29% of erections sufficient for unassisted intercourse. Some degree of tumescence was reported by 37-73% of the remaining patients. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3-5, only four patients of period 2 received the bilateral procedure. Here, rates of erections sufficient for intercourse were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. Patients with grades 4 and 5 erections had IIEF scores of 19.2 and 20.2 and patients without rigidity or tumescence had scores of 5.7 and 7.0 after uni- and bilateral nerve-sparing procedure, respectively. Patients <60 years of age had better erections than those > or =60 (unilateral: 19% versus 13%, bilateral 45% versus 38%).Compared to a unilateral nerve-sparing procedure, the bilateral nerve-sparing technique revealed much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse without use of sexual aids.

No AccessJournal of UrologyInvestigative Urology1 Sep 2004A SIDE BY SIDE COMPARISON OF CYTOLOGY AND BIOMARKERS FOR BLADDER CANCER DETECTION GRETHCHEN L. SCHROEDER, MARIA-FERNANDA LORENZO-GOMEZ, STEFAN H. HAUTMANN, MARTIN G. FRIEDRICH, SINAN EKICI, HARTWIG HULAND, and VINATA LOKESHWAR GRETHCHEN L. SCHROEDERGRETHCHEN L. SCHROEDER , MARIA-FERNANDA LORENZO-GOMEZMARIA-FERNANDA LORENZO-GOMEZ , STEFAN H. HAUTMANNSTEFAN H. HAUTMANN , MARTIN G. FRIEDRICHMARTIN G. FRIEDRICH , SINAN EKICISINAN EKICI , HARTWIG HULANDHARTWIG HULAND , and VINATA LOKESHWARVINATA LOKESHWAR View All Author Informationhttps://doi.org/10.1097/01.ju.0000134347.14643.abAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borlänger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine. Materials and Methods: A total of 138 urine specimens from 115 patients were collected at University Hospital Hamburg-Eppendorf, including 59 with active bladder cancer and 79 with a history of bladder cancer (73) or with benign genitourinary conditions (6). Specimens were assayed by the HA-HAase test, BTA-Stat, Hemastix (hemoglobin dipstick) and UBC-Rapid. Cystoscopy and histological findings were used to make the clinical diagnosis. Cytology results were available on 92 patients. Results: In a side by side comparison the HA-HAase test, cytology, BTA-Stat, Hemastix and UBC-Rapid had 88.1%, 70.6%, 52.5%, 50.8% and 35.6% sensitivity, and 81%, 81%, 76.7%, 78.2% and 75% specificity, respectively. The accuracy, and negative and positive predictive values of the HA-HAase test were the highest (84.1%, 90.1% and 77.6%), followed by cytology (77.2%, 82.5% and 68.6%), Hemastix (66.4%, 67.8% and 63.8%), BTA-Stat (66.2%, 67.8% and 63.3%) and UBC-Rapid (57.8%, 60% and 52.5%), respectively. Conclusions: The HA-HAase test is superior to cytology, BTA-Stat, Hemastix and UBC-Rapid for detecting bladder cancer recurrence. A side-by-side comparison of tumor markers should help identify a marker for monitoring bladder cancer recurrence. References 1 : Cost-effectiveness of a modified care protocol substituting bladder tumor markers for cystos-copy for the followup of patients with transitional cell carcinoma of the bladder: a decision analytical approach. J Urol2002; 167: 75. Link, Google Scholar 2 : Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses. Urology2003; 61: 109. Google Scholar 3 : Current bladder tumor tests: does their projected utility fulfill clinical necessity?. J Urol2001; 165: 1067. Link, Google Scholar 4 : New diagnostic strategies in the detection and staging of bladder cancer. Curr Opin Urol2003; 13: 351. Google Scholar 5 : Can hematuria be a predictor as well as a symptom or sign of bladder cancer?. Cancer Epidemiol Biomarkers Prev1996; 5: 993. Google Scholar 6 : Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. Am Fam Physician2001; 63: 1145. Google Scholar 7 : Complement factor H or a related protein is a marker for transitional cell cancer of the bladder. Clin Cancer Res1998; 4: 2511. Google Scholar 8 : The application of human complement factor H-related protein (BTA TRAK) in monitoring patients with bladder cancer. Urol Clin North Am2000; 27: 63. Google Scholar 9 : Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence. J Urol2002; 167: 80. Link, Google Scholar 10 : Urinary bladder cancer test: a new urinary tumor marker in the follow-up of superficial bladder cancer. Urology2000; 56: 787. Google Scholar 11 : Qualitative and quantitative detection of urinary human complement factor H-related protein (BTA stat and BTA TRAK) and fragments of cytokeratins 8, 18 (UBC rapid and UBC IRMA) as markers for transitional cell carcinoma of the bladder. Eur Urol2002; 41: 34. Google Scholar 12 : Comparison of the monoclonal UBC-ELISA test and the NMP22 ELISA test for the detection of urothelial cell carcinoma of the bladder. Urology2000; 55: 223. Google Scholar 13 : Diagnostic performance of the urinary bladder carcinoma antigen ELISA test and multiparametric DNA/cytokeratin flow cytometry in urine voided samples from patients with bladder carcinoma. Cancer2001; 92: 2811. Google Scholar 14 : Hyaluronan: a multifunctional, megaDalton, stealth molecule. Curr Opin Cell Biol2000; 12: 581. Google Scholar 15 : The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol2001; 20: 499. Google Scholar 16 : Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells. J Biol Chem2000; 275: 27641. Google Scholar 17 : Elevated tissue expression of hyaluronic acid and hyaluronidase validates the HA-HAase urine test for bladder cancer. J Urol2001; 165: 2068. Link, Google Scholar 18 : Urinary hyaluronic acid and hyaluronidase: markers for bladder cancer detection and evaluation of grade. J Urol2000; 163: 348. Link, Google Scholar 19 : Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid-hyaluronidase and BTA-Stat tests. Cancer2002; 95: 61. Google Scholar 20 : Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev1994; 3: 439. Google Scholar 21 : Hematuria home screening: repeat testing results. J Urol1995; 154: 57. Link, Google Scholar From the Departments of Urology (GLS, M-FL-G, SE, VL) and Cell Biology and Anatomy (VL) and Sylvester Comprehensive Cancer Center (VL), University of Miami School of Medicine, Miami, Florida, and Department of Urology, University Hospital Hamburg-Eppendorf, University of Hamburg (SHH, MGF, HH), Hamburg, Germany© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byNarayan V, Adejoro O, Schwartz I, Ziegelmann M, Elliott S and Konety B (2017) The Prevalence and Impact of Urinary Marker Testing in Patients with Bladder CancerJournal of Urology, VOL. 199, NO. 1, (74-80), Online publication date: 1-Jan-2018.Gomez C, Gomez P, Knapp J, Jorda M, Soloway M and Lokeshwar V (2009) Hyaluronic Acid and HYAL-1 in Prostate Biopsy Specimens: Predictors of Biochemical RecurrenceJournal of Urology, VOL. 182, NO. 4, (1350-1356), Online publication date: 1-Oct-2009.Nieder A, MacKinnon J, Huang Y, Fleming L, Koniaris L and Lee D (2007) Florida Bladder Cancer Trends 1981 to 2004: Minimal Progress in Decreasing Advanced DiseaseJournal of Urology, VOL. 179, NO. 2, (491-495), Online publication date: 1-Feb-2008.Sarosdy M, Kahn P, Ziffer M, Love W, Barkin J, Abara E, Jansz K, Bridge J, Johansson S, Persons D and Gibson J (2018) Use of a Multitarget Fluorescence In Situ Hybridization Assay to Diagnose Bladder Cancer in Patients With HematuriaJournal of Urology, VOL. 176, NO. 1, (44-47), Online publication date: 1-Jul-2006. Volume 172Issue 3September 2004Page: 1123-1126 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsbladder neoplasmstumor markers, biologicalhematuriabladdercytologyMetricsAuthor Information GRETHCHEN L. SCHROEDER Equal study contribution. More articles by this author MARIA-FERNANDA LORENZO-GOMEZ Equal study contribution. More articles by this author STEFAN H. HAUTMANN More articles by this author MARTIN G. FRIEDRICH More articles by this author SINAN EKICI More articles by this author HARTWIG HULAND More articles by this author VINATA LOKESHWAR More articles by this author Expand All Advertisement PDF downloadLoading ...

We present a randomised, parallel group, multicentre phase 4 trial comparing short- and long-term chemoprophylaxis with Mitomycin C (MMC) with short-term immunoprophylaxis with Bacillus Calmette-Guérin (BCG) after transurethral resection of the bladder for non-muscle-invasive bladder carcinoma.Four hundred ninety-five patients with intermediate- to high-risk non-muscle-invasive bladder cancer (recurrent and/or multifocal pTaG1, TaG2-3, and T1G1-3) were randomised to BCG RIVM 2 x 10(8) CFU weekly for 6 wk, MMC 20 mg weekly for 6 wk, or MMC 20 mg weekly for 6 wk followed by monthly instillations for 3 yr.The 3-yr recurrence-free rates were 65.5% (95%CI, 55.9-73.5%) for short-term BCG, and 68.6% (59.9-75.7%) for short-term MMC, whereas recurrence-free rates were significantly increased to 86.1% (77.9-91.4%) in patients with MMC long-term therapy (log-rank test, p=0.001).Long-term MMC significantly reduced the risk of tumour recurrence without enhanced toxicity compared with both short-term BCG and MMC in patients with intermediate- and high-risk non-muscle-invasive bladder carcinoma. Our data provide a rationale for maintenance intravesical chemotherapy in this population.

Abstract BACKGROUND Men who undergo radical prostatectomy (RP) are at long‐term risk of biochemical recurrence (BCR). In this report, the authors have described a model capable of predicting BCR up to at least 15 years after RP that can adjust predictions according to the disease‐free interval. METHODS Cox regression was used to model the probability of BCR (a prostate‐specific antigen level &gt;0.1 ng/mL and rising) in 601 men who underwent RP with a median follow‐up of 11.4 years. The statistical significance of nomogram predictors was confirmed with a competing‐risks regression model. The model was validated internally with 200 bootstraps and externally at 5 years, 10 years, and 15 years in 2 independent cohorts of 2963 and 3178 contemporary RP patients from 2 institutions. RESULTS The 5‐year, 10‐year, 15‐year, and 20‐year actuarial rates of BCR‐free survival were 84.8%, 71.2%, 61.1%, and 58.6%, respectively. Pathologic stage, surgical margin status, pathologic Gleason sum, type of RP, and adjuvant radiotherapy represented independent predictors of BCR in both Cox and competing‐risks regression models and constituted the nomogram predictor variables. In internal validation, the nomogram accuracy was 79.3%, 77.2%, 79.7%, and 80.6% at 5 years, 10 years, 15 years, and 20 years, respectively, after RP. In external validation, the nomogram was 77.4% accurate at 5 years in the first cohort and 77.9%, 79.4%, and 86.3% accurate at 5 years, 10 years, and 15 years, respectively, in the second cohort. CONCLUSIONS Patients who undergo RP remain at risk of BCR beyond 10 years after RP. The nomogram described in this report distinguishes itself from other tools by its ability to accurately predict the conditional probability of BCR up to at least 15 years after surgery. Cancer 2008. © 2008 American Cancer Society.

To test the accuracy of a previously externally validated sextant biopsy nomogram in referred men exposed to > or =10 or more biopsy cores. Moreover, we explored the hypothesis that a more accurate predictive tool could be developed.Previous nomogram predictors (age, digital rectal examination, prostate-specific antigen, and percent free PSA) were used to assess the accuracy of our previous nomogram in a cohort consisting of 2900 men referred for prostatic evaluation. Moreover, these variables were complemented with sampling density (SD) (i.e., ratio of gland volume and the number of planned biopsy cores) within multivariable logistic regression models (LRM) predicting presence of prostate cancer (pCA) on the initial 10 or more core biopsy. The LRMs were used to develop and internally validate (200 bootstrap resamples) a new nomogram in 1162 men from Hamburg, Germany. The LRMs' external validity was tested in three separate cohorts (Hamburg, n=582; Milan, n=961; Seattle, n=195).The contemporary external validation of the previously validated sextant nomogram demonstrated 70% accuracy. Internal validation of the new nomogram demonstrated 77% accuracy, and external cohorts demonstrated 73-76% accuracy.In the era of extended biopsy schemes, previously developed predictive models are less accurate in predicting the probability of pCA on initial biopsy. We developed a new tool that allows obtaining more accurate predictions. Moreover, before biopsy, it also allows defining the ideal ratio between gland volume and the number of planned biopsy cores that would yield the ideal biopsy rate.

To evaluate several methods of predicting prostate cancer-related outcomes, i.e. nomograms, look-up tables, artificial neural networks (ANN), classification and regression tree (CART) analyses and risk-group stratification (RGS) models, all of which represent valid alternatives.We present four direct comparisons, where a nomogram was compared to either an ANN, a look-up table, a CART model or a RGS model. In all comparisons we assessed the predictive accuracy and performance characteristics of both models.Nomograms have several advantages over ANN, look-up tables, CART and RGS models, the most fundamental being a higher predictive accuracy and better performance characteristics.These results suggest that nomograms are more accurate and have better performance characteristics than their alternatives. However, ANN, look-up tables, CART analyses and RGS models all rely on methodologically sound and valid alternatives, which should not be abandoned.

No AccessJournal of UrologyAdult urology1 Jul 2006Prediction of Postoperative Sexual Function After Nerve Sparing Radical Retropubic Prostatectomyis accompanied byErectile Dysfunction a Decade Later: Another Paradigm Shift Uwe H.G. Michl, Martin G. Friedrich, Markus Graefen, Alexander Haese, Hans Heinzer, and Hartwig Huland Uwe H.G. MichlUwe H.G. Michl Equal study contribution. More articles by this author , Martin G. FriedrichMartin G. Friedrich Equal study contribution. More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Alexander HaeseAlexander Haese More articles by this author , Hans HeinzerHans Heinzer More articles by this author , and Hartwig HulandHartwig Huland More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(06)00632-XAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Preservation of sexual function is one of the main objectives in radical prostatectomy. We assessed possible predictive factors for postoperative sexual function including preoperative International Index of Erectile Function score, age and extent of nerve sparing procedures for more precise preoperative counseling of patients undergoing radical prostatectomy. Materials and Methods: Between January 2000 and December 2001 a total of 694 patients with clinically organ confined prostate cancer underwent nerve sparing radical prostatectomy. Preoperative erectile function was assessed with the International Index of Erectile Function score. After at least 12 months of followup patients were asked to answer the International Index of Erectile Function and Quality of Life Questionnaire C 30 via mail. Results: A total of 411 patients responded to the questionnaire, 122 of whom underwent unilateral nerve sparing radical prostatectomy and 289 underwent bilateral nerve sparing radical prostatectomy. Data on preoperative and postoperative International Index of Erectile Function scores were available for 389 patients. Data on the International Index of Erectile Function and the postoperative Quality of Life Questionnaire C 30 were available for 382 patients. The median decrease in International Index of Erectile Function score was 7 points. Patients undergoing unilateral nerve sparing radical prostatectomy had a significantly stronger decrease in International Index of Erectile Function score compared to patients undergoing the bilateral nerve sparing procedure (12 vs 6 points). Preoperative International Index of Erectile Function score and extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) were significantly associated with better postoperative sexual function whereas age was not. Based on preoperative International Index of Erectile Function score, surgical technique and age, the likelihood of postoperative satisfactory erectile function can be defined preoperatively. Conclusions: We confirmed the impact of the extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) and highlighted the effect of preoperative erectile function as measured by the International Index of Erectile Function and age at surgery on postoperative sexual function. Our data can be used for counseling patients undergoing radical nerve sparing prostatectomy regarding recovery of erectile function. References 1 : Anatomic radical prostatectomy: evolution of the surgical technique. J Urol1998; 160: 2418. Link, Google Scholar 2 : Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J Urol1990; 143: 538. Link, Google Scholar 3 : A catalog of prostate cancer nomograms. J Urol2001; 165: 1562. Link, Google Scholar 4 : Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer. Urology2001; 58: 393. Google Scholar 5 : A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy. J Urol2001; 165: 857. Link, Google Scholar 6 : Patient-reported sexual function after nerve-sparing radical retropubic prostatectomy. Eur Urol2002; 42: 118. Google Scholar 7 : Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol1991; 145: 998. Link, Google Scholar 8 : Contemporary results of anatomic radical prostatectomy. CA Cancer J Clin1999; 49: 282. Google Scholar 9 : Defining sexual outcomes after treatment for localized prostate carcinoma. Cancer2002; 95: 1773. Google Scholar 10 : Histologic differentiation, cancer volume, and pelvic lymph node metastasis in adenocarcinoma of the prostate. Cancer1990; 66: 1225. Google Scholar 11 : Histologic grading of prostate cancer: a perspective. Hum Pathol1992; 23: 273. Google Scholar 12 : Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res1999; 11: 319. Google Scholar 13 : Stage migration in clinically localized prostate cancer. Eur Urol2000; 38: 74. Google Scholar 14 : Potency, continence and complications in 3,477 consecutive radical retropubic prostatectomies. J Urol2004; 172: 2227. Link, Google Scholar 15 : Nerve-sparing radical retropubic prostatectomy. Results of a patient survey. Urologe A2001; 40: 102. Google Scholar 16 : Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology2000; 55: 58. Google Scholar 17 : Factors predicting recovery of erections after radical prostatectomy. J Urol2000; 164: 1929. Link, Google Scholar 18 : Nerve sparing radical prostatectomy: a different view. J Urol1995; 154: 145. Link, Google Scholar 19 : Nerve-sparing laparoscopic radical prostatectomy: replicating the open surgical technique. Urology2004; 64: 123. Google Scholar 20 : Long-term results of the Stamey bladder neck suspension procedure: a patient questionnaire based outcome analysis. J Urol1997; 157: 1672. Link, Google Scholar Department of Urology, University of Hamburg, University Hospital Hamburg-Eppendorf, Germany© 2006 by American Urological AssociationFiguresReferencesRelatedDetailsCited byTreiyer A, Anheuser P, Bütow Z and Steffens J (2018) A Single Center Prospective Study: Prediction of Postoperative General Quality of Life, Potency and Continence After Radical Retropubic ProstatectomyJournal of Urology, VOL. 185, NO. 5, (1681-1685), Online publication date: 1-May-2011.Sievert K, Hennenlotter J, Laible I, Amend B, Nagele U and Stenzl A (2018) The Commonly Performed Nerve Sparing Total Prostatectomy Does Not Acknowledge the Actual Nerve CoursesJournal of Urology, VOL. 181, NO. 3, (1076-1081), Online publication date: 1-Mar-2009.Marien T, Sankin A and Lepor H (2018) Factors Predicting Preservation of Erectile Function in Men Undergoing Open Radical Retropubic ProstatectomyJournal of Urology, VOL. 181, NO. 4, (1817-1822), Online publication date: 1-Apr-2009.Levinson A, Pavlovich C, Ward N, Link R, Mettee L and Su L (2018) Association of Surgeon Subjective Characterization of Nerve Sparing Quality With Potency Following Laparoscopic Radical ProstatectomyJournal of Urology, VOL. 179, NO. 4, (1510-1514), Online publication date: 1-Apr-2008.Walz J, Perrotte P, Gallina A, Bénard F, Valiquette L, McCormack M, Montorsi F and Karakiewicz P (2018) Ejaculatory Disorders May Affect Screening for Prostate CancerJournal of Urology, VOL. 178, NO. 1, (232-238), Online publication date: 1-Jul-2007.Related articlesJournal of Urology9 Nov 2018Erectile Dysfunction a Decade Later: Another Paradigm Shift Volume 176Issue 1July 2006Page: 227-231 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordsimpotencequality of lifesexual behaviorprostatectomyquestionnairesMetricsAuthor Information Uwe H.G. Michl Equal study contribution. More articles by this author Martin G. Friedrich Equal study contribution. More articles by this author Markus Graefen More articles by this author Alexander Haese More articles by this author Hans Heinzer More articles by this author Hartwig Huland More articles by this author Expand All Advertisement PDF downloadLoading ...

There is increasing evidence for the role of epigenetic gene silencing in superficial bladder cancer. The aim of the current study was to investigate the prognostic value of epigenetic alterations in patients with non-muscle invasive bladder carcinoma. We checked the methylation status of 20 cancer associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H-TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-Cadherin, ICAM-1, TIMP-3, MLH-1, COX-2) for DNA methylation. We analysed microdissected tumour samples from 105 consecutive patients with primary non-muscle invasive bladder carcinoma. Quantitative methylation analysis of CpG sites in the promoter region of the genes was performed with methylation sensitive quantitative real time PCR (‘Methylight’). Univariate analysis for association with tumour recurrence was carried out with the Kaplan–Meier analysis and the log-rank test. Follow-up data were available in 95/105 patients (91.4%). A tumour recurrence was observed in 26 patients (27.3%). We could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-Cadherin), where methylation was associated with tumour recurrence. In Kaplan–Meier analysis, TIMP-3 showed a significant association with recurrence free survival. Methylation of TIMP-3 predicted prolonged disease free interval. In this study, we report a comprehensive analysis on prognostic relevance of gene methylation in non-muscle invasive bladder cancer. We identified one gene (TIMP-3) where methylation was associated with a more favourable outcome. Our data strongly support the usefulness of gene methylation as a prognostic marker in patients with non-muscle invasive bladder cancer.

Active surveillance (AS) represents a treatment option for select patients with low-risk, organ-confined prostate cancer (PCa). In this report, the authors addressed the rates of misclassification associated with the use of 5 different clinical criteria for AS. Misclassification was defined as the presence of either nonorgan-confined disease or high-grade PCa.Between 1992 and 2007, 4885 patients underwent radical prostatectomy (RP) at 1 of 2 European academic centers, and the patients were identified who fulfilled the criteria for AS according to 5 different investigational groups (Hardie et al, Roemeling et al, Choo et al, Klotz, and D'Amico and Coleman). Statistics targeted the rates of misclassification for each of the 5 definitions.Four thousand three hundred eight patients, 4047 patients, 3993 patients, 2455 patients, and 2345 patients fulfilled the AS criteria of Hardie et al, Roemeling et al, Choo et al, Klotz, and D'Amico and Coleman, respectively. Extracapsular extension was reported in 13.5% to 26% of patients, and seminal vesicle invasion was reported in 2.9% to 8.2% of patients. When PCa with Gleason scores from 8 to 10 at RP was considered high grade, the misclassification rates were 27%, 25%, 25%, 15%, and 14% for the 5 studies, respectively. Conversely, when PCa with Gleason scores from 7 to 10 was considered high grade, the misclassification rates increased to 56%, 55%, 45%, 42%, and 39%, respectively.The currently available AS criteria are limited by a high rate of misclassification. The use of more selective AS criteria may reduce the rate of misclassification but also may reduce significantly the percentage of patients who may be considered for AS.

To evaluate whether nerve-sparing procedure itself is a risk factor for biochemical recurrence in carefully selected patients.We compared patients of our historical series who in retrospect were candidates for nerve-sparing (NS) procedure with a contemporary cohort of patients. With respect to stage migration and selection bias between these two groups we performed a multivariate analysis adjusting for all explanatory variables in the model. NS was performed in n = 723 patients (bilateral n = 359, unilateral n = 364) in comparison to n = 620 patients undergoing non-NS RP, comprising n = 756 patients within the favorable pT2 category. We examined the association of clinical and histopathological parameters in relation to PSA recurrence in uni- and multivariate analyses including NS as a variable. Furthermore, for each prostate lobe separately we determined whether surgical procedure (nerve-sparing vs. non-nerve-sparing RP) resulted in a positive margin.In univariate analysis there was no difference in pT2 (log rank p = 0.091), pT3a (log rank p = 0.171) and pT3b (log rank p = 0.110) cancers between patients treated with NS compared to non-NS surgery. The 3- and 5-year recurrence free survival rate for patients with pT2, pT3a and pT3b cancers treated by NS vs. non-NS were 96.3/94.9 vs. 94.9/90.8, 75.0/61.8 vs. 73.4/55.0 and 46/30 vs. 38/23. Multivariate regression analysis showed no association with PSA failure (p = 0.798) for patients who underwent NS. Capsular penetration (p < 0.001), lymph-node status (p < 0.001), seminal vesicle invasion (p < 0.001), surgical margin status (p = 0.0130), Gleason score (p < 0.001) and preoperative PSA (p = 0.005) were significantly associated with risk of failure. The positive margin rate per each prostate lobe in pT2 cancers was 6.5% vs. 5.1% in NS and non-NS cases, 10.3% vs. 17.3% in patients with extracapsular extension and 15.0% vs. 25.1% in cases with seminal vesicle invasion respectively.NS RP is an oncologically safe procedure provided that appropriate preoperative selection of patients by means of a validated nomogram is performed. Moreover, evaluation of positive margins in patients undergoing NS and non-NS RP revealed no evidence that adequacy of tumor excision is compromised by NS procedure.

To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH).In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias.Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%.Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection.

By differential quantitative protein expression, it has previously been shown that annexin A3 (ANXA3) expression is associated with prostate cancer. However little is known about the role and biology of ANXA3 in the human prostate. The aim of this study was to thoroughly analyze ANXA3 expression patterns and its potential as a prognostic marker in a large set of benign, preneoplastic, and neoplastic prostate tissue samples. Immunohistochemistry-based ANXA3 protein expression was analyzed for 1589 prostate cancers as well as smaller subsets of benign epithelium and high-grade prostatic intraepithelial neoplasia (PIN) in a tissue microarray format. All samples of benign prostatic epithelium and PIN showed ANXA3 protein expression, with PIN lesions showing a decreased staining intensity compared with benign epithelium (p < 0.0001). In cancer, ANXA3 protein expression was essentially reduced, resulting in a negative staining rate of 27.2%, which correlated with increasing pT stage and Gleason score (p < 0.0001). ANXA3 status in cancer was shown to be an independent adverse prognostic factor and enabled substratification of the large group of intermediate-risk patients (n = 969) into high- and low-risk subgroups. ANXA3 represents a promising candidate tissue marker, and when combined with the standard prognostic parameters, is suggested to provide a more precise prediction of prognosis in the individual patient, therefore harboring the potential to contribute to future patient management.

No AccessJournal of Urology1 Jul 1984Long-Term Mitomycin C Instillation After Transurethral Resection of Superficial Bladder Carcinoma: Influence on Recurrence, Progression and Survival H. Huland, U. Otto, M. Droese, and G. Klöppel H. HulandH. Huland More articles by this author , U. OttoU. Otto More articles by this author , M. DroeseM. Droese More articles by this author , and G. KlöppelG. Klöppel More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)49449-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail In a prospective controlled study the influence of long-term mitomycin C instillation therapy on tumor recurrence, progression and patient survival after transurethral resection of superficial bladder tumors was evaluated. This report is an update of a randomized controlled study that was stopped 1.5 years ago. The results show that long-term mitomycin C instillation therapy improves recurrence rate, progression rate and survival in patients with superficial bladder cancer. © 1984 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByRose A, El-Leithy T, Dorp F, Zakaria A, Eisenhardt A, Tschirdewahn S and Rübben H (2018) Mistletoe Plant Extract in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Phase Ib/IIa Single Group Dose Escalation StudyJournal of Urology, VOL. 194, NO. 4, (939-943), Online publication date: 1-Oct-2015.Lee E, Schwaibold H, Fradet Y, Huland E and Huland H (2018) Tumor-Associated Antigens in Normal Mucosa of Patients With Superficial Transitional Cell Carcinoma of the BladderJournal of Urology, VOL. 157, NO. 3, (1070-1073), Online publication date: 1-Mar-1997.Vegt P, Witjes J, Witjes W, Doesburg W, Debruyne F, van der Meijden A and Crawford E (2018) Original Articles: Bladder Cancer: A Randomized Study of Intravesical Mitomycin C, Bacillus Calmette-Guerin Tice and Bacillus Calmette-Guerin RIVM Treatment in pTa-pT1 Papillary Carcinoma and Carcinoma in Situ of the BladderJournal of Urology, VOL. 153, NO. 3S, (929-933), Online publication date: 1-Mar-1995.Bouffioux C, Kurth K, Bono A, Oosterlinck W, Kruger C, De Pauw M and Sylvester R (2018) Original Articles: Bladder Cancer: Intravesical Adjuvant Chemotherapy for Superficial Transitional Cell Bladder Carcinoma: Results of 2 European Organization for Research and Treatment of Cancer Randomized Trials With Mitomycin C and Doxorubicin Comparing Early Versus Delayed Instillations and Short-Term Versus Long-Term TreatmentJournal of Urology, VOL. 153, NO. 3S, (934-941), Online publication date: 1-Mar-1995.Bouffioux C, Denis L, Oosterlinck W, Viggiano G, Vergison B, Keuppens F, De Pauw M, Sylvester R and Cheuvart B (2018) Adjuvant Chemotherapy of Recurrent Superficial Transitional Cell Carcinoma: Results of a European Organization for Research on Treatment of Cancer Randomized Trial Comparing Intravesical Instillation of Thiotepa, Doxorubicin and CisplatinJournal of Urology, VOL. 148, NO. 2 Part 1, (297-301), Online publication date: 1-Aug-1992.Heinzer H, Huland E, Mönk M and Huland H (2018) Distribution of 486P 3/12 Antigen, Abo(H) Blood Group Antigen and T Antigen in Cystectomy Specimens from Patients with Stage T2 Transitional Cell Carcinoma of the BladderJournal of Urology, VOL. 148, NO. 3 Part 1, (802-805), Online publication date: 1-Sep-1992.Klän R, Loy V and Huland H (2018) Residual Tumor Discovered in Routine Second Transurethral Resection in Patients with Stage T1 Transitional Cell Carcinoma of the BladderJournal of Urology, VOL. 146, NO. 2 Part 1, (316-318), Online publication date: 1-Aug-1991.Huland H, Klöppel G, Feddersen I, Otto U, Brachmann W, Hubmann H, Kaufmann J, Knipper W, Lantzius-Beninga F and Huland E (2018) Comparison of Different Schedules of Cytostatic Intravesical Instillations in Patients with Superficial Bladder Carcinoma: Final Evaluation of a Prospective Multicenter Study with 419 PatientsJournal of Urology, VOL. 144, NO. 1, (68-71), Online publication date: 1-Jul-1990.Ratliff T (2018) Editorial CommentsJournal of Urology, VOL. 144, NO. 1, (71-71), Online publication date: 1-Jul-1990.Huland E, Huland H and Schneider A (2018) Quantitative Immunocytology in the Management of Patients with Superficial bladder Carcinoma. I. A Marker to Identify Patients Who do not Require ProphylaxisJournal of Urology, VOL. 144, NO. 3, (637-639), Online publication date: 1-Sep-1990.Droller M (2018) Editorial CommentsJournal of Urology, VOL. 144, NO. 3, (639-639), Online publication date: 1-Sep-1990.Oyasu R (2018) Editorial CommentsJournal of Urology, VOL. 144, NO. 3, (639-640), Online publication date: 1-Sep-1990.Soloway M (2018) Editorial CommentsJournal of Urology, VOL. 144, NO. 1, (71-72), Online publication date: 1-Jul-1990.Drago P, Badalament R, Lucas J and Drago J (2018) Bladder Wall Calcification after Intravesical Mitomycin C Treatment of Superficial Bladder CancerJournal of Urology, VOL. 142, NO. 4, (1071-1072), Online publication date: 1-Oct-1989.Soloway M (2018) Editorial CommentJournal of Urology, VOL. 142, NO. 4, (1072-1072), Online publication date: 1-Oct-1989.Kim H and Lee C (2018) Intravesical Mitomycin C Instillation as a Prophylactic Treatment of Superficial Bladder TumorJournal of Urology, VOL. 141, NO. 6, (1337-1339), Online publication date: 1-Jun-1989. (2018) Reply by AuthorsJournal of Urology, VOL. 142, NO. 4, (1072-1072), Online publication date: 1-Oct-1989.Heney N, Koontz W, Barton B, Soloway M, Trump D, Hazra T and Weinstein R (2018) Intravesical Thiotepa versus Mitomycin C in Patients with TA, T1 and TIS Transitional Cell Carcinoma of the Bladder: A Phase III Prospective Randomized StudyJournal of Urology, VOL. 140, NO. 6, (1390-1393), Online publication date: 1-Dec-1988.Jurincic C, Engelmann U, Gasch J and Klippel K (2018) Immunotherapy in Bladder Cancer with Keyhole-Limpet Hemocyanin: A Randomized StudyJournal of Urology, VOL. 139, NO. 4, (723-726), Online publication date: 1-Apr-1988.Smith A, Vitale P, Lowe B and Woodside J (2018) Treatment of Superficial Papillary Transitional Cell Carcinoma of the Ureter by Vesicoureteral Reflux of Mitomycin CJournal of Urology, VOL. 138, NO. 5, (1231-1233), Online publication date: 1-Nov-1987.Herr H, Laudone V and Whitmore W (2018) An Overview of Intravesical Therapy for Superficial Bladder TumorsJournal of Urology, VOL. 138, NO. 6, (1363-1368), Online publication date: 1-Dec-1987.Huland H, Arndt R, Huland E, Loening T and Steffens M (2018) Monoclonal Antibody 486 P 3/12: A Valuable Bladder Carcinoma Marker for ImmunocytologyJournal of Urology, VOL. 137, NO. 4, (654-659), Online publication date: 1-Apr-1987.Kelley D, Ratliff T, Catalona W, Shapiro A, Lage J, Bauer W, Haaff E and Dresner S (2018) Intravesical Bacillus Calmette-Guerin Therapy for Superficial Bladder Cancer: Effect of Bacillus Calmette-Guerin Viability on Treatment ResultsJournal of Urology, VOL. 134, NO. 1, (48-53), Online publication date: 1-Jul-1985.Huland H, Otto U and Paleske A (2018) Chemotherapy and Human Bladder Carcinoma Transplanted into NMRI NU/NU MiceJournal of Urology, VOL. 134, NO. 3, (601-606), Online publication date: 1-Sep-1985.Soloway M (2018) Treatment of Superficial Bladder Cancer with Intravesical Mitomycin C: Analysis of Immediate and Long-Term Response in 70 PatientsJournal of Urology, VOL. 134, NO. 6, (1107-1109), Online publication date: 1-Dec-1985.Zincke H, Benson R, Hilton J and Taylor W (2018) Intravesical Thiotepa and Mitomycin C Treatment Immediately After Transurethral Resection and Later for Superficial (Stages Ta and Tis) Bladder Cancer: A Prospective, Randomized, Stratified Study with Crossover DesignJournal of Urology, VOL. 134, NO. 6, (1110-1113), Online publication date: 1-Dec-1985. Volume 132Issue 1July 1984Page: 27-29 Advertisement Copyright & Permissions© 1984 by The American Urological Association Education and Research, Inc.MetricsAuthor Information H. Huland More articles by this author U. Otto More articles by this author M. Droese More articles by this author G. Klöppel More articles by this author Expand All Advertisement Loading ...

What’s known on the subject? and What does the study add? Circulating tumour cells (CTC) have prognostic relevance for patients with different metastatic carcinomas. Detection of CTC using the CellSearch system has also been reported in bladder cancer, but mainly in patients with metastatic disease. This is the largest report demonstrating that detection of CTC in non‐metastatic bladder cancer patients is feasible using the CellSearch system. Presence of CTC may be predictive for early systemic disease. OBJECTIVE To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non‐metastatic, advanced bladder cancer (NMABC). PATIENTS AND METHODS Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy. Detection of CTC was performed using the USA Food and Drug Administration‐approved CellSearch TM system. Data were compared with the clinical and histopathological findings. RESULTS CTC were detected in 15 of 50 patients (30%) with non‐metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1–372; median: 2). In non‐metastatic patients, the mean number of CTC was 3.1 (range: 1–11; median: 1). Except for a univariate association between CTC with vessel infiltration ( P = 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection. A median 1‐year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC‐positive patients died as a result of cancer progression. CTC‐positive patients showed significantly worse overall ( P = 0.001), progression‐free ( P &lt; 0.001) and cancer specific survival ( P &lt; 0.001) compared to preoperatively CTC‐negative patients. CONCLUSION This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearch TM system. Our findings suggest that the presence of CTC may be predictive for early systemic disease.

To date, few data are available about the sequential use of the tyrosine kinase inhibitors (TKI) sorafenib and sunitinib in metastatic renal cell carcinoma (mRCC). To investigate the effectiveness of the use of sunitinib after progression under sorafenib in mRCC. A retrospective analysis of 30 patients with progressive mRCC, treated with sorafenib between May 2005 and February 2008. When radiologic progression was diagnosed, treatment was switched to sunitinib and continued until a further tumour progression occurred. Radiologic evaluation of the treatment results was performed every 3 mo according to the criteria for Response Evaluation Criteria in Solid Tumors (RECIST). Adverse effects and therapeutic abnormalities (eg, dose reduction) were documented during regular visits. Of the patients, 50% benefited from the secondary use of sunitinib. In detail, a radiologically confirmed new disease stabilisation or partial response was observed in seven and eight patients, respectively. Median progression-free survival was 8.7 mo and 10.3 mo under sorafenib and sunitinib, respectively. Overall, the median time from the initialisation of the first TKI until progression under therapy with the second TKI was 17.3 mo. To our knowledge, this is the second largest study reporting results of sequential therapy from sorafenib followed by sunitinib. However, the number of patients is still not extensive enough to settle this important question conclusively. This study supports the hypothesis that sequential TKI therapy with the sorafenib followed by sunitinib has clinical validity in some patients with advanced renal cell carcinoma when progressive disease occurs under the initial TKI therapy.

No AccessJournal of Urology1 Aug 1984Tumor Cell Deoxyribonucleic Acid Content and Prognosis in Human Renal Cell Carcinoma U. Otto, H. Baisch, H. Huland, and G. Klöppel U. OttoU. Otto More articles by this author , H. BaischH. Baisch More articles by this author , H. HulandH. Huland More articles by this author , and G. KlöppelG. Klöppel More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)49576-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Flow cytometry was used to study tumor tissue from 68 patients with stages I to III renal cell carcinoma who were followed for 1 to 4 years. Results of flow cytometry correlated extremely well with the clinical course of the patients: 21 per cent of those with diploid tumor cells had metastases during the interval of observation, compared to 89 per cent of those with aneuploid tumor cells. We concluded that flow cytometry helps to identify at the time of radical nephrectomy patients who are most likely to suffer recurrent tumor and, therefore, are candidates for early chemotherapy. If nuclear grading is applied in addition to flow cytometry the rates of false positive and false negative results in respect to prediction of prognosis are reduced to 3 and 14 per cent, respectively. © 1984 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLjungberg B, Larsson P, Roos G, Stenling R and Wilson G (2018) Cell Kinetics of Renal Cell Carcinoma Studied with in Vivo Iododeoxyuridine Incorporation and Flow CytometryJournal of Urology, VOL. 151, NO. 6, (1509-1513), Online publication date: 1-Jun-1994.van der Poel H, Schaafsma H, Vooijs G, Debruyne F and Schalken J (2018) Quantitative Light Microscopy in Urological OncologyJournal of Urology, VOL. 148, NO. 1, (1-13), Online publication date: 1-Jul-1992.Ljungberg B, Larsson P, Stenling R and Roos G (2018) Flow Cytometric Deoxyribonucleic Acid Analysis in Stage I Renal Cell CarcinomaJournal of Urology, VOL. 146, NO. 3, (697-699), Online publication date: 1-Sep-1991.Ring K, Burbige K, Benson M, Karp F and Hensle T (2018) The Flow Cytometric Analysis of Undescended Testes in ChildrenJournal of Urology, VOL. 144, NO. 2 Part 2, (494-498), Online publication date: 1-Aug-1990.Currin S, Lee S and Walther P (2018) Flow Cytometric Assessment of Deoxyribonucleic Acid Content in Renal Adenocarcinoma: Does Ploidy Status Enhance Prognostic Stratification Over Stage Alone?Journal of Urology, VOL. 143, NO. 3, (458-463), Online publication date: 1-Mar-1990.Murphy G, Partin A, Maygarden S and Mohler J (2018) Nuclear Shape Analysis for Assessment of Prognosis in Renal Cell CarcinomaJournal of Urology, VOL. 143, NO. 6, (1103-1107), Online publication date: 1-Jun-1990.Boyle E, Reiman H, Kramer S, Kelalis P, Rainwater L and Lieber M (2018) Embryonal Rhabdomyosarcoma of Bladder and Prostate: Nuclear DNA Patterns Studied by Flow CytometryJournal of Urology, VOL. 140, NO. 5 Part 2, (1119-1121), Online publication date: 1-Nov-1988.Winkler H and Lieber M (2018) Primary Squamous Cell Carcinoma of the Male Urethra: Nuclear Deoxyribonucleic Acid Ploidy Studied by Flow CytometryJournal of Urology, VOL. 139, NO. 2, (298-303), Online publication date: 1-Feb-1988.Ljungberg B, Duchek M, Hietala S, Roos G and Stenling R (2018) Renal Cell Carcinoma in a Solitary Kidney: Late Nephrectomy after 35 Years and Analysis of Tumor Deoxyribonucleic Acid ContentJournal of Urology, VOL. 139, NO. 2, (350-352), Online publication date: 1-Feb-1988.Rainwater L, Hosaka Y, Farrow G, Kramer S, Kelalis P and Lieber M (2018) Wilms Tumors: Relationship of Nuclear Deoxyribonucleic Acid Ploidy to Patient SurvivalJournal of Urology, VOL. 138, NO. 4 Part 2, (974-977), Online publication date: 1-Oct-1987.Rainwater L, Hosaka Y, Farrow G and Lieber M (2018) Well Differentiated Clear Cell Renal Carcinoma: Significance of Nuclear Deoxyribonucleic Acid Patterns Studied by Flow CytometryJournal of Urology, VOL. 137, NO. 1, (15-20), Online publication date: 1-Jan-1987.Murphy W (2018) Editorial CommentJournal of Urology, VOL. 137, NO. 1, (20-20), Online publication date: 1-Jan-1987.Eble J and Sledge G (2018) Cellular Deoxyribonucleic Acid Content Of Renal Oncocytomas: Flow Cytometric Analysis Of Paraffin-Embedded Tissues From Eight TumorsJournal of Urology, VOL. 136, NO. 2, (522-524), Online publication date: 1-Aug-1986.Ljungberg B, Stenling R and Roos G (2018) Prognostic Value of Deoxyribonucleic Acid Content in Metastatic Renal Cell CarcinomaJournal of Urology, VOL. 136, NO. 4, (801-804), Online publication date: 1-Oct-1986.deKernion J (2018) Renal Cell CarcinomaJournal of Urology, VOL. 136, NO. 4, (882-882), Online publication date: 1-Oct-1986.Psihramis K, Althausen A, Yoshida M, Prout G and Sandberg A (2018) Chromosome Anomalies Suggestive of Malignant Transformation in Bilateral Renal OncocytomaJournal of Urology, VOL. 136, NO. 4, (892-895), Online publication date: 1-Oct-1986.Ljungberg B, Forsslund G, Stenling R and Zetterberg A (2018) Prognostic Significance of the DNA Content in Renal Cell CarcinomaJournal of Urology, VOL. 135, NO. 2, (422-426), Online publication date: 1-Feb-1986.Rainwater L, Farrow G and Lieber M (2018) Flow Cytometry of Renal Oncocytoma: Common Occurrence of Deoxyribonucleic Acid Polyploidy and AneuploidyJournal of Urology, VOL. 135, NO. 6, (1167-1171), Online publication date: 1-Jun-1986.Chin J, Pontes J and Frankfurt O (2018) Flow Cytometric Deoxyribonucleic Acid Analysis of Primaryl and Metastatic Human Renal Cell CarcinomaJournal of Urology, VOL. 133, NO. 4, (582-585), Online publication date: 1-Apr-1985. Volume 132Issue 2August 1984Page: 237-239 Advertisement Copyright & Permissions© 1984 by The American Urological Association Education and Research, Inc.MetricsAuthor Information U. Otto More articles by this author H. Baisch More articles by this author H. Huland More articles by this author G. Klöppel More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract BACKGROUND. Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested. METHODS. In a cohort of 1132 men a nomogram was developed to predict the probability of IPCa. Predictors consisted of prostate‐specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length and percentage of positive biopsy cores (percent positive cores). IPCa was defined as organ‐confined PCa (OC) with tumor volume (TV) &lt;0.5 cc and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate IPCa nomogram was performed in the same group. RESULTS. IPCa was pathologically confirmed in 65 (5.7%) men. The 200 bootstrap‐corrected predictive accuracy of the new nomogram was 90% versus 81% for the older nomogram. However, in cutoff‐based analyses of patients who were qualified by our and the older nomograms as high probability for IPCa, respectively 63% and 45% harbored aggressive PCa variants at radical prostatectomy (Gleason score 7‐10, ECE, SVI, and/or LNI). CONCLUSIONS. Despite a high accuracy, currently available models for prediction of IPCa are incorrect in 10% to 20% of predictions. The rate of misclassification is even further inflated when specific cutoffs are used. As a consequence, extreme caution is advised when statistical tools are used to assign the diagnosis of IPCa. Cancer 2008. © 2008 American Cancer Society.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To examine the long‐term rates of biochemical recurrence (BCR)‐free survival, cancer‐specific mortality (CSM)‐free survival, and overall survival (OS) in patients with prostate cancer treated with open radical prostatectomy (RP) in the prostate‐specific antigen (PSA) era. PATIENTS AND METHODS The study comprised 436 patients who were treated with RP between 1992 and 1997 at our institution. None received adjuvant/salvage therapy in the absence of BCR. The BCR‐free, CSM‐free and OS rates were defined using the Kaplan‐Meier method. Multivariable Cox‐regression models were used to test the effect of age, preoperative PSA level, neoadjuvant hormonal therapy, pT stage, lymph node status, RP Gleason sum and surgical margin status on BCR. RESULTS The median follow‐up of censored patients was 122, 128, and 132 months for, respectively, BCR‐free, CSM‐free and OS estimates. The 10‐year event‐free survival rates for the same endpoints were 60%, 94% and 86%, respectively. Preoperative PSA level, RP Gleason sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (all adjusted P &lt; 0.05). CONCLUSIONS This study is the first to evaluate the long‐term cancer control outcomes after RP from a European country in the PSA era. Our data indicate that RP provides excellent long‐term survival rates in patients with clinically localized prostate cancer. Although ≈40% of patients have BCR after 10 years of follow‐up, the CSM rate after 10 years is as low as 6%.

A positive surgical margin after radical prostatectomy is considered an adverse prognostic feature. However, few groups have explored the potential interaction between surgical margin status and other cancer characteristics, specifically pathological stage. We addressed the first degree of interaction between positive surgical margins and other established adverse predictors of biochemical recurrence after radical prostatectomy.We used univariate and multivariate analysis to test the effect of surgical margin status on biochemical recurrence in 4,490 patients treated at a single institution between 1992 and 2008. We systematically tested all first-degree interactions between surgical margin status, and pretreatment prostate specific antigen, pT and pN stage, and radical prostatectomy Gleason sum. If interactions were significant, we quantified the effect on the biochemical recurrence rate.Overall 850 patients (18.9%) had positive surgical margins. In those with negative vs positive surgical margins the 5-year biochemical recurrence-free survival rate was 95% vs 83%, 74% vs 62% and 47% vs 29% for pT2, pT3a and pT3b disease, respectively. In multivariate models only the pT stage-surgical margin status interaction achieved independent predictor status (p = 0.003). Negative vs positive surgical margin multivariate HRs were 1 vs 2.9, 2.3 vs 4.3 and 4.1 vs 5.6 in pT2, pT3a and pT3b cases, respectively.Compared to negative surgical margins, positive surgical margins increase the absolute biochemical recurrence 5-year rate by 12% to 18%. More importantly, positive surgical margins may substantially worsen the prognosis beyond that of the original pathological disease stage.

To establish xenograft mouse models of metastatic and nonmetastatic human prostate cancer and to apply these models to the search for aberrant glycosylation patterns associated with tumor progression in vivo and in patients.Prostate cancer cells (LNCaP, PC-3, LuCaP 23.1, and DU-145) were xenografted subcutaneously into immunodeficient pfp(-/-)/rag2(-/-) mice. Tumor growth and metastasis formation were quantified and as altered glycosylation patterns have been associated with metastasis formation in several other malignancies, prostate cancer cells were profiled by a quantitative real-time PCR (qRT-PCR) glycosylation array and compared with normal human prostate cells. The activity of upregulated glycosyltransferases was analyzed by their sugar residues end products using lectin histochemistry on primary tumors and metastases in the animal experiments and on 2,085 clinical samples.PC-3 cells produced the largest number of spontaneous lung metastases, followed by LNCaP and LuCaP 23.1, whereas DU-145 was nonmetastatic. qRT-PCR revealed an upregulation of β1,6-N-acetylglucosaminyltransferase-5b (Mgat5b) in all prostate cancer cell lines. Mgat5b products [β(1,6)-branched oligosaccharides] were predominantly detectable in metastatic xenografts as shown by increased binding of Phaseolus vulgaris leukoagglutinin (PHA-L). The percentage of prostate cancer patients who were PHA-L positive was 86.5. PHA-L intensity correlated with serum prostate-specific antigen and a cytoplasmic staining negatively affected disease-free survival.We show a novel xenograft mouse model for human prostate cancer respecting the complete metastatic cascade. Specific glycosylation patterns reveal Mgat5b products as relevant markers of both metastatic competence in mice and disease-free survival in patients. This is the first description of Mgat5b in prostate cancer indicating a significant biologic importance of β(1,6)-branched oligosaccharides for prostate cancer progression.

The use of prostate-specific antigen (PSA) for screening or early detection of prostate cancer (PCa) results in significant stage migration toward more favorable stages and a proven decrease in PCa mortality but is accompanied by substantial rates of overdiagnosis and overtreatment. Acknowledgement of these downsides and endeavors to avoid them have led to substantial changes in treatment patterns. Many centers have reported dramatic changes, with increases in active surveillance (AS) of early cancers and local treatment of advanced disease. To estimate the impact of this development on our radical prostatectomy (RP) series, we analyzed changes in cancer and patient selection over the past 15 yr. Despite a trend toward decreased utilization of RP in Germany, the annual caseload at our institution increased due to regionalization, from 382 RPs in 2000 to 2145 in 2011, and has been stable for the past 3 yr (2106 RPs in 2014). The rate of RPs performed in patients with low-risk PCa, AS candidates, or men with a pure Gleason 6 pattern in the RP specimen dropped from 60%, 38.2%, and 56.2%, respectively, in 2004 to 27%, 14.7%, and 10%, respectively, in 2011–2013. Patients undergoing RP with solely Gleason 6 cancer were younger on average (aged 61 yr) than patients in higher risk groups (aged 65 yr). The rate of histologically insignificant PCa was low, ranging from 1% to 8.8% depending on the definition used. Patient selection is the other important tool used to avoid overtreatment. Long-term other-cause mortality (OCM) should be low in adequately selected RP candidates, and after a minimum follow-up of 15 yr, overall OCM was 14.8%. The OCM rate was 10.2% in men aged <65 yr and 24.3% in men aged ≥65 yr. The current analysis documents a clear shift in utilization of RP toward significant PCa in men with long life expectancy. Based on patient and cancer selection as described, the long-standing discussion of overtreatment with RP might become invalid. Discussion of possible overtreatment has led to dramatic changes in indication for radical prostatectomy (RP). We analyzed a large European patient cohort and found that RP is rarely done in early cancers but is used more for aggressive tumors. Those who underwent RP had long life expectancy and benefit from surgery. With this change in application, overtreatment with RP is unlikely.

The number of tumor-infiltrating lymphocytes is functionally important and correlates with clinical outcome in several tumor entities. Herein we explore the impact of the density of T and B lymphocytes in prostate cancer tissue on prostate-specific antigen (PSA) recurrence after prostatectomy in 3261 prostate cancer tissue samples. The number of prostate cancer-infiltrating CD3-positive T cells and CD20-positive B cells per tissue spot in a tissue microarray format was determined by immunohistochemistry and was correlated with clinical and pathological data from the same patient cohort. Patients with very low and very high numbers of CD3-positive T cells per tissue spot had a significantly shorter PSA recurrence-free survival compared to patients with intermediate numbers of T cells (p = 0.0188). Furthermore, a high number of CD3-positive T cells per tissue spot was associated with fusion type prostate cancer identified by ERG expression analysis. The number of CD20-positive B cells per tissue spot was not associated with other clinical and histopathological parameters. This study indicates that the density of T but not B cells plays a functional role in the biology of prostate cancer and may have an impact on clinical outcome in this frequent neoplasia.

As life expectancy increases, functional outcomes in elderly patients after radical prostatectomy (RP) become a more important factor to consider in treatment selection. The aim of this study was to determine age-dependant differences in functional outcomes after RP. A total of 8,295 patients who underwent RP from January 2009 to July 2013 were analyzed. Univariate and multivariate logistic regressions were used to estimate the effect of age and other covariates on 3- and 12-month continence and potency rates. Continence was achieved if no more than one safety pad was used per day. Potency was defined as an international index of erectile function (IIEF)-5 score of 18 or higher. In the entire cohort, 12-month (3-mo) continence and potency rates were 91.0% (76.1%) and 54.6% (40.9%), respectively. The 1-year continence rates for age groups<65,≥65 and<70,≥70 and<75, and≥75 years were 93.2%, 90.8%, 86.0%, and 86.5%, respectively. The corresponding 1-year potency rates were 59.3%, 46.9%, 44.4%, and 31.3%. In both, univariate and multivariate analyses, older age had a significant negative effect on functional outcomes. Moreover, nerve sparing, pT category, and patients’ body mass index were significantly associated with continence. Nerve sparing, pT category, patients’ body mass index, and use of PDE5 inhibitor or intracavernous injection therapy significantly influenced potency. Older age has a significant adverse effect on recovery of continence and potency. Although functional outcomes in elderly patients and especially in patients aged 75 years or older are still good, they should be educated about the increased risk of incontinence and impotence after RP.

While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy. To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP. Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT. Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score–matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP. Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (>3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received. Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment. Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.

Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete. To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice. Retrospective analysis of pathological and clinical data from 14 528 consecutive patients. Radical prostatectomy. The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint. Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p < 0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p < 0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p < 0.0001). Both N1 and L1 were linked to PSA recurrence (p < 0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1 mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients. Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence. Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.

To analyse time trends and contemporary rates of postoperative complications after radical prostatectomy (RP) and to compare the complication profile of open RP (ORP) and robot-assisted laparoscopic RP (RALP) using standardised reporting systems.Retrospective analysis of 13 924 RP patients in a single institution (2005-2015). Complications were collected during hospital stay and via standardised questionnaire 3 months after, and grouped into eight schemes. Since 2013, the revised Clavien-Dindo classification was used (n = 4 379). Annual incidence rates of different complications were graphically displayed. Multivariable logistic regression analyses compared complications between ORP and RALP after inverse probability of treatment weighting (IPTW).After the introduction of standardised classification systems, complication rates have increased with a contemporary rate of 20.6% (2013-2015). While minor Clavien-Dindo grades represented the majority (I: 10.6%; II: 7.9%), severe complications (Grades IV-V) were rare (<1%). In logistic regression analyses after IPTW, RALP was associated with less blood loss, shorter catheterisation time, and lower risk of Clavien-Dindo Grade II and III complications.Our results emphasise the importance of standardised reporting systems for quality control and comparison across approaches or institutions. Contemporary complication rates in a high-volume centre remain low and are most frequently minor Clavien-Dindo grades. RALP had a slightly better complication profile compared to ORP.

Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P<.0001 each). Comparison with our molecular database attached to the TMA revealed that BGN expression was linked to presence of TMPRRS2:ERG fusion and PTEN deletion (P<.0001 each). In addition, BGN was strongly linked to androgen-receptor (AR) levels (P<.0001), suggesting a hormone-depending regulation of BGN. BGN up-regulation is a frequent feature of prostate cancer that parallels tumor progression and may be useful to estimate tumor aggressiveness particularly if combined with other molecular markers.

Neurovascular bundle (NVB) preservation (NVBP) and surgical margin status are the main intraoperative factors influencing functional and oncologic outcomes in patients with prostate cancer undergoing radical prostatectomy (RP).To test the impact of implementing the intraoperative frozen section technique (IFST) during NVBP on the frequency of NVB procedures and its effect on positive surgical margins (PSMs).We relied on an institutional tertiary-care center database to identify patients who underwent RP (January 2014-October 2018). Until October 2017, decision for NVBP was taken based on preoperative magnetic resonance imaging, clinical characteristics, and nomograms, without the IFST. After November 2017, all patients received bilateral NVBP with the IFST, to check for a PSM in the area of the NVB. If a PSM occurred, a secondary resection of the respective NVB was performed.PSM and NVB procedures were assessed. Subgroup analyses focused on pathologic tumor stages.Overall, 346 patients were identified. Of these patients, 54.9% (n=190) versus 45.1% (n=156) underwent RP without versus with the IFST. By using the IFST during NVBP, the PSM decreased from 29.5% to 15.4% (p=0.003) in the entire cohort (14.6% vs 8.6% in pT2; 47.1% vs 29.4% in pT3). Conversely, NVBP increased from 55.3% to 95.5% (p<0.001) in the entire cohort (68.9% vs 99.0% in pT2; 39.1% vs 88.2% in pT3). In multivariable logistic regressions, IFST use was an independent predictor of PSMs (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.30-0.98; p=0.047) and NVBP (OR: 5.60, 95% CI: 3.10-10.51; p<0.001) after controlling for patient and tumor characteristics.Implementation of the IFST during NVBP resulted in more frequent NVBP and was associated with a lower PSM, compared with RP without the IFST. Therefore, the IFST should be performed, if available.The intraoperative frozen section technique (IFST) during preservation of neurovascular bundles (NVBP) should be offered to patients who undergo radical prostatectomy. The IFST can reduce positive margin rates and increase the rate of NVBP.

The prognostic value of circulating tumor cells (CTCs) in patients with hormone-naïve oligometastatic prostate cancer (HNoMPC) undergoing cytoreductive radical prostatectomy (CRP) is unknown.To determine the pre- and postoperative prognostic value of CTC enumeration in patients undergoing CRP.Thirty-three patients with HNoMPC from the prospective, single-arm ProMPT trial who underwent CRP between 2014 and 2015 at the Martini-Klinik were evaluated. Follow-up visits for all patients were conducted every 6 mo up to 36 mo after CRP and included serial detection of CTCs in 7.5 ml blood samples using the CellSearch system.CRP.CTC enumerations before and after CRP, and their prognostic value on metastatic castration-resistant prostate cancer-free survival and overall survival (OS) were analyzed using Kaplan-Meier plots and univariable Cox-regression analysis.Sixteen patients (48.5%) had positive CTCs prior to CRP. A CTC count of ≥2 before or 6 mo after CRP was a prognostic factor for worse oncologic outcome. Compared with other biomarkers (prostate-specific antigen, lactate dehydrogenase, and bone-specific alkaline phosphatase), the prognostic value of CTCs was highest using Harrell's C for OS (0.69), while the highest C-index could be achieved for a combination of conventional markers and CTC count (0.74). After progression to metastatic castration-resistant prostate cancer, CTC enumeration of ≥5 was prognostic for OS. The main limitation is the small sample size.CTC enumeration contributes to prognostic information, which might help select HNoMPC patients who might benefit most from CRP.In this report, we looked at the value of circulating tumor cell (CTC) determination in patients undergoing radical prostatectomy for oligometastatic prostate cancer. We could show that the number of CTCs was a prognostic factor at all analyzed time points and was more closely associated with prognosis than other biomarkers commonly used in daily clinical practice.

This study was undertaken to distinguish between patients who will and will not benefit from a retropubic radical prostatectomy (RRP) for clinically localized prostatic carcinoma (PCa) on the basis of preoperative and postoperative tumor characteristics.Data of 318 consecutive patients who underwent RRP for clinically localized PCa were reviewed. Preoperative characteristics used included clinical stage, findings on transrectal ultrasonography, prostate-specific antigen (PSA) values, Gleason grade, number of positive biopsies, number of biopsies containing any Gleason grade 4 and/or 5 cancer, and number of biopsies with predominant (>50% of cancerous tissue) Gleason grade 4 and/or 5 cancer. Postoperative characteristics included pathologic stage, Gleason grade, margin status, cancer volume, and volume of Gleason grade 4 and/or 5 cancer. The impact on biochemical relapse after RRP were calculated by Cox regression and CART (classification and regression tree) analysis to establish low, intermediate, and high risk of recurrence.Of patients who underwent RRP, 66% showed no evidence of relapse after a follow-up of 42 months. All preoperative and postoperative characteristics showed a significant association with biochemical relapse. Cox regression of preoperative characteristics showed the number of positive biopsies with predominant Gleason grade 4 and/or 5 cancer to be the most accurate predictor of failure (p < 0.0001), followed by the number of positive biopsies and PSA. CART analysis distinguished between four risk groups on the basis of the same characteristics as in the Cox regression. The low-risk group consisted of 232 patients (75.1%) and the high-risk group of 17 patients (5.5%); corresponding Kaplan-Meier curves showed a 2-year PSA-free survival rate of 97% for the low-risk group and 20% for the high-risk group. Cox regression of postoperative characteristics recognized the volume of Gleason grade 4 and/or 5 as the characteristic with the strongest association with biochemical failure. CART analysis distinguished between four risk groups, using the volume of high-grade cancer as the most influential characteristic. The corresponding Kaplan-Meier curves showed for the low-risk group (n = 79; 29.6%) a PSA-free survival rate of 96% after 42 months and for the high-risk group (n = 47; 17.6%) a 21% PSA-free survival rate after 42 months.For preoperative and postoperative estimation of biochemical recurrence after RRP, a quantitative analysis of high-grade cancer, expressed by the number of preoperative biopsy cores containing high-grade cancer and the volume of cancer, proved to be the best predictor of relapse. CART analysis might be useful in advising patients for their best therapy options. However, defined characteristics of risk groups should be evaluated with new prospective data before they are used routinely.

Objectives: Transition zone (TZ) carcinomas of the prostate are thought to have less malignant potential than tumours that arise in the peripheral zone (PZ). It is unclear, however, whether this can be put down to anatomical reasons alone, or if there are further differences between tumours of both zones. Methods: We examined Gleason scores, proliferation and apoptosis rates, microvessel density (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic cells. Proliferation, MVD, p53, and bcl-2 were investigated by immunohistochemistry. Results: There were significant differences between TZ tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P<0.0001), the proliferation rate (3.2% versus 5.2%; P=0.0003), and the MVD (68.5 versus 104; P=0.0002), but the median apoptosis rate was quite similar (0.8% versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively). Conclusion: There is evidence for lower Gleason scores as well as lower expression of markers related to tumour growth in TZ carcinomas of the prostate, which might contribute to a less malignant clinical behaviour as compared to PZ cancers.

Objectives: To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer.Methods: 1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes.Results: Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm3) remained stable between 2 and 5% over the last 5 years.Conclusion: The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.

Here, we show that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in umbrella cells of bladder urothelium but is down-regulated in superficial bladder cancer, such as histologic tumor stage a (pTa) and transitional cell carcinoma in situ (pTis). Concurrently, CEACAM1 is up-regulated in the endothelia of adjacent angiogenic blood vessels. Mimicking the CEACAM1 down-regulation in the urothelium, CEACAM1 was silenced in bladder cancer cell lines 486p and RT4 using the small interfering RNA technique. CEACAM1 down-regulation was confirmed at the protein level by Western blot analyses. CEACAM1 silencing leads to a significant up-regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D in quantitative reverse transcription-PCR. Correspondingly, supernatants from the CEACAM1-overexpressing bladder cancer cell lines reduce, but those from CEACAM1 silencing induce endothelial tube formation and potentiate the morphogenetic effects of VEGF. These data suggest that the epithelial down-regulation of CEACAM1 induces angiogenesis via increased expression of VEGF-C and VEGF-D. Inversely, CEACAM1 is up-regulated in endothelial cells of angiogenic blood vessels. This in turn is involved in the switch from noninvasive and nonvascularized to invasive and vascularized bladder cancer. CEACAM1 appears to be a promising endothelial target for bladder cancer therapy.

No AccessJournal of UrologyAdult urology1 Sep 2006Variability in the Performance of Nuclear Matrix Protein 22 for the Detection of Bladder Cancer Shahrokh F. Shariat, Michael J. Marberger, Yair Lotan, Marta Sanchez-Carbayo, Craig Zippe, Gerson Lüdecke, Hans Boman, Ihor Sawczuk, Martin G. Friedrich, Roberto Casella, Christine Mian, Sanaa Eissa, Hideyuki Akaza, Vincenzo Serretta, Hartwig Huland, Hans Hedelin, Rupesh Raina, Naoto Miyanaga, Arthur I. Sagalowsky, Claus G. Roehrborn, and Pierre I. Karakiewicz Shahrokh F. ShariatShahrokh F. Shariat Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , Michael J. MarbergerMichael J. Marberger Department of Urology, University of Vienna, Vienna, Austria More articles by this author , Yair LotanYair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , Marta Sanchez-CarbayoMarta Sanchez-Carbayo Servicio de Bioquimica, Hospital Universitario de Salamanca, Salamanca, Spain More articles by this author , Craig ZippeCraig Zippe Cleveland Clinic Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Gerson LüdeckeGerson Lüdecke Departments of Urology, Justus-Liebig University, Giessen, Germany More articles by this author , Hans BomanHans Boman Department of Urology, Kärnsjukhuset Skövde, Skövde, Sweden More articles by this author , Ihor SawczukIhor Sawczuk Hackensack University Medical Center/College of Physicians and Surgeons, Columbia University, New York, New York More articles by this author , Martin G. FriedrichMartin G. Friedrich University of Hamburg, Hamburg, Germany More articles by this author , Roberto CasellaRoberto Casella Hospital Center Biel, Biel, Switzerland More articles by this author , Christine MianChristine Mian Department of Pathology, Bolzano, Italy More articles by this author , Sanaa EissaSanaa Eissa Oncology Diagnostic Unit, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt More articles by this author , Hideyuki AkazaHideyuki Akaza Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan More articles by this author , Vincenzo SerrettaVincenzo Serretta Institute of Urology, University of Palermo, Italy More articles by this author , Hartwig HulandHartwig Huland University of Hamburg, Hamburg, Germany More articles by this author , Hans HedelinHans Hedelin Department of Urology, Kärnsjukhuset Skövde, Skövde, Sweden More articles by this author , Rupesh RainaRupesh Raina Cleveland Clinic Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Naoto MiyanagaNaoto Miyanaga Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan More articles by this author , Arthur I. SagalowskyArthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , Claus G. RoehrbornClaus G. Roehrborn Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz Department of Urology, University of Montreal, Montreal, Quebec, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2006.04.017AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We assessed variability in the diagnostic performance of NMP22® for detecting recurrence and progression in patients with Ta, T1, and/or CIS transitional cell carcinoma of the bladder in a large international cohort. Materials and Methods: NMP22® voided urine levels were measured in 2,871 patients who underwent office cystoscopy for monitoring previous stage Ta, T1 and/or CIS transitional cell carcinoma at 12 participating institutions. Results: Patient characteristics varied considerably among institutions. Overall 1,045 patients (36.4%) had recurrent transitional cell carcinoma (range across institutions 13.6% to 54.3%). Median NMP22® was 5.5 U/ml (range across institutions 2.5 to 18.8). Of the patients 33.5% had grade III tumors (range across institutions 20.6% to 54.0%) and 22.4% had muscle invasive tumors (range across institutions 3.2% to 38.2%). Area under the ROC curve for bladder TCC detection was 0.735 (95% CI 0.715 to 0.755, range across institutions 0.676 to 0.889). The manufacturer recommended cutoff of 10 U/ml detected 57% of cases with a 19% false-positive rate. AUC for grade III and stage T2 or greater disease was 0.806 (95% CI 0.780 to 831) and 0.864 (95% CI 0.839 to 0.890), respectively. For each NMP22® cutoff NMP22® had higher sensitivity for detecting grade III and stage T2 or greater bladder transitional cell carcinoma than for detecting any cancer. No optimal cutoffs for detecting any or aggressive bladder transitional cell carcinoma could be derived based on NMP22® values. Conclusions: There is a substantial degree of heterogeneity in the diagnostic performance of NMP22® applied to populations from different institutions. There is no clearly defined NMP22® cutoff but there is a continuum of risk for recurrence and progression. References 1 : Use of new tumor marker, urinary NMP22, in detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol1996; 156: 363. Link, Google Scholar 2 : Risk stratification for bladder tumor recurrence, stage and grade by urinary nuclear matrix protein 22 and cytology. Eur Urol2004; 45: 304. Google Scholar 3 : The addition of urinary urokinase-type plasminogen activator to urinary nuclear matrix protein 22 and cytology improves the detection of bladder cancer. J Urol2003; 170: 2244. Link, Google Scholar 4 : Urine detection of survivin is a sensitive marker for the noninvasive diagnosis of bladder cancer. J Urol2004; 171: 626. Link, Google Scholar 5 : Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat. J Urol1999; 162: 53. Link, Google Scholar 6 : Evaluation of NMP22 as a tumor marker in the detection of transitional cell carcinoma of the bladder. BJU Int1999; 84: 706. Google Scholar 7 : Comparative predictive values of urinary cytology, urinary bladder cancer antigen, CYFRA 21-1 and NMP22 for evaluating symptomatic patients at risk for bladder cancer. J Urol2001; 165: 1462. Link, Google Scholar 8 : Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria. Int J Urol1999; 6: 173. Google Scholar 9 : Urinary NMP22 for the detection of recurrence after transurethral resection of transitional cell carcinoma of the bladder: experience on 137 patients. Urology1998; 52: 793. Crossref, Medline, Google Scholar 10 : Evaluation of NMP22 in the detection of transitional cell carcinoma of the bladder. J Urol1998; 159: 394. Link, Google Scholar 11 : Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor. J Urol2000; 164: 1926. Link, Google Scholar 12 : Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder. J Urol2005; 173: 1518. Link, Google Scholar 13 : Are false-positive urine markers for the detection of bladder carcinoma really wrong or do they predict tumor recurrence?. Eur Urol2003; 43: 146. Google Scholar 14 : Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection. Int J Clin Oncol2003; 8: 369. Google Scholar 15 : Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence. J Urol2002; 167: 80. Link, Google Scholar 16 : Screening and monitoring for bladder cancer: refining the use of NMP22. J Urol2001; 166: 75. Link, Google Scholar 17 : Cost-effectiveness of a modified care protocol substituting bladder tumor markers for cystoscopy for the followup of patients with transitional cell carcinoma of the bladder: a decision analytical approach. J Urol2002; 167: 75. Link, Google Scholar © 2006 by American Urological AssociationFiguresReferencesRelatedDetailsCited byTodenhöfer T, Hennenlotter J, Witstruk M, Gakis G, Aufderklamm S, Kuehs U, Stenzl A and Schwentner C (2018) Influence of Renal Excretory Function on the Performance of Urine Based Markers to Detect Bladder CancerJournal of Urology, VOL. 187, NO. 1, (68-73), Online publication date: 1-Jan-2012. Volume 176 Issue 3 September 2006 Page: 919-926 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordsbladderbladder neoplasmsnuclear matrix protein 22tumor markersbiologicalMetrics Author Information Shahrokh F. Shariat Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Michael J. Marberger Department of Urology, University of Vienna, Vienna, Austria More articles by this author Yair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Marta Sanchez-Carbayo Servicio de Bioquimica, Hospital Universitario de Salamanca, Salamanca, Spain More articles by this author Craig Zippe Cleveland Clinic Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Gerson Lüdecke Departments of Urology, Justus-Liebig University, Giessen, Germany More articles by this author Hans Boman Department of Urology, Kärnsjukhuset Skövde, Skövde, Sweden More articles by this author Ihor Sawczuk Hackensack University Medical Center/College of Physicians and Surgeons, Columbia University, New York, New York More articles by this author Martin G. Friedrich University of Hamburg, Hamburg, Germany More articles by this author Roberto Casella Hospital Center Biel, Biel, Switzerland More articles by this author Christine Mian Department of Pathology, Bolzano, Italy More articles by this author Sanaa Eissa Oncology Diagnostic Unit, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt More articles by this author Hideyuki Akaza Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan More articles by this author Vincenzo Serretta Institute of Urology, University of Palermo, Italy More articles by this author Hartwig Huland University of Hamburg, Hamburg, Germany More articles by this author Hans Hedelin Department of Urology, Kärnsjukhuset Skövde, Skövde, Sweden More articles by this author Rupesh Raina Cleveland Clinic Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Naoto Miyanaga Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan More articles by this author Arthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Claus G. Roehrborn Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Pierre I. Karakiewicz Department of Urology, University of Montreal, Montreal, Quebec, Canada More articles by this author Expand All Advertisement PDF downloadLoading ...

Several nomograms have been developed to predict outcomes related to prostate cancer (PCa).We provide a descriptive and an analytic comparison of nomograms. Further, we report a set of recent PCa nomograms, in which we recorded predictor variables, number of patients used to develop each nomogram, and nomogram-specific features. Moreover, accuracy estimates and type of validation are considered.Our findings suggest a demand for updated nomograms in selected fields of PCa outcomes. Moreover, an increasing number of nomograms address important end points such as prostate-specific antigen recurrence, distant metastases, or androgen-independent PCa-specific survival.Our results suggest that nomograms are available for many PCa-related outcomes. They represent a valid methodologic approach if correct criteria are met.

Objectives: The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test. Methods: A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated. Results: The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively. Conclusions: The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.

Background. Experimental studies suggest that the infiltration of activated T cells into the allograft, the key event in the development of acute renal allograft rejection, depends on the expression of chemokines and their interaction with chemokine receptors expressed on T cells. Methods. For a more detailed comprehension of the pathogenesis of T-cell recruitment in human acute rejection, the in situ expression of chemokines and chemokine receptors in allografts of 26 patients between day 3 and 9 after renal transplantation was examined in the present prospective study. Results. Immunohistochemical staining showed a significantly increased number of CXCR3 (P<0.01) and CCR5 positive T cells (P<0.01) in the tubulointerstitium of patients with acute allograft rejection according to Banff grade Ia-IIb. Likewise the intrarenal RNA expression of the CXCR3 ligands IP-10 (5.2-fold) and I-TAC (7.2-fold) and the CCR5 ligand RANTES (5.7-fold), was significantly up-regulated in rejecting organs. In situ hybridization revealed that IP-10 but not I-TAC was predominantly expressed by infiltrating leukocytes in the tubulointerstitial area, co-localizing with CXCR3 positive T cells. To a lesser degree expression by tubular cells could be detected, providing a possible explanation for the increased urinary IP-10 excretion we found in patients with rejecting organs. Conclusions. These data from a prospective, biopsy-controlled study indicate that the local expression of IP-10 and RANTES leads to the directional movement of activated CXCR3 and CCR5 bearing T cells into the renal allograft and mediates acute rejection. Our data provide a rationale that blocking CXCR3 and CCR5 may offer a unique therapeutic approach to prevent episodes of acute rejection in the early phase after renal transplantation.