Markus Graefen

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

Despite the wide diffusion of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP), only few studies comparing the results of these techniques with the retropubic radical prostatectomy (RRP) are currently available.To evaluate the perioperative, functional, and oncologic results in the comparative studies evaluating RRP, LRP, and RALP.A systematic review of the literature was performed in January 2008, searching Medline, Embase, and Web of Science databases. A "free-text" protocol using the term radical prostatectomy was applied. Some 4000 records were retrieved from the Medline database; 2265 records were retrieved from the Embase database;, and 4219 records were retrieved from the Web of Science database. Three of the authors reviewed the records to identify comparative studies. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK).Thirty-seven comparative studies were identified in the literature search, including a single, randomised, controlled trial. With regard to the perioperative outcome, LRP and RALP were more time consuming than RRP, especially in the initial steps of the learning curve, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates all favoured LRP. With regard to the functional results, LRP and RRP showed similar continence and potency rates. Similarly, no significant differences were identified between LRP and RALP, while a single, nonrandomised, prospective study suggested advantages in terms of both continence and potency recovery after RALP, compared with RRP. With regard to the oncologic outcome, LRP and RALP were associated with positive surgical margin rates similar to those of RRP.The quality of the available comparative studies was not excellent. LRP and RALP are followed by significantly lower blood loss and transfusion rates, but the available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. Further high-quality, prospective, multicentre, comparative studies are needed.

Although the initial robot-assisted radical prostatectomy (RARP) series showed 12-mo potency rates ranging from 70% to 80%, the few available comparative studies did not permit any definitive conclusion about the superiority of this technique when compared with retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP).The aims of this systematic review were (1) to evaluate the current prevalence and the potential risk factors of erectile dysfunction after RARP, (2) to identify surgical techniques able to improve the rate of potency recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP.A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. Only comparative studies or clinical series including >100 cases reporting potency recovery outcomes were included in this review. Cumulative analysis was conducted using Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK).We analyzed 15 case series, 6 studies comparing different techniques in the context of RARP, 6 studies comparing RARP with RRP, and 4 studies comparing RARP with LRP. The 12- and 24-mo potency rates ranged from 54% to 90% and from 63% to 94%, respectively. Age, baseline potency status, comorbidities index, and extension of the nerve-sparing procedure represent the most relevant preoperative and intraoperative predictors of potency recovery after RARP. Available data seem to support the use of cautery-free dissection or the use of pinpointed low-energy cauterization. Cumulative analyses showed better 12-mo potency rates after RARP in comparison with RRP (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 1.46-5.43; p=0.002). Only a nonstatistically significant trend in favor of RARP was reported after comparison with LRP (OR: 1.89; p=0.21).The incidence of potency recovery after RARP is influenced by numerous factors. Data coming from the present systematic review support the use of a cautery-free technique. This update of previous systematic reviews of the literature showed, for the first time, a significant advantage in favor of RARP in comparison with RRP in terms of 12-mo potency rates.

BackgroundWe assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases.Patients and methodsPatients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998–2007). Age was stratified into four groups: <55, 55–64, 65–74 and ≥75 years. Cochran–Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites.ResultsIn 11 157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases.ConclusionsThe proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%–49%) and brain (2%–16%) metastases are nonnegligible in mRCC patients.

The incidence of postoperative complications is still the most frequently used surrogate marker of quality in surgery, but no standard guidelines or criteria exist for reporting surgical complications in the area of urology.To review the available reporting systems used for urologic surgical complications, to establish a possible change in attitude towards reporting of complications using standardised systems, to assess systematically the Clavien-Dindo system when used for the reporting of complications related to urologic surgical procedures, to identify shortcomings in reporting complications, and to propose recommendations for the development and implementation of future reporting systems that are focused on patient-centred outcomes.Standardised systems for reporting and classification of surgical complications were identified through a systematic review of the literature. To establish a possible change in attitude towards reporting of complications related to urologic procedures, we performed a systematic literature search of all papers reporting complications after urologic surgery published in European Urology, Journal of Urology, Urology, BJU International, and World Journal of Urology in 1999-2000 and 2009-2010. Data identification for the systematic assessment of the Clavien-Dindo system currently used for the reporting of complications related to urologic surgical interventions involved a Medline/Embase search and the search engines of individual urologic journals and publishers using Clavien, urology, and complications as keywords. All selected papers were full-text retrieved and assessed; analysis was done based on structured forms.The systematic review of the literature for standardised systems used for reporting and classification of surgical complications revealed five such systems. As far as the attitude of urologists towards reporting of complications, a shift could be seen in the number of studies using most of the Martin criteria, as well as in the number of studies using either standardised criteria or the Clavien-Dindo system. The latter system was not properly used in 72 papers (35.3%).Uniformed reporting of complications after urologic procedures will aid all those involved in patient care and scientific publishing (authors, reviewers, and editors). It will also contribute to the improvement of the scientific quality of papers published in the field of urologic surgery. When reporting the outcomes of urologic procedures, the committee proposes a series of quality criteria.

Pelvic lymph node dissection (PLND) is considered the most reliable procedure for the detection of lymph node metastases in prostate cancer (PCa); however, the therapeutic benefit of PLND in PCa management is currently under debate. To systematically review the available literature concerning the role of PLND and its extent in PCa staging and outcome. All of the existing recommendations and staging tools determining the need for PLND were also assessed. Moreover, a systematic review was performed of the long-term outcome of node-positive patients stratified according to the extent of nodal invasion. A Medline search was conducted to identify original and review articles as well as editorials addressing the significance of PLND in PCa. Keywords included prostate cancer, pelvic lymph node dissection, radical prostatectomy, imaging, and complications. Data from the selected studies focussing on the role of PLND in PCa staging and outcome were reviewed and discussed by all of the contributing authors. Despite recent advances in imaging techniques, PLND remains the most accurate staging procedure for the detection of lymph node invasion (LNI) in PCa. The rate of LNI increases with the extent of PLND. Extended PLND (ePLND; ie, removal of obturator, external iliac, hypogastric with or without presacral and common iliac nodes) significantly improves the detection of lymph node metastases compared with limited PLND (lPLND; ie, removal of obturator with or without external iliac nodes), which is associated with poor staging accuracy. Because not all patients with PCa are at the same risk of harbouring nodal metastases, several nomograms and tables have been developed and validated to identify candidates for PLND. These tools, however, are based mostly on findings derived from lPLND dissections performed in older patient series. According to these prediction models, a staging PLND might be omitted in low-risk PCa patients because of the low rate of lymph node metastases found, even after extended dissections (<8%). The outcome for patients with positive nodes is not necessarily poor. Indeed, patients with low-volume nodal metastases experience excellent survival rates, regardless of adjuvant treatment. But despite few retrospective studies reporting an association between PLND and PCa progression and survival, the exact impact of PLND on patient outcomes has not yet been clearly proven because of the lack of prospective randomised trials. On the basis of current data, we suggest that if a PLND is indicated, then it should be extended. Conversely, in view of the low rate of LNI among patients with low-risk PCa, a staging ePLND might be spared in this patient category. Whether this approach is also safe from oncologic perspectives is still unknown. Patients with low-volume nodal metastases have a good long-term prognosis; to what extent this prognosis is the result of a positive impact of PLND on PCa outcomes is still to be determined.

Despite the large diffusion of robot-assisted radical prostatectomy (RARP), literature and data on the oncologic outcome of RARP are limited. Evaluate lymph node yield, positive surgical margins (PSMs), use of adjuvant therapy, and biochemical recurrence (BCR)–free survival following RARP and perform a cumulative analysis of all studies comparing the oncologic outcomes of RARP and retropubic radical prostatectomy (RRP) or laparoscopic radical prostatectomy (LRP). A systematic review of the literature was performed in August 2011, searching Medline, Embase, and Web of Science databases. A free-text protocol using the term radical prostatectomy was applied. The following limits were used: humans; gender (male); and publications dating from January 1, 2008. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK) and Stata 11.0 SE software (StataCorp, College Station, TX, USA). We retrieved 79 papers evaluating oncologic outcomes following RARP. The mean PSM rate was 15% in all comers and 9% in pathologically localized cancers, with some tumor characteristics being the most relevant predictors of PSMs. Several surgeon-related characteristics or procedure-related issues may play a major role in PSM rates. With regard to BCR, the very few papers with a follow-up duration >5 yr demonstrated 7-yr BCR-free survival estimates of approximately 80%. Finally, all the cumulative analyses comparing RARP with RRP and comparing RARP with LRP demonstrated similar overall PSM rates (RARP vs RRP: odds ratio [OR]: 1.21; p = 0.19; RARP vs LRP: OR: 1.12; p = 0.47), pT2 PSM rates (RARP vs RRP: OR: 1.25; p = 0.31; RARP vs LRP: OR: 0.99; p = 0.97), and BCR-free survival estimates (RARP vs RRP: hazard ratio [HR]: 0.9; p = 0.526; RARP vs LRP: HR: 0.5; p = 0.141), regardless of the surgical approach. PSM rates are similar following RARP, RRP, and LRP. The few data available on BCR from high-volume centers are promising, but definitive comparisons with RRP or LRP are not currently possible. Finally, significant data on cancer-specific mortality are not currently available.

Perioperative complications are a major surgical outcome for radical prostatectomy (RP).Evaluate complication rates following robot-assisted RP (RARP), risk factors for complications after RARP, and surgical techniques to improve complication rates after RARP. We also performed a cumulative analysis of all studies comparing RARP with retropubic RP (RRP) or laparoscopic RP (LRP) in terms of perioperative complications.A systematic review of the literature was performed in August 2011, searching Medline, Embase, and Web of Science databases. A free-text protocol using the term radical prostatectomy was applied. The following limits were used: humans; gender (male); and publications dating from January 1, 2008. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK).We retrieved 110 papers evaluating oncologic outcomes following RARP. Overall mean operative time is 152 min; mean blood loss is 166 ml; mean transfusion rate is 2%; mean catheterization time is 6.3 d; and mean in-hospital stay is 1.9 d. The mean complication rate was 9%, with most of the complications being of low grade. Lymphocele/lymphorrea (3.1%), urine leak (1.8%), and reoperation (1.6%) are the most prevalent surgical complications. Blood loss (weighted mean difference: 582.77; p<0.00001) and transfusion rate (odds ratio [OR]: 7.55; p<0.00001) were lower in RARP than in RRP, whereas only transfusion rate (OR: 2.56; p=0.005) was lower in RARP than in LRP. All the other analyzed parameters were similar, regardless of the surgical approach.RARP can be performed routinely with a relatively small risk of complications. Surgical experience, clinical patient characteristics, and cancer characteristics may affect the risk of complications. Cumulative analyses demonstrated that blood loss and transfusion rates were significantly lower with RARP than with RRP, and transfusion rates were lower with RARP than with LRP, although all other features were similar regardless of the surgical approach.

Detailed knowledge of the anatomy of the prostate and adjacent tissues is mandatory during radical prostatectomy to ensure reliable oncologic and functional outcomes. To review critically and to summarize the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control, erectile function, and urinary continence. A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis, and sphincter. Relevant articles and textbook chapters were reviewed, analyzed, and summarized. Anatomy of the prostate and the adjacent tissues varies substantially. The fascia surrounding the prostate is multilayered, sometimes either fused with the prostate capsule or clearly separated from the capsule as a reflection of interindividual variations. The neurovascular bundle (NVB) is situated between the fascial layers covering the prostate. The NVB is composed of numerous nerve fibers superimposed on a scaffold of veins, arteries, and variable amounts of adipose tissue surrounding almost the entire lateral and posterior surfaces of the prostate. The NVB is also in close, cage-like contact to the seminal vesicles. The external urethral sphincter is a complex structure in close anatomic and functional relationship to the pelvic floor, and its fragile innervation is in close association to the prostate apex. Finally, the shape and size of the prostate can significantly modify the anatomy of the NVB, the urethral sphincter, the dorsal vascular complex, and the pubovesical/puboprostatic ligaments. The surgical anatomy of the prostate and adjacent tissues involved in radical prostatectomy is complex. Precise knowledge of all relevant anatomic structures facilitates surgical orientation and dissection during radical prostatectomy and ideally translates into both superior rates of cancer control and improved functional outcomes postoperatively.

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.

The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear.To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management.A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP.A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5-32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer-specific mortality, and overall survival remains debatable.Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative.

To date, no data have been available from large, well-designed trials comparing on demand and nightly dosing of phosphodiesterase type 5 (PDE5) inhibitors on recovery of erectile function in postprostatectomy patients with erectile dysfunction (ED). To investigate the effect of early postoperative dosing with vardenafil, administered either nightly or on demand, compared with placebo on recovery of erectile function in men with ED following bilateral nerve-sparing radical prostatectomy (NSRP) surgery. A randomised, double-blind, double-dummy, multicentre, parallel group study conducted at 87 centres across Europe, Canada, South Africa, and the United States. For inclusion, patients had to be scheduled to undergo bilateral NSRP within 1 mo of screening and have a normal International Index of Erectile Function erectile function domain (IIEF-EF) score of ≥26 at screening. A total of 628 men, aged 18–64 yr, were randomised to treatment. Study design consisted of a 9-mo double-blind treatment period, a 2-mo single-blind washout period, and an optional 2-mo open-label period. Patients received placebo, nightly vardenafil, or on demand vardenafil. Primary outcome measure was the percentage of subjects with an IIEF-EF score of ≥22 after the 2-mo washout period. Secondary variables included mean per-patient success rates for Sexual Encounter Profile (SEP) questions 2 and 3. No statistically significant differences were observed among treatment groups in the proportion of patients with an IIEF-EF score of ≥22 or in SEP3 success rates after the washout period. On-demand vardenafil treatment resulted in significantly greater IIEF-EF scores and better SEP3 response rates than placebo over the entire treatment period. In this study of men with ED following bilateral NSRP, vardenafil was efficacious when used on demand, supporting a paradigm shift towards on demand dosing with PDE5 inhibitors in this patient group. European clinical trials database (EudraCT; available at http://eudract.emea.europa.eu/). Trial registration number: 11336.

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naïve and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P < 0.0001), presence of ERG gene fusion (P < 0.0001), and nuclear p53 accumulation (P < 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P < 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers.

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.

Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option. We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies. A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Positive surgical margins in SRP varied from 43% to 70% in earlier publications versus 0–36% in recent publications, and pathologic organ-confined disease (OCD) was found in 22–53% versus 44–73% in earlier versus recent publications. Biochemical recurrence–free probability after SRP ranged from 47% to 82% at 5 yr and from 28% to 53% at 10 yr. Cancer-specific survival (CSS) and overall survival varied from 70% to 83% and 54% to 89% at 10 yr. Pre-SRP prostate-specific antigen value and prostate biopsy Gleason score were the strongest prognostic risk factors for progression-free survival, OCD, and CSS. Open, laparoscopic, and robotic techniques were shown to be feasible in the hands of experienced surgeons. The most frequent complications included anastomotic stricture (7–41%) followed by rectal injury (0–28%). Major complications (modified Clavien classification grade 3–5) varied from 0% to 25%. Most complications were less frequent in more recent series, except for anastomotic stricture. The majority of patients had erectile dysfunction prior to SRP (50–91%) and 80–100% after SRP. Urinary continence ranged from 21% to 90% after surgery. Limitations of this review include the absence of prospective studies and lack of comparative analyses between SRP and other therapies. In selected patients with confirmed, localized, radiation-recurrent PCa, SRP may effectively promote durable cancer control with acceptable associated surgical morbidity and variable functional recovery.

Abstract Purpose: About 50% of prostate cancers have TMPRSS2–ERG fusions with concurrent ERG overexpression. The aim of this study was to determine whether clinical differences exist between ERG-positive and ERG-negative cancers in surgically treated patients not exposed to antihormonal therapy. A secondary aim was to search for differences between these tumor classes. Experimental Design: A tissue microarray containing samples from more than 2,800 prostate cancers with clinical data was analyzed for ERG alterations by immunohistochemistry and FISH. Results were compared with tumor phenotype, biochemical recurrence, and molecular features considered important for prostate cancer. The effect of ERG on androgen receptor (AR)-dependent transcription was analyzed in cell lines. Results: ERG expression was found in 52.4% of 2,805 cancers with a 95% concordance between ERG expression and ERG gene rearrangement detected by FISH. ERG expression was unrelated to clinical outcome and tumor phenotype. Differences in AMACR, Annexin A3, Bcl2, CD10, ALCAM, chromogranin A, epidermal growth factor receptor, HER2, mTOR, p53, and synaptophysin status were significant but minimal in absolute numbers. The most striking difference was found for AR expression, which was markedly higher in ERG-positive cancers. In vitro studies showed ERG-dependent impairment of AR-mediated transcriptional activity. Conclusions: The striking similarities between these two types of prostate cancers rules out a major impact of ERG on tumor aggressiveness in early, not hormonally treated cancer. The marked difference in AR levels between ERG-positive and -negative cancers supports a systematic difference in potential response to hormonal therapy as previously observed in clinical trials. Clin Cancer Res; 17(18); 5878–88. ©2011 AACR.

Limited data exist on the impact of the site of metastases on survival in patients with stage IV prostate cancer (PCa).To investigate the role of metastatic phenotype at presentation on mortality in stage IV PCa.Overall, 3857 patients presenting with metastatic PCa between 1991 and 2009, included in the Surveillance Epidemiology and End Results-Medicare database were evaluated.Overall and cancer-specific survival rates were estimated in the overall population and after stratifying patients according to the metastatic site (lymph node [LN] alone, bone, visceral, or bone plus visceral). Multivariable Cox regression analyses tested the relationship between the site of metastases and survival. All analyses were repeated in a subcohort of patients with a single metastatic site involved.Respectively, 2.8%, 80.2%, 6.1%, and 10.9% of patients presented with LN, bone, visceral, and bone plus visceral metastases at diagnosis. Respective median overall survival and cancer-specific survival were 43 mo and 61 mo for LN metastases, 24 mo and 32 mo for bone metastases, 16 mo and 26 mo for visceral metastases, and 14 mo and 19 mo for bone plus visceral metastases (p<0.001). In multivariable analyses, patients with visceral metastases had a significantly higher risk of overall and cancer-specific mortality versus those with exclusively LN metastases (p<0.001). The unfavorable impact of visceral metastases persisted in the oligometastatic subgroup. Our study is limited by its retrospective design.Visceral involvement represents a negative prognostic factor and should be considered as a proxy of more aggressive disease in patients presenting with metastatic PCa. This parameter might indicate the need for additional systemic therapies in these individuals.Patients with visceral metastases should be considered as affected by more aggressive disease and might benefit from the inclusion in clinical trials evaluating novel molecules.

In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy. To provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP). We searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update. We found new evidence for several topics. Up to 40% of the cross-sectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence. This update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes. Based on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time.

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.

The optimal management strategy for men with newly diagnosed clinically localized prostate cancer remains a matter of debate. Numerous series have reported cancer control and quality-of-life (QoL) outcomes following treatment with radical prostatectomy (RP). Critically review published oncologic and functional outcomes after RP, and evaluate factors associated with these outcome measures. A review of the literature was performed using the Medline and Web of Sciences databases. Relevant reports published between 1980 and 2011 identified using the keywords prostate cancer, radical prostatectomy, prostate-specific antigen, biochemical recurrence, incontinence, and erectile dysfunction were reviewed and summarized. Cancer control rates following RP largely depend on the definition of treatment efficacy. While up to 40% of men have been reported to experience postoperative biochemical recurrence on long-term follow-up, death from prostate cancer has been noted in <10% of men at 15 yr after surgery in contemporary series. For men with high-risk disease, surgery affords pathologic staging, thereby facilitating the selective application of secondary therapies, and has been associated with decreased mortality risk versus radiation in retrospective series. Reported functional outcomes after surgery, particularly urinary continence and erectile dysfunction, have varied greatly to date. These assessments have been limited by nonstandardized reporting methodology. The use of robot-assisted radical prostatectomy has increased in recent years, and while follow-up is thus far short, available data do not suggest the superiority of either approach in terms of functional or oncologic outcomes. RP is associated with excellent long-term cancer control. Continued efforts to conduct prospective assessments of postoperative functional outcomes are necessary using validated QoL instruments. The importance of surgical approach will also require further study, incorporating comparative oncologic, functional, and economic data.

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.

Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. To test the accuracy of serum isoform [−2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests—in discriminating between patients with and without PCa. This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA. The study is registered at http://www.controlled-trials.com, ref. ISRCTN04707454.

High-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory.To develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors.We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers.Retropubic radical prostatectomy with pelvic lymphadenectomy.Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (GS) (2-7 vs 8-10), and prostate-specific antigen (PSA; ≤ 20 ng/ml vs > 20 ng/ml). The first "extended" model includes all seven possible combinations; the second "simplified" model includes three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (GS 8-10 in combination with at least one other high-risk factor). The predictive accuracy of the models was summarized and compared. Survival estimates and clinical and pathologic outcomes were compared between the three subgroups.The simplified model yielded an R(2) of 33% with a 5-yr area under the curve (AUC) of 0.70 with no significant loss of predictive accuracy compared with the extended model (R(2): 34%; AUC: 0.71). The 5- and 10-yr PCSS rates were 98.7% and 95.4%, 96.5% and 88.3%, 88.8% and 79.7%, for the good, intermediate, and poor prognosis subgroups, respectively (p = 0.0003). Overall survival, clinical progression-free survival, and histopathologic outcomes significantly worsened in a stepwise fashion from the good to the poor prognosis subgroups. Limitations of the study are the retrospective design and the long study period.This study presents an intuitive and easy-to-use stratification of high-risk PCa into three prognostic subgroups. The model is useful for counseling and decision making in the pretreatment setting.

The cell cycle progression score is associated with prostate cancer outcomes in various clinical settings. However, previous studies of men treated with radical prostatectomy evaluated cell cycle progression scores generated from resected tumor tissue. We evaluated the prognostic usefulness of the score derived from biopsy specimens in men treated with radical prostatectomy.We evaluated the cell cycle progression score in cohorts of patients from the Martini Clinic (283), Durham Veterans Affairs Medical Center (176) and Intermountain Healthcare (123). The score was derived from simulated biopsy (Martini Clinic) or diagnostic biopsy (Durham Veterans Affairs Medical Center and Intermountain Healthcare) and evaluated for an association with biochemical recurrence and metastatic disease.In all 3 cohorts the cell cycle progression score was associated with biochemical recurrence and metastatic disease. The association with biochemical recurrence remained significant after adjusting for other prognostic clinical variables. On combined analysis of all cohorts (total 582 patients) the score was a strong predictor of biochemical recurrence on univariate analysis (HR per score unit 1.60, 95% CI 1.35-1.90, p=2.4×10(-7)) and multivariate analysis (HR per score unit 1.47, 95% CI 1.23-1.76, p=4.7×10(-5)). Although there were few events (12), the cell cycle progression score was the strongest predictor of metastatic disease on univariate analysis (HR per score unit 5.35, 95% CI 2.89-9.92, p=2.1×10(-8)) and after adjusting for clinical variables (HR per score unit 4.19, 95% CI 2.08-8.45, p=8.2×10(-6)).The cell cycle progression score derived from a biopsy sample was associated with adverse outcomes after surgery. These results indicate that the score can be used at disease diagnosis to better define patient prognosis and enable more appropriate clinical care.

Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this setting. To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer. A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden. Radical prostatectomy and extended pelvic lymphadenectomy. Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined. Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up. Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity. Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients.

In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value. To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes. A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014–2020), was conducted. PSMA-RGS. Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo. Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2–16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III–IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02–1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08–1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23–2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31–3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group. As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET–avid lesions located in the pelvis. We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow.

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.

To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables.We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records.In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P < 0.001).The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.

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.

This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP).To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided.A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field.In contemporary series, PSM are reported in 11-38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS).PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made.

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.

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.

Purpose Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool. Patients and Methods Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram. Results Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P &lt; .001), elevated CCI score (P &lt; .001) and treatment type (EBRT v RP, P &lt; .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years. Conclusion Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.

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.

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 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.

The TNM staging system represents the cornerstone for classifying patients with upper tract urothelial carcinoma (UTUC). We tested the prognostic impact of pT and pN stages on cancer-specific mortality (CSM) in a large population-based cohort of surgically treated patients with UTUC.Our analyses relied on 2299 patients treated with nephroureterectomy (NU) or segmental ureterectomy (SU) for UTUC within nine Surveillance, Epidemiology and End Results registries between 1988 and 2004. CSM rates after surgery were graphically explored using Kaplan-Meier plots. Univariable and multivariable Cox regression models tested the effect of pT and pN stages on CSM, after adjusting for tumour grade, age, gender, primary tumour location, type and year of surgery.Five years after surgery, the overall CSM-free survival rate was 77.6%. The 5-year CSM-free survival rates of pT(1)N(0) (n=739), pT(2)N(0) (n=422), pT(3)N(0) (n=691), pT(4)N(0) (n=190) and any T N(1-3) (n=257) were, respectively, 93.5 versus 86.2 versus 64.5 versus 54.7 versus 35.0%. The 5-year CSM-free survival rates of pT(1-2)N(1-3) (n=41) and pT(3-4)N(1-3) (n=216) patients were, respectively, 68.9% and 28.7% (p=0.006). In multivariable analyses, pT and pN stages (p<0.001), as well as tumour grade (p<0.001), achieved independent predictor status. Advanced age adversely affected CSM-free survival (p=0.001). Conversely, tumour location, gender, year and type of surgery did not exert independent predictor status.Durable cancer control can be expected in patients treated with NU or SU for organ-confined (pT(1-2)) UTUC. Conversely, the presence of non-organ-confined (pT(3-4)) disease and/or of nodal metastases (pN(1-3)) exerts a profound detrimental effect on CSM-free survival.

To perform a population-based analysis of the potential staging or prognostic value (or both) of lymph node dissection (LND) in patients without nodal metastases vs no LND. In several previous reports, LND in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy (NU) was associated with better survival relative to no LND (pN(x)), even in the absence of pathologically confirmed nodal metastases (pN(0)).Within the surveillance, epidemiology, and end results database, we identified 2824 patients treated with NU for UTUC between 1988 and 2004. CSM rates after NU were graphically explored using Kaplan-Meier plots. Univariable and multivariable Cox regression models tested the effect of N(0) vs N(x) stage on CSM, after adjusting for T stage, tumor grade, age, gender, primary tumor location, type, and year of surgery.The CSM-free survival rate at 5 years after NU was 81.2% and 77.8% respectively for pN(0) and pN(x) patients. In univariable analyses pN(x) vs pN(0) status was not associated with worse survival (HR: 1.19; P = .09). After adjustment for all covariates, pN(x) vs pN(0) status still failed to achieve independent predictor status (HR: 0.99; P = .9).We found no survival benefit related to the performance of LND in pN(0) patients, relative to pN(x) patients. Lack of standardized criteria for patients' selection for LND and for pathological lymph node specimen evaluation represents some of the explanation for the observed discrepancy between the current finding and previous findings.

Sexual dysfunction is common in patients who undergo radical prostatectomy (RP) for prostate cancer (PCa). Review the available literature concerning prevention of, and management strategies for, post-RP sexual dysfunction in terms of postoperative treatments for erectile function (EF), sexual desire (SD), and orgasmic function (OF) impairment. A literature search was performed using Google and PubMed databases for English language original and review articles either published or e-published up to November 2011. We propose a rational description of many of the clinically available preventive and therapeutic strategies for the preservation and recovery of post-RP EF. A huge amount of preclinical data show that tissue damage ultimately leads to structural alterations, and the literature stresses that rehabilitation and treatment are undoubtedly better than leaving the erectile tissue to its unassisted fate; likewise, the timing of any rehabilitation and treatment is of major clinical importance. However, no specific recommendation emerges regarding the structure of the optimal rehabilitation or treatment regimen. The role of postoperative erectile dysfunction (ED) treatment of those patients who received a non–nerve-sparing RP was also extensively discussed. The literature almost completely lacks a systematic and comprehensive debate about SD (ie, low libido) and OF (ie, decreased intensity of orgasm, dysorgasmia, and climacturia) in patients undergoing RP. Psychological and sexual counseling is of major importance to improve any rehabilitation and treatment of postoperative EF, SD, and OF impairment. Despite the great number of possible rehabilitation approaches proposed, these approaches should be considered only as strategies, since incontrovertible evidence of their effectiveness for improving natural EF recovery is limited. Conversely, numerous effective therapeutic options are available for treating post-RP ED. SD and OF have not yet been fully assessed in patients who underwent RP.

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.

No AccessJournal of UrologyAdult Urology1 Jun 2011Clinical Evaluation of the PCA3 Assay in Guiding Initial Biopsy Decisions Alexandre de la Taille, Jacques Irani, Markus Graefen, Felix Chun, Theo de Reijke, Paul Kil, Paolo Gontero, Alain Mottaz, and Alexander Haese Alexandre de la TailleAlexandre de la Taille CHU Henri Mondor, Paris, France Nothing to disclose. More articles by this author , Jacques IraniJacques Irani CHU La Milétrie, Poitiers, France Financial interest and/or other relationship with Gen-Probe. More articles by this author , Markus GraefenMarkus Graefen Martini-Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author , Felix ChunFelix Chun Department of Urology, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author , Theo de ReijkeTheo de Reijke Academic Medical Center, Amsterdam, the Netherlands Nothing to disclose. More articles by this author , Paul KilPaul Kil St. Elisabeth Ziekenhuis, Tilburg, the Netherlands Nothing to disclose. More articles by this author , Paolo GonteroPaolo Gontero Ospedale Molinette, Università di Torino, Turin, Italy Nothing to disclose. More articles by this author , Alain MottazAlain Mottaz Gene Predictis SA, Granges-Paccot, Switzerland Nothing to disclose. More articles by this author , and Alexander HaeseAlexander Haese Martini-Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.01.075AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. Materials and Methods: A European, prospective, multicenter study enrolled men with a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digital rectal examination first catch urine was collected. PCA3 scores were determined using the PROGENSA® PCA3 assay and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. Results: In 516 men the positive biopsy rate was 40%. An increasing PCA3 score corresponded with an increasing probability of a positive biopsy. The mean PCA3 score was higher in men with a positive vs a negative biopsy (69.6 vs 31.0, median 50 vs 18, p <0.0001). The PCA3 score was independent of age, total prostate specific antigen and prostate volume. The PCA3 score (cutoff of 35) had a sensitivity of 64% and specificity of 76%. ROC analysis showed a significantly higher AUC for the PCA3 score vs total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. The PCA3 score was significantly higher in men with biopsy Gleason score 7 or greater vs less than 7, greater than 33% vs 33% or fewer positive cores and significant vs indolent prostate cancer. Inclusion of PCA3 in multivariable models increased their predictive accuracy by up to 5.5%. Conclusions: The PROGENSA PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness. References 1 : Over- and underdiagnosis of prostate cancer: the dangers. Eur Urol Suppl2006; 5: 511. Google Scholar 2 : Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med2004; 350: 2239. Google Scholar 3 : Screening for prostate cancer. Eur J Cancer2005; 41: 825. Google Scholar 4 : Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study. J Urol2003; 169: 125. Link, Google Scholar 5 : Prostate biopsy. Minerva Urol Nefrol2003; 55: 205. Google Scholar 6 : Current status of transrectal ultrasound-guided prostate biopsy in the diagnosis of prostate cancer. Clin Radiol2006; 61: 142. Google Scholar 7 : Incidence of acute prostatitis caused by extended-spectrum β-lactamase-producing escherichia coli after transrectal prostate biopsy. Urology2009; 74: 119. Google Scholar 8 : Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant biopsies of the prostate within a population-based screening program. Urology2002; 60: 826. Google Scholar 9 : PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology2007; 69: 532. Google Scholar 10 : Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol2008; 54: 1081. Google Scholar 11 : PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol2008; 179: 1587. Link, Google Scholar 12 : PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol2008; 179: 1804. Link, Google Scholar 13 : PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol2008; 180: 1975. Link, Google Scholar 14 Product package insert for PROGENSA PCA3 Assay. Google Scholar 15 : Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA1994; 271: 368. Google Scholar 16 : Characteristics of insignificant clinical T1c prostate tumors: A contemporary analysis . Cancer2004; 101: 2001. Google Scholar 17 : Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate2008; 68: 1215. Google Scholar 18 : Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program. J Urol2010; 183: 534. Link, Google Scholar 19 : Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate2010; 70: 10. Google Scholar 20 : Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram. Eur Urol2009; 56: 659. Google Scholar 21 : Evaluating a new marker's predictive contribution. Clin Cancer Res2004; 10: 822. Google Scholar 22 : Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst2003; 95: 634. Google Scholar 23 Prostate Cancer Prevention Trial risk calculator. http://deb.uthscsa.edu/URORiskCalc/Pages/calcsPCA3.jsp. Accessed April 2010. Google Scholar 24 : Prostate biopsy: current status and limitations. Rev Urol2007; 9: 93. Google Scholar 25 : Probability of prostate cancer at various levels of per cent free prostate specific antigen in Japanese men with total PSA of 4.1-10.0 ng/ml. Prostate Cancer Prostatic Dis2002; 5: 115. Google Scholar 26 : The free-to-total prostate specific antigen ratio improves the specificity of prostate specific antigen in screening for prostate cancer in the general population. J Urol1997; 157: 2191. Link, Google Scholar 27 : APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem2006; 52: 1089. Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byPloussard G and de la Taille A (2014) Does PCA3 Really Help Urologists?Urology Practice, VOL. 1, NO. 2, (57-61), Online publication date: 1-Jul-2014.Chevli K, Duff M, Walter P, Yu C, Capuder B, Elshafei A, Malczewski S, Kattan M and Jones J (2013) Urinary PCA3 as a Predictor of Prostate Cancer in a Cohort of 3,073 Men Undergoing Initial Prostate BiopsyJournal of Urology, VOL. 191, NO. 6, (1743-1748), Online publication date: 1-Jun-2014.Scattoni V, Lazzeri M, Lughezzani G, De Luca S, Passera R, Bollito E, Randone D, Abdollah F, Capitanio U, Larcher A, Lista G, Gadda G, Bini V, Montorsi F and Guazzoni G (2013) Head-to-Head Comparison of Prostate Health Index and Urinary PCA3 for Predicting Cancer at Initial or Repeat BiopsyJournal of Urology, VOL. 190, NO. 2, (496-501), Online publication date: 1-Aug-2013.Bradley L, Palomaki G, Gutman S, Samson D and Aronson N (2013) Comparative Effectiveness Review: Prostate Cancer Antigen 3 Testing for the Diagnosis and Management of Prostate CancerJournal of Urology, VOL. 190, NO. 2, (389-398), Online publication date: 1-Aug-2013.Ploussard G (2012) How Much Should We Pursue an Elevated Prostate Specific Antigen?Journal of Urology, VOL. 188, NO. 5, (1658-1659), Online publication date: 1-Nov-2012.Crawford E, Rove K, Trabulsi E, Qian J, Drewnowska K, Kaminetsky J, Huisman T, Bilowus M, Freedman S, Glover W and Bostwick D (2012) Diagnostic Performance of PCA3 to Detect Prostate Cancer in Men with Increased Prostate Specific Antigen: A Prospective Study of 1,962 CasesJournal of Urology, VOL. 188, NO. 5, (1726-1731), Online publication date: 1-Nov-2012. Volume 185Issue 6June 2011Page: 2119-2125 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordsbiopsyprostatic neoplasmsprostate cancer antigen 3humanprostate-specific antigensensitivity and specificityAcknowledgmentsIsmar Healthcare NV provided assistance. The PROGENSA PCA3 assay was performed by Biomnis, Creteil, France; Labor Limbach, Heidelberg, Germany; NovioGendix, Nijmegen, The Netherlands; Laboratorio Analisi Ospedale Gradenigo, Torino, Italy and Gene Predictis SA, Granges-Paccot, Switzerland.MetricsAuthor Information Alexandre de la Taille CHU Henri Mondor, Paris, France Nothing to disclose. More articles by this author Jacques Irani CHU La Milétrie, Poitiers, France Financial interest and/or other relationship with Gen-Probe. More articles by this author Markus Graefen Martini-Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author Felix Chun Department of Urology, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author Theo de Reijke Academic Medical Center, Amsterdam, the Netherlands Nothing to disclose. More articles by this author Paul Kil St. Elisabeth Ziekenhuis, Tilburg, the Netherlands Nothing to disclose. More articles by this author Paolo Gontero Ospedale Molinette, Università di Torino, Turin, Italy Nothing to disclose. More articles by this author Alain Mottaz Gene Predictis SA, Granges-Paccot, Switzerland Nothing to disclose. More articles by this author Alexander Haese Martini-Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany Nothing to disclose. More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

Chronic kidney disease (CKD) is a worldwide health threat associated with increased cardiovascular disease and mortality. To examine postoperative CKD in patients with small renal masses (SRMs) treated with partial nephrectomy (PN) or radical nephrectomy (RN). A US National Cancer Institute Surveillance Epidemiology and End Results (SEER)–Medicare-linked retrospective cohort of 4633 T1aN0M0 renal cell carcinoma (RCC) patients who underwent PN or RN. The primary outcome of interest was the onset of CKD stage ≥3. Secondary end points comprised acute renal failure (ARF), chronic renal insufficiency (CRI), anemia in CKD, and end-stage renal disease (ESRD). Kaplan-Meier and Cox regression analyses were performed. Postpropensity matching resulted in 840 RN and PN patients. In multivariable analyses, RN patients were 1.9-, 1.4-, 1.8-, and 1.8-fold more likely to have an occurrence of CKD, ARF, CRI, and anemia in CKD, respectively (all p ≤ 0.004). The risk of ESRD between treatment groups failed to achieve statistical significance (p = 0.06). PN is associated with more favorable postoperative renal function outcomes relative to RN in the setting of SRMs.

Abstract Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the first high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing. Comparative analyses identified more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show significant differences based on the TMPRSS2–ERG rearrangement status. We propose the hypermethylation of miR-26a as an alternative pathway of ERG rearrangement-independent EZH2 activation. The observed increase in differential methylation events in fusion–negative tumors can explain the tumorigenic process in the absence of genomic rearrangements. Significance: In contrast to TMPRSS2–ERG-rearranged tumors, the pathomechanism for gene fusion–negative tumors is completely unclear. Using a sequencing-based approach, our work uncovers significant global epigenetic alterations in TMPRSS2–ERG gene fusion–negative tumors and provides a mechanistic explanation for the tumor formation process. Cancer Discov; 2(11); 1024–35. ©2012 AACR. Read the Commentary on this article by Alumkal and Herman, p. 979. This article is featured in Highlights of This Issue, p. 961

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.

Key Points Polyphosphate-activated coagulation factor XII drives prostate cancer-associated venous thrombosis. Targeting the polyphosphate/factor XII pathway reduces procoagulant activity in prostate cancer patient plasma and may permit safe anticoagulation.

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.

Sexual dysfunction is common in patients following radical prostatectomy (RP) for prostate cancer (PCa).To review the available literature concerning prevention and management strategies for post-RP erectile function (EF) impairment in terms of preoperative patient characteristics and intra- and postoperative factors that may influence EF recovery.A literature search was performed using Google and PubMed database for English-language original and review articles either published or e-published up to November 2011.The literature demonstrates great inconsistency in what constitutes normal EF before surgery and what a man may consider a normal erection after RP. The use of validated psychometric instruments with recognised cut-offs for normalcy and severity during the pre- and postoperative evaluation should be routinely considered. Therefore, a comprehensive discussion with the patient about the true prevalence of postoperative erectile dysfunction (ED), the concept of spontaneous or pharmacologically assisted erections, and the difference between "back to baseline" EF and "erections adequate enough to have successful intercourse" clearly emerge as key issues in the eventual understanding of the prevention of ED and promotion of satisfactory EF recovery post-RP. Patient factors (including age, baseline EF, and status of comorbid conditions), cancer selection (unilateral vs bilateral nerve sparing), type of surgery (ie, intra- vs inter- vs extrafascial surgeries), surgical techniques (ie, open, laparoscopic, and robot-assisted RP), and surgeon factors (ie, surgical volume and surgical skill) represent the key significant contributors to EF recovery.The complexity of the issues discussed throughout this review culminates in the simple concept that optimal outcomes are achieved by the careful choice of the correct patient for the correct type of surgery.

Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction.We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries.At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy.The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

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. Link, Google Scholar 3 : Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer. Urology1997; 50: 93. Google Scholar 4 : Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA2005; 294: 433. Google Scholar 5 : Natural history of progression after PSA elevation following radical prostatectomy. JAMA1999; 281: 1591. Crossref, Medline, Google Scholar 6 : Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality. J Urol2006; 176: 1404. Link, Google Scholar 7 : Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet2005; 366: 572. Google Scholar 8 : Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA2006; 296: 2329. Google Scholar 9 : Adjuvant weekly docetaxel for patients with high risk prostate cancer after radical prostatectomy: a multi-institutional pilot study. J Urol2007; 177: 1777. Link, Google Scholar 10 : Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol2006; 7: 472. Google Scholar 11 : A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst1998; 90: 766. Crossref, Medline, Google Scholar 12 : Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol1999; 17: 1499. Crossref, Medline, Google Scholar 13 : Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol2005; 23: 7005. 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 ...

Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP.The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach.A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper.RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology.Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients.

The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial.To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated.We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins.All patients underwent radical retropubic prostatectomy and PLND.Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates.Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram.Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.

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.

Delaying definitive therapy unfavourably affects outcomes in many malignancies. Diagnostic, psychological, and logistical reasons but also active surveillance (AS) strategies can lead to treatment delay, an increase in the interval between the diagnosis and treatment of prostate cancer (PCa). To review and summarise the current literature on the impact of treatment delay on PCa oncologic outcomes. A comprehensive search of PubMed and Embase databases until 30 September 2012 was performed. Studies comparing pathologic, biochemical recurrence (BCR), and mortality outcomes between patients receiving direct and delayed curative treatment were included. Studies presenting single-arm results following AS were excluded. Seventeen studies were included: 13 on radical prostatectomy, 3 on radiation therapy, and 1 combined both. A total of 34 517 PCa patients receiving radical local therapy between 1981 and 2009 were described. Some studies included low-risk PCa only; others included a wider spectrum of disease. Four studies found a significant effect of treatment delay on outcomes in multivariate analysis. Two included low-risk patients only, but it was unknown whether AS was applied or repeat biopsy triggered active therapy during AS. The two other studies found a negative effect on BCR rates of 2.5–9 mo delay in higher risk patients (respectively defined as any with T ≥2b, prostate-specific antigen >10, Gleason score >6, >34–50% positive cores; or D’Amico intermediate risk-group). All studies were retrospective and nonrandomised. Reasons for delay were not always clear, and time-to-event analyses may be subject to bias. Treatment delay of several months or even years does not appear to affect outcomes of men with low-risk PCa. Limited data suggest treatment delay may have an impact on men with non–low-risk PCa. Most AS protocols suggest a confirmatory biopsy to avoid delaying treatment in those who harbour higher risk disease that was initially misclassified.

In 2001, Rocco et al. described a surgical technique whose aim was the reconstruction of the posterior musculofascial plate after radical prostatectomy (RP) to improve early return to urinary continence. Since then, many surgeons have applied this technique-either as it was described or with some modification-to open, laparoscopic, and robot-assisted RP.To review the outcomes reported in comparative studies analysing the influence of reconstruction of the posterior aspect of the rhabdosphincter after RP. The main outcome evaluated was urinary continence at 3-7 d, 30-45 d, 90 d, 180 d, and 1 yr after catheter removal.A systematic review of the literature was performed in November 2011, searching the Medline, Embase, Scopus, and Web of Science databases. A "free-text" protocol using the terms posterior reconstruction of the rhabdosphincter, posterior rhabdosphincter, and early continence was applied. Studies published only as abstracts and reports from meetings were not included in this review. One thousand seven records were retrieved from the Medline database, 1541 from the Embase database, 1357 from the Scopus database, and 1041 from the Web of Science database. The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. Only papers evaluating use of this technique as the only technical modification among the groups were included. A cumulative analysis was conducted using Review Manager v.5.1 software (Cochrane Collaboration, Oxford, UK).Eleven studies were identified in the literature search, including two randomised controlled trials (RCTs), which were negative studies. The cumulative analysis of comparative studies showed that reconstruction of the posterior musculofascial plate improves early return of continence within the first 30 d after RP (p=0.004), while continence rates 90 d after surgery are not affected by use of the reconstruction technique. The statistical significance of the reconstruction seems to decrease when higher continence rates are reported. Use of posterior rhabdosphincter reconstruction does not seem to be related to positive surgical margin (PSM) rates or with complications like acute urinary retention (AUR) and bladder neck stricture (BNS). Some studies suggested lower anastomotic leakage rates with the posterior musculofascial plate reconstruction technique.The role of reconstruction of the posterior musculofascial plate in terms of earlier continence recovery is encouraging but still controversial. Methodological flaws and poor surgical standardisation seem to be the major causes. In two RCTs and one parallel (not randomised) group trial, posterior rhabdosphincter reconstruction offered no significant advantage for return of early continence after RP. No significant complications related to the posterior musculofascial plate reconstruction technique have been reported so far. A multicentre RCT is necessary to clarify the possible role of the technique in terms of earlier continence recovery.

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.

No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone.Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM).Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P<0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM (P<0.001).Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR.

Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease.To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa.Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8-10, clinical stage ≥ T3) were identified.All patients underwent RP and pelvic lymph node dissection.Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more).Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (≤ 59 yr) with no comorbidities, regardless of the number of risk factors (10-yr CSM and OCM 6.9-12.8% and 5.5-6.3%, respectively). The main limitation was the lack of patients managed conservatively.Even in the context of high-risk PCa, long-term CSM after RP is modest and represents the leading cause of death only in young, healthy patients. Conversely, older and sicker patients with multiple risk factors are at the highest risk of dying from OCM while sharing very low CSM rates.

To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI.The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis.Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively).%p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness.

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.

No AccessJournal of UrologyAdult Urology1 Mar 2015Shear Wave Elastography for Localization of Prostate Cancer Lesions and Assessment of Elasticity Thresholds: Implications for Targeted Biopsies and Active Surveillance Protocols Katharina Boehm, Georg Salomon, Burkhard Beyer, Jonas Schiffmann, Kathrin Simonis, Markus Graefen, and Lars Budaeus Katharina BoehmKatharina Boehm Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany Equal study contribution. More articles by this author , Georg SalomonGeorg Salomon Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany Equal study contribution. More articles by this author , Burkhard BeyerBurkhard Beyer Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author , Jonas SchiffmannJonas Schiffmann Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author , Kathrin SimonisKathrin Simonis Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany More articles by this author , Markus GraefenMarkus Graefen Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author , and Lars BudaeusLars Budaeus Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.09.100AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Shear wave elastography allows the detection of cancer by using focused ultrasound pulses for locally deforming tissue. The differences in tissue elasticity and stiffness have been used increasingly in breast cancer imaging and help detect potential tumor lesions in the prostate. In this study we localized prostate cancer lesions using shear wave elastography before radical prostatectomy and assessed the examiner independent elasticity threshold for cancer foci detection. Materials and Methods: Shear wave elastography scanning of the whole prostate was performed before radical prostatectomy in 60 consecutive patients with high, intermediate and low risk disease. Localization of suspected lesions and density threshold (kPa) were recorded in up to 12 areas and resulted in 703 different fields. Shear wave elastography findings were correlated with final pathology. Initially 381 areas were used to establish shear wave elastography cutoffs (development cohort 32 patients). Subsequently these cutoffs were validated in 322 areas (validation cohort 28 patients). Results: Using shear wave elastography significant differences were recorded for the elasticity of benign tissue vs prostate cancer nodules at 42 kPa (range 29 to 71.3) vs 88 kPa (range 54 to 132) (all p <0.001). Median cancer lesion diameter was 26 mm (range 18 to 41). Applying the most informative cutoff of 50 kPa to the validation cohort resulted in 80.9% and 69.1% sensitivity and specificity, respectively, and 74.2% accuracy for detecting cancer nodules based on final pathological finding. The corresponding positive and negative predictive values were 67.1% and 82.2%, respectively. Conclusions: Shear wave elastography allows the identification of cancer foci based on shear wave elastography differences. Moreover, reliable cutoffs for this approach can be established, allowing examiner independent localization of prostate cancer foci. References 1 : EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol2014; 65: 124. Google Scholar 2 : Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy. Urology2002; 60: 836. Google Scholar 3 : Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases. Breast Cancer Res Treat2011; 129: 89. Google Scholar 4 : Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification. Br J Cancer2012; 107: 224. Google Scholar 5 : The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: a prospective study of 353 patients. J Urol2012; 187: 2039. Link, Google Scholar 6 : Evaluation of prostate cancer detection with ultrasound real-time elastography: a comparison with step section pathological analysis after radical prostatectomy. Eur Urol2008; 54: 1354. Google Scholar 7 : Protocol for the examination of specimens from patients with carcinoma of the prostate gland. Arch Pathol Lab Med2009; 133: 1568. Google Scholar 8 : Screening and prostate-cancer mortality in a randomized European study. N Engl J Med2009; 360: 1320. Google Scholar 9 : Antibiotic prophylaxis for transrectal prostate biopsy. Cochrane Database Syst Rev2011; 5: CD006576. Google Scholar 10 : Infectious complications and hospital admissions after prostate biopsy in a European randomized trial. Eur Urol2012; 61: 1110. Google Scholar 11 : Shear wave ultrasound elastography of the prostate: initial results. Ultrasound Q2012; 28: 13. Google Scholar 12 : A learning curve assessment of real-time sonoelastography of the prostate. World J Urol2014; 32: 317. Google Scholar 13 : Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert scales. Radiology2013; 269: 482. Google Scholar 14 : Characterization of prostate lesions as benign or malignant at multiparametric MR imaging: comparison of three scoring systems in patients treated with radical prostatectomy. Radiology2014; 272: 446. Google Scholar 15 : Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics. BJU Int2013; 112: 568. Google Scholar 16 : The clinical value of diffusion-weighted imaging in combination with T2-weighted imaging in diagnosing prostate carcinoma: a systematic review and meta-analysis. AJR Am J Roentgenol2012; 199: 103. Google Scholar 17 : Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2-weighted, dynamic contrast-enhanced and diffusion-weighted imaging. BJU Int2011; 107: 1411. Google Scholar 18 : Diffusion-weighted magnetic resonance imaging detects significant prostate cancer with high probability. J Urol2014; 192: 737. Link, Google Scholar 19 : Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation. BJU Int2006; 98: 329. Google Scholar 20 : Pathological outcomes in men with low risk and very low risk prostate cancer: implications on the practice of active surveillance. J Urol2013; 190: 1218. Link, Google Scholar 21 : Pathological and biochemical outcomes after radical prostatectomy in men with low-risk prostate cancer meeting the Prostate Cancer International: Active Surveillance criteria. BJU Int2013; 111: 914. Google Scholar 22 : Upgrading of Gleason score and prostate volume: a clinicopathological analysis. BJU Int2013; 111: 1310. Google Scholar 23 : The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized disease. BJU Int2010; 105: 472. Google Scholar 24 : Potentials and limitations of real-time elastography for prostate cancer detection: a whole-mount step section analysis. ScientificWorldJournal2012; 2012: 193213. Google Scholar 25 : Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol1974; 111: 58. Abstract, Google Scholar 26 : Intermixed normal tissue within prostate cancer: effect on MR imaging measurements of apparent diffusion coefficient and T2-sparse versus dense cancers. Radiology2008; 249: 900. Google Scholar 27 : Transition zone prostate cancer: detection and localization with 3-T multiparametric MR imaging. Radiology2013; 266: 207. Google Scholar 28 : The zonal anatomy of the prostate. Prostate1981; 2: 35. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byMannaerts C, Wildeboer R, Remmers S, van Kollenburg R, Kajtazovic A, Hagemann J, Postema A, van Sloun R, J. Roobol M, Tilki D, Mischi M, Wijkstra H and Salomon G (2019) Multiparametric Ultrasound for Prostate Cancer Detection and Localization: Correlation of B-mode, Shear Wave Elastography and Contrast Enhanced Ultrasound with Radical Prostatectomy SpecimensJournal of Urology, VOL. 202, NO. 6, (1166-1173), Online publication date: 1-Dec-2019.Wei C, Li C, Szewczyk-Bieda M, Upreti D, Lang S, Huang Z and Nabi G (2018) Performance Characteristics of Transrectal Shear Wave Elastography Imaging in the Evaluation of Clinically Localized Prostate Cancer: A Prospective StudyJournal of Urology, VOL. 200, NO. 3, (549-558), Online publication date: 1-Sep-2018.Schiffmann J, Grindei M, Tian Z, Yassin D, Steinwender T, Leyh-Bannurah S, Randazzo M, Kwiatkowski M, Karakiewicz P, Hammerer P and Manka L (2016) Limitations of Elastography Based Prostate BiopsyJournal of Urology, VOL. 195, NO. 6, (1731-1736), Online publication date: 1-Jun-2016.Steers W (2014) This Month in Adult UrologyJournal of Urology, VOL. 193, NO. 3, (747-748), Online publication date: 1-Mar-2015. Volume 193Issue 3March 2015Page: 794-800 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordselasticity imaging techniquesprostatectomymagnetic resonance imagingprostatic neoplasmsearly detection of cancerAcknowledgmentsSuperSonic Imagine, Aix-en-Provence, France, provided an Aixplorer ultrasound system.MetricsAuthor Information Katharina Boehm Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany Equal study contribution. More articles by this author Georg Salomon Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany Equal study contribution. More articles by this author Burkhard Beyer Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author Jonas Schiffmann Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author Kathrin Simonis Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany More articles by this author Markus Graefen Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author Lars Budaeus Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, Hamburg, Germany More articles by this author Expand All Advertisement PDF downloadLoading ...

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Long-term cancer control outcomes in clinically high-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP) remain unknown. To report on long-term biochemical recurrence (BCR)–free survival, clinical recurrence (CR)–free survival, and salvage therapy rates in these patients. Given the heterogeneity of high-risk patients, a second objective was to stratify them according to their BCR risk (using preoperative parameters), in an effort to counsel them better preoperatively regarding their cancer control outcomes. We evaluated 1100 D’Amico high-risk PCa patients who underwent RARP between 2002 and 2013 at three tertiary care centers. Outcomes consisted of BCR-free survival, CR-free survival, and salvage therapy rates. Regression tree analysis stratified patients into novel risk groups based on preoperative characteristics and corresponding BCR risk. Kaplan-Meier curves estimated BCR-free survival, CR-free survival, and salvage therapy rates in the entire cohort and after stratification according to the novel risk groups (RGs). Median age and prostate-specific antigen (PSA) were 63 yr and 6.5 ng/ml, respectively. Biopsy Gleason score (GS) was ≥8 in 57.7%. Mean follow-up was 53 mo (median: 49 mo). At 10 yr, BCR-free survival, CR-free survival, and salvage therapy rates were 50%, 87%, and 37%, respectively. Regression tree analysis stratified patients into five novel RGs): RG1, very low risk (GS ≤6); RG2, low risk (PSA ≤10 ng/ml; GS: 7); RG3, intermediate risk (PSA ≤10 ng/ml; GS ≥8); RG4, high risk (PSA >10 ng/ml; GS: 7); RG5, very high risk (PSA >10 ng/ml; GS ≥8). In these RGs, the 10-yr BCR-free survival rates were 86%, 70%, 36%, 31%, and 26% (p < 0.001), respectively; the 10-yr CR-free survival rates were 99%, 96%, 85%, 67%, and 55% (p < 0.001), respectively; and the 10-yr salvage therapy rates were 9.8%, 16%, 42%, 47%, and 64% (p < 0.001), respectively. Most patients with clinically high-risk PCa treated with RARP alone remain CR free at long term. Nonetheless, almost 37% of the patients at 10 yr require salvage therapy. Our novel tool allows accurate stratification of these heterogeneous patients according to their BCR, CR, and salvage therapy risks. This may help inform patients preoperatively about their cancer control outcomes postoperatively. Robot-assisted radical prostatectomy confers lasting long-term oncologic control in most high-risk prostate cancer patients. Our novel risk grouping might serve as a useful tool for setting expectations and counseling patients regarding their cancer control outcomes.

Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes.To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT).PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis.The SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence.The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses.At a median follow-up of 70 (interquartile range: 48-98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17-0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3-99.6) and 95.7% (95% CI: 93.2-97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort.MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting.Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

Multimodal treatment for men with locally advanced prostate cancer (PCa) using neoadjuvant/adjuvant systemic therapy, surgery, and radiation therapy is being increasingly explored. There is also interest in the oncologic benefit of treating the primary tumor in the setting of metastatic PCa (mPCa). To perform a review of the literature regarding the treatment of the primary tumor in the setting of mPCa. Medline, PubMed, and Scopus electronic databases were queried for English language articles from January 1990 to September 2014. Prospective and retrospective studies were included. There is no published randomized controlled trial (RCT) comparing local therapy and systemic therapy to systemic therapy alone in the treatment of mPCa. Prospective studies of men with locally advanced PCa and retrospective studies of occult node-positive PCa have consistently shown the addition of local therapy to a multimodal treatment regimen improves outcomes. Molecular and genomic evidence further suggests the primary tumor may have an active role in mPCa. Treatment of the primary tumor in mPCa is being increasingly explored. While preclinical, translational, and retrospective evidence supports local therapy in advanced disease, further prospective studies are under way to evaluate this multimodal approach and identify the patients most likely to benefit from the inclusion of local therapy in the setting of metastatic disease. In this review we explored preclinical and clinical evidence for treatment of the primary tumor in metastatic prostate cancer (mPCa). We found evidence to support clinical trials investigating mPCa therapy that includes local treatment of the primary tumor. Currently, treating the primary tumor in mPCa is controversial and lacks high-level evidence sufficient for routine recommendation.

Prostate cancer (PCa) patients found to have adverse pathologic features following radical prostatectomy (RP) are less likely to be cured with surgery alone.To analyze the role of postoperative radiotherapy (RT) in patients with aggressive PCa.We performed a systematic literature review of the Medline and EMBASE databases. The search strategy included the terms radical prostatectomy, adjuvant radiotherapy, and salvage radiotherapy, alone or in combination. We limited our search to studies published between January 2009 and August 2016.Three randomized trials demonstrated that immediate RT after RP reduces the risk of recurrence in patients with aggressive PCa. However, immediate postoperative RT is associated with an increased risk of acute and late side effects ranging from 15% to 35% and 2% to 8%, respectively. Retrospective studies support the oncologic efficacy of initial observation followed by salvage RT administered at the first sign of recurrence; however, the impact of this delay on long-term control remains uncertain. Hopefully, ongoing randomized trials will shed light on the role of adjuvant RT versus observation±salvage RT in individuals with adverse features at RP. Accurate patient selection based on clinical characteristics and molecular profile is crucial. Dose escalation, whole-pelvis RT, novel techniques, and the use of hormonal therapy might improve the outcomes of postoperative RT.Immediate RT reduces the risk of recurrence after RP in patients with aggressive disease. However, this approach is associated with an increase in the incidence of short- and long-term side effects. Observation followed by salvage RT administered at the first sign of recurrence might be associated with durable cancer control, but prospective randomized comparison with adjuvant RT is still awaited. Dose escalation, refinements in the technique, and the concomitant use of hormonal therapies might improve outcomes of patients undergoing postoperative RT.Postoperative radiotherapy has an impact on oncologic outcomes in patients with aggressive disease characteristics. Salvage radiotherapy administered at the first sign of recurrence might be associated with durable cancer control in selected patients but might compromise cure in others.

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.

Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown.To investigate long-term oncological outcomes after sLND in a large multi-institutional series.The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga prostate-specific membrane antigen ligand.The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND.At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa.A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND.We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.

To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the 'Title' and 'Abstract' fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta-analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3-7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence.

<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.

Pelvic lymph node dissection represents the gold standard of lymph node staging in patients with prostate cancer. We sought to assess the effect of extended pelvic lymph node dissection on oncologic outcomes in patients with characteristics of D'Amico intermediate or high risk prostate cancer treated with radical prostatectomy.In a multi-institutional database of 4 centers we identified 9,742 patients who underwent radical prostatectomy from 2000 to 2017 with or without pelvic lymph node dissection. Only patients with a greater than 5% probability of lymph node invasion according to the Briganti nomogram were included in study. We performed 2:1 propensity score matching to account for potential differences between the 2 cohorts. Cox regression models were used to test the effect of pelvic lymph node dissection on biochemical recurrence, metastasis and cancer specific mortality.Overall 707 patients (7.3%) did not undergo pelvic lymph node dissection, of whom 520 and 187 harbored D'Amico intermediate and high risk characteristics, respectively. A median of 14 lymph nodes (IQR 8-21) were removed in the pelvic lymph node dissection cohort and 1,714 of these cases (19.0%) harbored lymph node metastasis. After propensity score matching the biochemical recurrence-free, metastasis-free and cancer specific mortality-free survival rates were 60.4% vs 65.6% (p=0.07), 87.0% vs 90.0% (p=0.06) and 95.2% vs 96.4% (p=0.2) for pelvic lymph node dissection vs no pelvic lymph node dissection 120 months after radical prostatectomy. Multivariable Cox regression models adjusted for postoperative and preoperative tumor characteristics revealed that pelvic lymph node dissection performed at radical prostatectomy was no independent predictor of biochemical recurrence, metastasis or cancer specific mortality (all p ≥0.1).There was no significant difference in oncologic outcomes in patients with D'Amico high or intermediate risk prostate cancer in whom pelvic lymph node dissection was or was not performed at radical prostatectomy. The therapeutic value of pelvic lymph node dissection remains unclear.

Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes.To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs).First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification.The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone.In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint.We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

It is unknown whether specific locations of visceral metastatic sites affect overall survival (OS) of metastatic prostate cancer (mPCa) patients. We tested the association between specific locations of visceral metastatic sites and OS in mPCa patients.Within Surveillance, Epidemiology and End Results database (2010-2016), survival analyses relied on specific locations of visceral metastases: lung only vs. liver only vs. brain only vs. ≥2 visceral sites. Kaplan-Meier plots and Cox regression models were fitted.Of 1827 patients, 1044 (57%) harbored lung only visceral metastases vs. 457 (25%) liver only vs. 131 (7%) brain only vs. 195 (11%) ≥2 visceral sites. Median OS was 22 months in all patients vs. 33 months in lung only vs. 15 months in liver only vs. 16 months in brain only vs. 15 months in patients with ≥2 visceral sites. Highest OS was recorded in lung only visceral metastases patients, especially when concomitant nonvisceral metastases were located in lymph nodes only (median OS 57 months) vs. bone only (26 months) vs. lymph nodes and bone (28 months). Liver only, brain only or ≥2 visceral sites exhibited poor OS, regardless of concomitant nonvisceral metastases type (median OS from 13 to 19 months).In mPCa patients, lung only visceral metastases, especially when associated with lymph node only nonvisceral metastases, portend the best prognosis. Conversely, visceral metastatic sites other than lung portend poor prognosis, regardless of concomitant nonvisceral metastases type.

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. Link, Google Scholar 5 : Incidence of positive surgical margins after biopsy-selected nerve-sparing radical prostatectomy. Urology1998; 51: 437. Google Scholar 6 : Update on the appropriate staging evaluation for newly diagnosed prostate cancer. J Urol1997; 158: 687. Google Scholar 7 : The role of perineural space invasion in the local spread of prostatic adenocarcinoma. J Urol1989; 142: 763. Link, Google Scholar 8 : Positive surgical margins with radical prostatectomy: detailed pathological analysis and prognosis. Urology1996; 48: 80. Google Scholar 9 : Radical prostatectomy for impalpable prostate cancer: the Johns Hopkins experience with tumors found on transurethral resection (stages T1A and T1B) and on needle biopsy (stage T1C). J Urol1994; 152: 1721. Abstract, Google Scholar 10 : Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens. J Urol1992; 148: 331. Link, Google Scholar 11 : Evaluation of radical prostatectomy specimens: a comparative analysis of sampling methods. Am J Surg Pathol1992; 16: 315. Google Scholar 12 : Capsular penetration in prostate cancer, significance for natural history and treatment. Am J Surg Pathol1990; 14: 240. Google Scholar 13 : Analysis of risk factors associated with prostate cancer extension to the surgical margin and pelvic node metastasis at radical prostatectomy. J Urol1993; 150: 1845. Link, Google Scholar 14 : Positive surgical margins with radical prostatectomy: detailed pathological analysis and prognosis. Urology1996; 48: 80. Google Scholar 15 : Positive surgical margins at radical prostatectomy: importance of the apical dissection. J Urol1990; 143: 1166. Link, Google Scholar 16 : Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol1996; 20: 286. Crossref, Medline, Google Scholar 17 : A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. J Urol1995; 154: 131. Google Scholar 18 : Positive margins after radical prostatectomy: correlation with local recurrence and distant progression. Br J Urol1993; 72: 489. Google Scholar 19 : Combination of prostate specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer: a multi-institutional update. JAMA1997; 277: 1445. Google Scholar 20 : Evaluation of a nomogram for predicting pathologic stage of men with clinically localized prostate cancer. Cancer1997; 79: 528. Google Scholar 21 : Systematic biopsies and digital rectal examination to identify the nerve-sparing side for radical prostatectomy without risk of positive margin in patients with clinical stage T2, N0 prostatic carcinoma. Urology1994; 44: 211. Google Scholar 22 : Histologic grading and staging of prostatic carcinoma. In: Urologic Pathology: The Prostate. Edited by . Philadelphia: Lea & Febiger1977: 171. Google Scholar 23 TNM Atlas. New York: Springer-Verlag1997: 272. Google Scholar 24 : Morphologische Grundlagen zur radikalen Prostatektomie. Urologe A1991; 30: 361. Google Scholar 25 : Zonal distribution of prostatic adenocarcinoma. Correlation with histologig pattern and direction of spread. Am J Pathol1988; 12: 897. Google Scholar 26 : Classification and regression tree used for the exploration of prognostic factors measured on different scales. In: Computational Statistics. Edited by . Heidelberg: Physika Verlag1994: 484. Google Scholar 27 : Preoperative prediction of organ-confined (pT2) tumor growth to indicate a bilateral nerve-sparing radical prostatectomy (NSRP). J Urol1999; 161: 208. abstract 925. Google Scholar 28 : Accuracy of prostate needle biopsy in predicting extracapsular tumor extension at radical prostatectomy: application in selecting patients for nerve-sparing surgery. Urology1998; 52: 814. Google Scholar 29 : The percent of cores positive for cancer in prostate needle biopsy specimens is strongly predictive of tumor stage and volume at radical prostatectomy. J Urol2000; 163: 174. Link, Google Scholar 30 : Improved predictibility of extracapsular extension and seminal vesical involvement based on clinical and biopsy findings in prostate cancer in Japanese men. Urology1998; 52: 433. Google Scholar 31 : Use of systematic biopsy results to predict pathologic stage in patients with clinically localized prostate cancer: a preliminary report. Int J Urol1998; 5: 337. Crossref, Medline, Google Scholar 32 : Ability of sextant biopsies to predict radical prostatectomy stage. Urology1998; 51: 759. Google Scholar 33 : Preoperative predictors for organ-confined disease in Japanese patients with stage T1c prostate cancer. Int J Urol1998; 5: 454. Google Scholar 34 : Early PSA relapse after radical retropubic prostatectomy: prediction on the basis of preoperative and postoperative tumor characteristics. Eur Urol1999; 36: 21. Google Scholar 35 : Systematic sextant biopsies enhance the accuracy of predicting pelvic lymph node metastasis in prostatic cancer. J Urol1998; 159: 2023. Link, Google Scholar 36 : Biological determinants of cancer progression in men with prostate cancer. JAMA1999; 281: 1395. Crossref, Medline, Google Scholar 37 : A novel strategy for selecting patients for nerve-sparing radical prostatectomy. J Urol2000; 163: 288. abstract 1279. Google Scholar 38 : Stage migration in clinically localized prostate cancer. Eur Urol2000; 38: 74. Google Scholar 39 : Potenz und Kontinenz nach radikaler Prostatektomie. Onkologe2000; 6: 123. Google Scholar 40 : Functional evaluation of penile hemodynamics. J Urol1988; 139: 734. 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 ...