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Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.

Background: The potential harms of a prostate cancer (PCa) diagnosis may outweigh its benefits in elderly men., Objective: To assess the use of prostate biopsy in men with limited life expectancy (LE) within the practices comprising the Michigan Urological Surgery Improvement Collaborative (MUSIC)., Design, Setting, and Participants: MUSIC is a consortium of 42 practices and nearly 85% of the urologists in Michigan. From July 2013 to October 2014, clinical data were collected prospectively for all men undergoing prostate biopsy., Outcome Measurements and Statistical Analysis: We calculated comorbidity-adjusted LE in men aged ≥66 yr and identified men with <10 yr LE (limited LE) undergoing a first biopsy. Our LE calculator was not designed for men aged <66 yr; thus these men were excluded. Multivariable models estimated the proportion of all biopsies performed for men with limited LE in each MUSIC practice, adjusting for differences in patient characteristics. We also evaluated what treatments, if any, these patients received., Results and Limitations: Among 3035 men aged ≥66 yr undergoing initial prostate biopsy, 60% had none of the measured comorbidities. Overall, 547 men (18%) had limited LE. Compared with men with a longer LE, these men had significantly higher prostate-specific antigen levels and abnormal digital rectal examination findings. The adjusted proportion of biopsies performed for men with limited LE ranged from 3.8% to 39% across MUSIC practices (p < 0.001). PCa was diagnosed in 69% of men with limited LE; among this group, 74% received any active treatment. Of these men, 46% had high-grade cancer (Gleason score 8-10)., Conclusions: Among a large and diverse group of urology practices, nearly 20% of prostate biopsies are performed in men with limited LE. These data provide useful context for quality improvement efforts aimed at optimizing patient selection for prostate biopsy., Patient Summary: In this report, nearly 2 of every 10 men undergoing prostate biopsy had a life expectancy (LE) <10 yr. Implementing LE calculators in clinical practice may help refine patient selection for prostate biopsy., (Published by Elsevier B.V.)

The International Society of Urological Pathology in 2010 recommended weighing prostates without seminal vesicles (SV) to include only prostate weight in prostate-specific antigen (PSA) density (PSAD) calculation, because SV do not produce PSA. Large retrospective cohorts exist with combined weight recorded that needs to be modified for retrospective analysis. Weights of prostates and SV were separately recorded in 172 consecutive prostatectomies. The average weight of SV and proportion of prostate weight from combined weight were calculated. The adjustment factors were then validated on databases of 2 other institutions. The average weight of bilateral SV was 6.4 g (range = 1-17.3 g). The prostate constituted on average 87% (range = 66% to 98%) of the total specimen weight. There was no correlation between patient age and prostate weight with SV weight. The best performing correction method was to subtract 6.4 g from total radical prostatectomy weight and to use this weight for PSAD calculation. The average weights of retrospective specimens weighed with SV were not significantly different between the 3 institutions. Using our data allowed calibration of the weights and PSAD between the cohorts weighed with and without SV. Thus, prostate weight in specimens including SV weight can be adjusted by subtracting 6.4 g, resulting in significant change of PSAD. Some institution-specific variations may exist, which could further increase the precision of retrospective analysis involving prostate weight and PSAD. However, unless institution-specific adjustment parameters are developed, we recommend that this correction factor be used for retrospective cohorts or in institutions where combined weight is still recorded., (© The Author(s) 2015.)

Objective: To identify which high-risk patients with prostate cancer may harbour favourable pathological outcomes at radical prostatectomy (RP)., Patients and Methods: We evaluated 810 patients with high-risk prostate cancer, defined as having one or more of the following: PSA level of >20 ng/mL, Gleason score ≥8, clinical stage ≥T2c. Patients underwent robot-assisted RP (RARP) with pelvic lymph node dissection, between 2003 and 2012, in one centre. Only 1.6% (13/810) of patients received any adjuvant treatment. Favourable pathological outcome was defined as specimen-confined disease (SCD; pT2-T3a, node negative, and negative surgical margins) at RARP-specimen. Logistic regression models were used to test the relationship among all available predicators and harbouring SCD. A logistic regression coefficient-based nomogram was constructed and internally validated using 200 bootstrap resamples. Kaplan-Meier method estimated biochemical recurrence (BCR)-free and cancer-specific mortality (CSM)-free survival rates, after stratification according to pathological disease status., Results: Overall, 55.2% patients harboured SCD at RARP. At multivariable analysis, PSA level, clinical stage, primary/secondary Gleason scores, and maximum percentage tumour quartiles were all independent predictors of SCD (all P < 0.04). A nomogram based on these variables showed 76% discrimination accuracy in predicting SCD, and very favourable calibration characteristics. Patients with SCD had significantly higher 8-year BCR- (72.7% vs 31.7%, P < 0.001) and CSM-free survival rates (100% vs 86.9%, P < 0.001) than patients with non-SCD., Conclusions: We developed a novel nomogram predicting SCD at RARP. Patients with SCD achieved favourable long-term BCR- and CSM-free survival rates after RARP. The nomogram may be used to support clinical decision-making, and aid in selection of patients with high-risk prostate cancer most likely to benefit from RARP., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Reports on long-term oncologic outcomes for patients who undergo robot-assisted radical prostatectomy (RARP) are scant, as for radical prostatectomy covering only the contemporary prostate-specific antigen (PSA) era., Objective: To evaluate cancer control in men who underwent RARP at least 10 yr ago., Design, Setting, and Participants: From 2001 to 2003, we followed 483 consecutive men with localized prostate cancer who underwent RARP at a high-volume tertiary center., Intervention: RARP as first-line therapy., Outcome Measurements and Statistical Analysis: We calculated biochemical recurrence -free survival (BCRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS). Actuarial rates were estimated via Kaplan-Meier. Cox proportional hazards models were used to identify variables predictive of biochemical recurrence (BCR), receipt of salvage therapy, and metastases., Results and Limitations: There were 108 patients with BCR at a median follow-up of 121 mo (interquartile range: 97-132). Actuarial BCRFS, MFS, and CSS rates at 10 yr were 73.1%, 97.5%, and 98.8%, respectively. On multivariable analysis, D'Amico risk groups or pathologic Gleason grade, stage, and margins were the strongest predictors of BCR depending on whether preoperative or postoperative variables were considered. The value of the detectable PSAs together with disease severity were independent predictors of receipt of salvage therapy, together with a persistent PSA for metastases., Conclusions: In contemporary patients with localized prostate cancer, RARP confers effective 10-yr cancer control. Disease severity and PSA measurements can be used to guide more personalized and cost-effective postoperative surveillance regimens., Patient Summary: Robot-assisted radical prostatectomy confers effective 10-yr cancer control for men with localized disease, similar to the open approach. Recurrence is best predicted by postoperative disease severity. Persistent disease signals the risk of progression likely requiring early salvage treatment; lower postoperative risk warrants protracted surveillance beyond 5 yr from surgery, and those with higher risk may require follow-up beyond 10 yr., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: The implications of positive surgical margin (PSM) extent and location during radical perineal prostatectomy (RPP) have not been assessed in a contemporary series. We aimed to examine the incidence, location, and extent of PSM as well as their impact on biochemical recurrence (BCR) following RPP., Materials and Methods: A total of 794 patients underwent RPP by a single surgeon between June 1993 and August 2010. Covariates included age, pathologic T stage, pathologic Gleason sum, preoperative PSA, prostate volume, PSM extent, and location. Life table, Kaplan-Meier, and Cox regression analyses assessed predictors of BCR following RPP., Results: PSM were recorded in 162 patients (20.4%); of these, 83 (51.2%) were focal (≤ 1 mm) whereas 79 (48.8%) were broad (>1 mm). Location of PSM was anterior 10.5%, posterior or lateral 14.8%, bladder neck 23.5%, apical 32.1%, and multifocal 19.1%. At a median follow-up of 54 months, the 5-year BCR-free probability was 90.8% in patients with negative margins, 77.5% in patients with focal PSM, and 47.5% in patients with broad PSM. On multivariable analyses adjusted for age, pathologic T stage, pathologic Gleason sum, preoperative PSA, and prostate volume, broad PSM, (HR = 3.49, P < 0.001) as well as anterior (HR = 3.77, P = 0.003), bladder neck (HR = 2.25, P = 0.01) and multifocal (HR = 3.55, P < 0.001) PSM were independent predictors of BCR., Conclusions: In this study, we present oncologic outcomes following RPP in a large contemporary cohort of patients undergoing RPP. In adjusted analyses, broad and anterior PSM carried the highest risk of recurrence after RPP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Pathologic upgrading to Gleason 7 or higher on radical prostatectomy (RP) specimens occurs in many patients with Gleason 6 prostate cancer on preoperative biopsy. We evaluated whether biopsy characteristics and preoperative factors, including preoperative PSA velocity (PSAV), are predictive of pathologic upgrading., Materials and Methods: We identified 235 consecutive Gleason 6 prostate cancer patients who underwent biopsies at our institution, had multiple pre-biopsy PSA values, and eventually underwent RP. Preoperative biopsy, clinical characteristics, and PSAV were analyzed to determine the risk of pathologic upgrading or extracapsular extension. These clinical factors were evaluated for association with biochemical recurrence following RP., Results: Overall, 48% of patients were upgraded to Gleason grade 7 or higher following RP. Median PSAV was 0.61 ng/mL/y, and PSAV was similar between upgraded and non-upgraded patients (1.01 vs. 0.78, P = 0.1). PSA velocity level was not associated with extracapsular disease (P = 0.4). PSA velocity > 1 was associated with biochemical recurrence (HR 3.23, P = 0.01) but this was not statistically significant in a multivariable model. Increasing PSA density (HR 2.18, P < 0.001), bilateral cores positive (HR 1.89, P < 0.05), and any biopsy core involvement > 50% (HR 2.52, P < 0.05) were most associated with pathologic upgrading. On multivariate analysis, only bilateral cancer detection at biopsy (HR 1.90, P < 0.05) significantly predicted upgrading., Conclusions: PSAV has a limited role in predicting Gleason 6 upgrading. Patients with bilateral cancer detected on transrectal biopsy should be encouraged to have radical local therapy due to high risk of harboring more aggressive disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence-free survival (BCRFS) after robot-assisted radical prostatectomy (RARP)., Patients and Methods: Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan-Meier method and log-rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling., Results: The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow-up was 23 (10-46) months and 19 (7-37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS., Conclusions: Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high-grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours., (© 2010 HENRY FORD HOSPITAL HEALTH SYSTEM. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Introduction: To describe a technique that may facilitate neurovascular bundle preservation during robot-assisted radical prostatectomy., Materials and Methods: From December 2007 to January 2008, 10 patients underwent robot-assisted radical prostatectomy with bilateral nerve preservation. Hydrodissection of the neurovascular bundle was performed by injecting a 1:10000 epinephrine solution diluted in 0.9% normal saline into the lateral prostatic pedicle with an injection cannula needle (Wolf). Operative time, blood loss and margin status were assessed when this new technique was utilized. Erectile function status will be analyzed in the future., Results: Ten potent patients underwent bilateral nerve-sparing robot-assisted radical prostatectomy with hydrodissection. Mean patient age was 54 years old. Mean preoperative Gleason score was 6.5 and mean pretreatment PSA was 7.0. Six patients were clinical stage T1c and four patients were T2a. The mean operative time was 182 minutes, with a range of 148 minutes to 230 minutes. Mean blood loss was 297 cc. Hemodynamic changes were not seen during hydrodissection or after hydrodissection. No intraoperative or postoperative complications developed. None of the ten patients developed delayed postoperative bleeding. Final pathologic stage was pT2 in eight patients, pT3 in one patient and pT4 in one patient. All surgical margins were negative, except in the patient with bladder neck invasion., Conclusions: We describe an athermal technique which may facilitate neurovascular bundle preservation. While intraoperative parameters were favorable with hydrodissection, long term sexual function results need to be analyzed.

Prostate cancer remains the most commonly diagnosed noncutaneous malignancy in American men. Currently, there are 3 standard treatment options available to men with early prostate cancer: expectant management, radiation therapy, and radical prostatectomy. Although a number of studies have evaluated survival after treatment for early prostate cancer, the optimal choice of therapy for any given patient remains a difficult decision and requires the consideration of a variety of patient and tumor factors. The final selection of therapy for early prostate cancer should be based on an informed discussion between the physician and patient. To accomplish this goal, patients must be made familiar with the pertinent factors that affect survival. We review the factors most relevant for patients to understand as they consider their treatment options for early prostate cancer and summarize the data for physicians who counsel them., (Copyright 2002 by W.B. Saunders Company)