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Purpose: The impact of African-American race on oncologic outcomes for low risk prostate cancer is unclear due to conflicting data. We investigated the effect of African-American race on pathological upgrading and/or up staging at prostatectomy in men with clinically low risk prostate cancer., Materials and Methods: We queried the National Cancer Database for men with low risk prostate cancer (clinical stage T2a or less, Gleason score 6 or less, prostate specific antigen less than 10 ng/ml) treated with radical prostatectomy between 2010 and 2013. The outcomes were pathological upgrading to Gleason score greater than 6 (primary) or Gleason score greater than 3+4=7 (secondary) and/or up staging (pathological T3-4 or N1 disease). The association between race and the end points was assessed using multivariable logistic regression. To further adjust for potential confounders, stratification by urban residence and comorbidity score, and subgroup analyses were performed., Results: With adjustment for age, comorbidity, income, urban residence, T stage, prostate specific antigen and percentage of positive biopsy cores, African-American race conferred 1.2-fold higher odds of pathological upgrading to Gleason score greater than 6 and/or up staging (OR 1.2, 95% CI 1.1-1.3, p <0.01). African-American race also was an independent predictor of pathological upgrading to Gleason score greater than 3+4=7 and/or up staging (p=0.03)., Conclusions: African-American men with low risk prostate cancer are more likely to harbor higher risk disease, which may lead to adverse outcomes. This finding alone does not preclude active surveillance. However, race should be considered as men weigh the risks and benefits of active surveillance vs treatment., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, p<0.001). AA men were more likely to be m-SPINK1(+) (13% vs 7%; p=0.069) and triple-negative (50% vs 37%; p=0.043). Racial differences in molecular subtypes did not persist when tumors were analyzed by location, suggesting a biologically important relationship between tumor location and subtype. Accordingly, anterior tumor location was associated with higher Decipher scores and lower global AR signaling., Patient Summary: This study demonstrates associations among patient race, prostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships., (Copyright © 2015. Published by Elsevier B.V.)

Background: It remains unclear whether men selecting active surveillance (AS) are at increased risk of unfavorable longer term outcomes as compared with men who undergo immediate treatment., Objective: To compare adverse pathologic outcomes in men with favorable-risk prostate cancer who underwent delayed prostatectomy after surveillance (DPAS) to those who elected immediate prostatectomy (IRP)., Design, Setting, and Participants: We conducted a retrospective analysis of a prospective AS registry from 2004 to 2014. From the Johns Hopkins AS program (n = 1298), we identified a subset of men who underwent DPAS (n = 89) and was representative of the entire cohort, not just those that were reclassified to higher risk. These men were compared with men who underwent IRP (n = 3788)., Outcome Measurements and Statistical Analysis: We measured adverse pathologic features (primary Gleason pattern ≥ 4, seminal vesicle invasion [SVI], or lymph node [LN] positivity). Multivariable models were adjusted for age, prostate-specific antigen density, and baseline risk classification., Results and Limitations: Delayed prostatectomy occurred at a median of 2.0 yr (range: 0.6-9.0) after diagnosis. The DPAS and IRP cohorts demonstrated similar proportions of men with primary Gleason pattern ≥ 4 (17% vs 20%; p = 0.11), SVI (3.3% vs 3.2%; p = 0.53), LN positivity (2.3% vs 1.2%; p = 0.37), and overall adverse pathologic features (21.3% vs 17.0%; p = 0.32). The adjusted odds ratio of adverse pathology was 1.33 (95% confidence interval, 0.82-2.79; p = 0.13) for DPAS as compared with IRP. Limitations include a modest cohort size and a limited number of events., Conclusions: In men with favorable-risk cancer, the decision to undergo AS is not independently associated with adverse pathologic outcomes., Patient Summary: This report compares men with favorable-risk prostate cancer who elected active surveillance with those who underwent immediate surgery accounting for evidence that approximately one-third of men who choose surveillance will eventually undergo treatment. Our findings suggest that men who are closely followed with surveillance may have similar outcomes to men who elect immediate surgery, but additional research is needed., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Current guidelines suggest adjuvant radiation therapy for men with adverse pathologic features (APFs) at radical prostatectomy (RP). We examine at-risk men treated only with RP until the time of metastasis., Objective: To evaluate whether clinicopathologic risk models can help guide postoperative therapeutic decision making., Design, Setting, and Participants: Men with National Comprehensive Cancer Network intermediate- or high-risk localized prostate cancer undergoing RP in the prostate-specific antigen (PSA) era were identified (n=3089). Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis were included. APFs were defined as pT3 disease or positive surgical margins., Outcome Measurements and Statistical Analysis: Area under the receiver operating characteristic curve (AUC) for time to event data was used to measure the discrimination performance of the risk factors. Cumulative incidence curves were constructed using Fine and Gray competing risks analysis to estimate the risk of biochemical recurrence (BCR) or metastasis, taking censoring and death due to other causes into consideration., Results and Limitations: Overall, 43% of the cohort (n=1327) had APFs at RP. Median follow-up for censored patients was 5 yr. Cumulative incidence of metastasis was 6% at 10 yr after RP for all patients. Cumulative incidence of metastasis among men with APFs was 7.5% at 10 yr after RP. Among men with BCR, the incidence of metastasis was 38% 5 yr after BCR. At 10 yr after RP, time-dependent AUC for predicting metastasis by Cancer of the Prostate Risk Assessment Postsurgical or Eggener risk models was 0.81 (95% confidence interval [CI], 0.72-0.97) and 0.78 (95% CI, 0.67-0.97) in the APF population, respectively. At 5 yr after BCR, these values were lower (0.58 [95% CI, 0.50-0.66] and 0.70 [95% CI, 0.63-0.76]) among those who developed BCR. Use of risk model cut points could substantially reduce overtreatment while minimally increasing undertreatment (ie, use of an Eggener cut point of 2.5% for treatment of men with APFs would spare 46% from treatment while only allowing for metastatic events in 1% at 10 yr after RP)., Conclusions: Use of risk models reduces overtreatment and should be a routine part of patient counseling when considering adjuvant therapy. Risk model performance is significantly reduced among men with BCR., Patient Summary: Use of current risk models can help guide decision making regarding therapy after surgery and reduce overtreatment., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Prostate cancers incite tremendous morbidity upon metastatic growth. We previously identified Asporin (ASPN) as a potential mediator of metastatic progression found within the tumor microenvironment. ASPN contains an aspartic acid (D)-repeat domain and germline polymorphisms in D-repeat-length have been associated with degenerative diseases. Associations of germline ASPN D polymorphisms with risk of prostate cancer progression to metastatic disease have not been assessed., Experimental Design: Germline ASPN D-repeat-length was retrospectively analyzed in 1,600 men who underwent radical prostatectomy for clinically localized prostate cancer and in 548 noncancer controls. Multivariable Cox proportional hazards models were used to test the associations of ASPN variations with risk of subsequent oncologic outcomes, including metastasis. Orthotopic xenografts were used to establish allele- and stroma-specific roles for ASPN D variants in metastatic prostate cancer., Results: Variation at the ASPN D locus was differentially associated with poorer oncologic outcomes. ASPN D14 [HR, 1.72; 95% confidence interval (CI), 1.05-2.81, P = 0.032] and heterozygosity for ASPN D13/14 (HR, 1.86; 95% CI, 1.03-3.35, P = 0.040) were significantly associated with metastatic recurrence, while homozygosity for the ASPN D13 variant was significantly associated with a reduced risk of metastatic recurrence (HR, 0.44; 95% CI, 0.21-0.94, P = 0.035) in multivariable analyses. Orthotopic xenografts established biologic roles for ASPN D14 and ASPN D13 variants in metastatic prostate cancer progression that were consistent with patient-based data., Conclusions: We observed associations between ASPN D variants and oncologic outcomes, including metastasis. Our data suggest that ASPN expressed in the tumor microenvironment is a heritable modulator of metastatic progression., (©2015 American Association for Cancer Research.)

Background: The objective of this study was to evaluate the use of neoadjuvant chemoradiation in patients with prostate sarcoma treated at our institution and report oncological outcomes., Materials and Methods: The records of patients with intermediate- or high-grade prostate sarcoma treated with curative intent at our institution from 1993 to 2013 were reviewed. Patient demographic information, tumor characteristics, and treatment modalities used were assessed. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were calculated., Results: Eight patients met inclusion criteria. The mean age at presentation was 64 years, and urinary obstruction was the most common presenting symptom. All patients underwent surgical resection and neoadjuvant radiation and 6 had concurrent chemotherapy. Four patients received intraoperative radiation. With a median follow-up of 36 months, there were no local recurrences, 6 metastases, 4 deaths from disease, and no deaths from other causes. The median OS and CSS was 67.8 months, with actuarial OS and CSS rates of 100% at 1 year, 75% at 2 years, 62.5% at 3 years, and 62.5% at 5 years. Median RFS was 14.2 months, with actuarial RFS rate of 75% at 1 year, 37.5% at 2 years, and 25% at 3 years., Conclusion: Prostate sarcomas are rarely cured using surgical resection alone. Our cohort treated with a multimodality approach had favorable CSS and RFS compared with historic and contemporary series of surgery alone and no local recurrences. Most patients developed metastatic recurrence, highlighting the aggressive nature of this disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting., Methods: In 2008-2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patient's eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation., Results: Overall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam radiotherapy ± androgen deprivation (39.3%), radical prostatectomy (32.0%), and active surveillance/expectant management (12.9%)., Conclusions: A once-weekly same-day evaluation that involves simultaneous data evaluation, management discussion, and patient consultations from a multidisciplinary team of PCa specialists is feasible. Comprehensive evaluation at a tertiary referral center, as demonstrated in a modern MDC setting, is associated with critical changes in presenting disease classification in over one in four men., (© 2014 Wiley Periodicals, Inc.)

Objective: To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry., Methods: The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage ≤T1, Gleason score ≤6, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm(3), positive cores <3, percent cancer per core ≤50), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions., Results: AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume., Conclusion: AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians. Therefore, if the goal of AS is to selectively monitor men with low-grade disease, AA men may require alternate selection criteria., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To report race-based outcomes after radical prostatectomy (RP) in a cohort stratified by National Comprehensive Cancer Network (NCCN) risk category with updated follow-up., Materials and Methods: Studies describing racial disparities in outcomes after RP are conflicting. We studied 15,993 white and 1634 African American (AA) pretreatment-naïve men who underwent RP at our institution (1992-2013) with complete preoperative and pathologic data. Pathologic outcomes were compared between races using appropriate statistical tests; biochemical recurrence (BCR) for men with complete follow-up was compared using multivariate models that controlled separately for preoperative and postoperative covariates., Results: Very low- and low-risk AA men were more likely to have positive surgical margins (P <.01), adverse pathologic features (P <.01), and be upgraded at RP (P <.01). With a median follow-up of 4.0 years after RP, AA race was an independent predictor of BCR among NCCN low-risk (HR, 2.16; P <.001) and intermediate-risk (hazard ratio [HR], 1.34; P = .024) classes and pathologic Gleason score ≤ 6 (HR, 2.42; P <.001) and Gleason score 7 (HR, 1.71; P <.001). BCR-free survival for very low-risk AA men was similar to low-risk white men (P = .890); BCR-free survival for low-risk AA men was similar to intermediate-risk white men (P = .060)., Conclusion: When stratified by NCCN risk, AA men with very low-, low-, or intermediate-risk prostate cancer who undergo RP are more likely to have adverse pathologic findings and BCR compared with white men. AA men with "low risk" prostate cancer, especially those considering active surveillance, should be counseled that their recurrence risks can resemble those of whites in higher risk categories., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a)., Patients and Methods: PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery., Results: Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%)., Conclusions: Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases., (© 2014 The Authors. BJU International © 2014 BJU International.)

Background: Men destined to have early biochemical recurrence (BCR) following radical prostatectomy (RP) may be optimal candidates for multimodal treatment. Here we identified pre-operative predictors of early BCR within a surgical cohort who recurred., Methods: An institutional prostate cancer (PCa) database containing over 20,000 patients was queried to identify 1,471 men who had BCR after RP, and pre-operative predictors of early versus late BCR were assessed. Early BCR was defined as recurrence within 1 year after RP. Within the recurrence cohort, those with National Comprehensive Cancer Network (NCCN) high-risk features were more likely to experience early BCR. Therefore, in all NCCN high-risk men in the database, we abstracted detailed pathologic biopsy data. Among 753 high-risk men, 41 alternate multivariable criteria were assessed for their ability to predict early BCR in crude and adjusted logistic regression models., Results: The criteria that best identified those likely to experience early BCR are primary Gleason pattern 5 on biopsy or ≥4 cores containing pattern 4 (odds ratio 3.17, P < 0.001). These criteria included 26.7% of NCCN high-risk men. Additionally, these criteria selected for men within the high-risk classification who were at significantly higher risk of subsequent metastasis (adjusted hazard ratio 3.04, P < 0.001) and cancer-specific death (adjusted hazard ratio 3.27, P < 0.001)., Conclusions: In men with PCa who present with high-risk features, pre-operative criteria have the ability to discriminate the subgroup most likely to experience early BCR after RP. Men at risk for early disease recurrence may be the most suitable candidates for multimodal therapy., (© 2014 Wiley Periodicals, Inc.)

Purpose: Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences., Materials and Methods: Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade., Results: Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm(3) (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm(3), p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001)., Conclusions: Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Pelvic lymph node dissection (PLND) is a standard component of radical cystectomy (RC) for bladder cancer. The optimal anatomic PLND template remains undefined. An extended PLND template can potentially improve survival through the eradication of micrometastatic disease and improved pathologic staging. However, this benefit could be compromised by a potential increase in perioperative complications and cost. Two randomized controlled clinical trials that will clarify this question are ongoing. Many important retrospective studies have provided insights into the optimal PLND extent. Here the authors review the key evidence that informs how urologists may tailor the PLND template during RC depending on patient and tumor characteristics.

Objective: To evaluate the operative and pathologic outcomes of laparoscopic radical prostatectomy and robot-assisted radical prostatectomy in men with progressive changes in body mass index (BMI) category., Materials and Methods: A single-surgeon series of 1023 laparoscopic radical prostatectomy and robot-assisted radical prostatectomy (mostly extraperitoneal) patients was considered. Of these patients, 987 were evaluable. Results were stratified by the World Health Organization BMI category. Multivariate linear and logistic regression analysis was used to model the operating time, length of stay, positive surgical margins, and noncurable cancer., Results: Of the 987 patients, 563 (57%) were overweight and 193 (19.6%) were obese. Of the 193 obese patients, 152 (15.4%) had a BMI of 30 to <35 kg/m(2) (class I obesity), 28 (2.8%) a BMI of 35 to <40 kg/m(2) (class II), and 13 (1.3%) a BMI of ≥40 kg/m(2) (class III). No differences were found in the estimated blood loss, complications, PSM, pathologic stage, or biochemical recurrence across the BMI categories (6-month median follow-up). However, pelvic lymph node dissection was more commonly omitted and the nerve-sparing score was inferior in the obese men. On multivariate analysis, a higher BMI was a significant predictor of a longer operating time., Conclusion: Obese men can safely undergo laparoscopic radical prostatectomy or robot-assisted radical prostatectomy, although the ability to perform excellent nerve sparing appears to decrease with increasing obesity. Nevertheless, obese men can expect perioperative and early oncologic outcomes comparable to those of normal weight men without an increased risk of perioperative complications., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Active surveillance (AS) is a treatment option for men with very low-risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low-risk PCa, we evaluated oncologic outcomes of AA men with very low-risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP)., Patients and Methods: We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low-risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features., Results: AA men with very low-risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03)., Conclusion: AA men with very low-risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low-risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.

Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation, and combined modality treatment. Specific outcomes of radical prostatectomy and combined modality treatment for high-risk prostate cancer are reviewed. The rationale for extended pelvic lymphadenectomy at the time of surgery is discussed, as is the role for surgery in the setting of node-positive, high-risk disease. There is not yet a biomarker that accurately identifies lethal prostate cancer, but rigorous clinical studies have identified methods of optimizing oncologic outcomes in high-risk men.

Objective: Patients diagnosed with upper tract urothelial carcinoma (UTUC) sometimes experience a delay from diagnosis to extirpative surgery (nephroureterectomy or ureterectomy) as a result of attempted endoscopic management and/or neoadjuvant chemotherapy. The purpose of this analysis is to examine the impact of such delay on survival outcomes., Methods: An IRB-approved retrospective review identified consecutive patients undergoing extirpative surgery for UTUC treated at a single institution between 1990 and 2007. 240 patients with non-metastatic disease represented both primarily-presenting and referred patients. Patients in the "early" surgery group underwent extirpative surgery <3 months after diagnosis and patients in the "delayed" surgery group underwent surgery ≥ 3 months after diagnosis. Timing to surgery was at the discretion of individual patient-surgeon decision-making. Analyses and measurements were univariate and multivariate models correlating death from disease with clinico-pathologic parameters, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in the "early" and "delayed" surgery groups., Results: 186 patients underwent early surgery and 54 patients underwent delayed surgery. Median follow-up for all patients was 29 months. The 5-year CSS were 72% and 71% for the early versus late groups, respectively (P = 0.39) and corresponding 5-year OS rates were 60% and 69%, respectively (P = 0.69). Delay in surgery was not associated with a worse outcome, even following adjustment for potential confounders. The most common factor contributing to delayed surgery in our cohort was administration of neoadjuvant chemotherapy (50%), which did not impact survival. Limitations included a median follow-up of 19 months in the neoadjuvant group; and the requirement to analytically group pathologic high-stage and low-stage disease, which reflects challenges inherent to current clinical staging., Conclusions: Our results show no difference in survival between patients undergoing early versus delayed extirpative surgery for UTUC, suggesting the feasibility of delayed surgery in appropriately selected patients. Only prospective validation of delayed surgery can guarantee its safety., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: inhibitors of apoptosis proteins (IAPs) have been shown to contribute to resistance of neoplastic cells to chemotherapy and to biologic antineoplastic agents. Consequently, new agents are being developed targeting this family of proteins. In a panel of bladder cancer cell lines, we evaluated a Smac mimetic that antagonizes several IAPs for its suitability for bladder cancer therapy. Experimental design: A panel of seven bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic compound-A alone, TRAIL alone, chemotherapy alone, compound-A plus TRAIL, and compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and caspase activation were examined by western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and western blotting. Finally, siRNA knockdown of XIAP was correlated with the sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA fragmentation and western blotting., Results: single-agent compound-A had little effect, but compound-A augmented TRAIL- and chemotherapy-induced apoptosis. Immunoblotting showed that combination treatment with compound-A and TRAIL resulted in cleavage of procaspase-3 and procaspase-7, activation of which irreversibly commits cells to apoptosis. Immunoprecipitation of XIAP showed displacement of active caspase-3 fragments from XIAP, supporting the proposed mechanism of action. Furthermore, siRNA-mediated silencing of XIAP similarly sensitized these cells to apoptosis., Experimental Design: a panel of seven bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic compound-Alone, TRAIL alone, Chemotherapy alone, compound-A plus TRAIL and compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and caspase activation were examined by western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and western blotting. Finally siRNA knockdown of XIAP was correlated with the sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA fragmentation and western blotting., Conclusion: our results suggest that targeting of XIAP with the Smac mimetic compound-A has the potential to augment the effects of a variety of chemotherapeutic and biologic therapies in bladder cancer.

Background: Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients., Methods: Between 1980 and 2003, 97 patients with metastatic nonseminomatous germ cell tumor and pure teratoma histology at the time of PC-RPLND were identified. The medical records of these patients were reviewed retrospectively for pertinent clinical and treatment-related outcomes., Results: At a median follow-up of 7.4 years, 21 patients (22%) developed recurrent disease after PC-RPLND. The 5-year and 10-year probabilities (+/-standard error) of freedom from disease recurrence were 81%+/-4% and 76%+/-5%, respectively. The postchemotherapy alpha-fetoprotein (AFP) level and mediastinal involvement at presentation were statistically significant predictors of disease recurrence on multivariate analysis. Nine of 97 patients (9.3%) died from testis cancer, and 4 patients died from other causes., Conclusions: In patients with pure teratoma histology at PC-RPLND, mediastinal involvement at presentation and the presence of an elevated AFP level before PC-RPLND predicted an unfavorable outcome. The absence of mediastinal involvement and normal AFP level, however, did not confirm freedom from disease recurrence. Patients who had teratoma at the time of PC-RPLND remained at considerable risk for disease progression because of the unpredictable nature of teratoma and the presence of unrecognized, active germ cell disease outside the retroperitoneum., (Copyright (c) 2009 American Cancer Society.)