PTEN Loss with ERG Negative Status is Associated with Lethal Disease after Radical Prostatectomy.

PURPOSE: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. RESULTS: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). CONCLUSIONS: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.

The Genomic and Molecular Pathology of Prostate Cancer: Clinical Implications for Diagnosis, Prognosis, and Therapy.

Prostate cancer (PCa) is the most common noncutaneous malignancy affecting American men and the second most common cause of cancer death. The traditional risk classification schemes for PCa are limited due to the vast clinical and molecular heterogeneity of the disease. Fortunately, recent advancements in sequencing technologies have provided us with valuable insight into the genomics of PCa. To date, a wide array of recurrent genomic alterations in PCa have been identified. Incorporating these distinct molecular subtypes of PCa into prediction models provides opportunities for improved risk stratification and ultimately better patient outcomes. In this review, we summarize the key molecular subtypes of PCa and focus on those genomic alterations that have clinical implications for diagnosis, prognosis, and therapeutic response.

Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative.

OBJECTIVES: To evaluate the effect of a prospective opioid reduction intervention after radical prostatectomy (RP; based on a surgery-specific guideline and education) on post-discharge opioid prescribing, use, disposal, and need for additional opioid medication. PATIENTS AND METHODS: A prospective, non-randomised, pre-post interventional trial of patients undergoing RP for prostate cancer (August 2017-November 2018) was conducted as part of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. An evidence-based intervention including: a discharge sheet, nursing education, and standardised prescribing guideline, was applied with the primary outcome of total oral morphine equivalents (OMEQ) used after RP. Secondary outcomes included opioid prescribing, opioid disposal, need for additional opioid medication, and presence of incisional/post-surgical abdominal pain at 30 days after RP. RESULTS: A total of 214 (Pre-Intervention arm) and 229 (Post-Intervention arm) adult patients were enrolled (100% follow-up). The intervention reduced post-discharge opioid prescribing (from 224.3 to 120.3 mg; -46.4%, P = 0.01), reduced opioid use (from 52.1 to 38.3 mg; -26.5%, P < 0.01), and increased opioid disposal (+13.5%, P < 0.01). Greater prescribing of opioids at discharge, higher body mass index, and use of opioid medication prior to surgery, were independently associated with greater post-discharge opioid use, while history of a chronic pain diagnosis was not statistically significant. In the Post-Intervention cohort, 2.2% of patients needed additional medication for post-surgical pain (0.9% obtained a prescription) and 1.3% initiated long-term use. CONCLUSIONS: A prospective, evidence-based intervention reduced post-discharge opioid prescribing and use, while increasing disposal after RP. Risk factors for increased opioid use were identified. The results support expanding the use of evidence-based opioid reduction interventions to other surgical specialties.

Clinical, Pathological and Oncologic Findings of Radical Prostatectomy with Extraprostatic Extension Diagnosed on Preoperative Prostate Biopsy.

PURPOSE: Prostatic adenocarcinoma with extraprostatic extension detected on prostate needle biopsy is an uncommon finding. We describe clinical and pathological findings in a large cohort of patients with prostatic adenocarcinoma who were treated with radical prostatectomy and in whom extraprostatic extension was identified on prostate needle biopsy. MATERIALS AND METHODS: Using our institutional pathology database we identified 83 patients with prostatic adenocarcinoma and with extraprostatic extension on prostate needle biopsy between 2000 to 2018 who underwent radical prostatectomy and had clinical followup information. Clinical and pathological outcomes were examined. RESULTS: Of the 83 patients 54 (65%) presented with clinical stage T2 or greater disease. On biopsy 50 of the 83 patients (60%) had Grade Group 4-5 and 66 (81%) had perineural invasion. Extraprostatic extension was confirmed in the radical prostatectomy specimen in 81 of 83 cases (98%). At radical prostatectomy 49 of 83 patients (59%) had positive surgical margins, 37 (45%) had seminal vesicle invasion and 30 (37%) had lymph node involvement. Median followup after radical prostatectomy was 2 years. Overall 34 of 76 men (45%) received postoperative radiation a median of 1 year after radical prostatectomy and 8 (11%) received chemotherapy a median of 2 years after radical prostatectomy. The 3-year biochemical recurrence-free survival rate was 48.4% (95% CI 0.345-0.610) and the 3-year metastasis-free survival rate was 75.2% (95% CI 0.603-0.851). CONCLUSIONS: Patients in whom extraprostatic extension is detected on prostate needle biopsy almost always have extraprostatic disease and markedly adverse pathology findings at radical prostatectomy. Many of them experience biochemical recurrence and most will require multimodal therapy. These data can be useful to counsel such patients in regard to the treatment approach and the expected outcomes after surgery.

Establishment of a new prostate cancer multidisciplinary clinic: Format and initial experience.

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.

Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.

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.

Somatic HOXB13 Expression Correlates with Metastatic Progression in Men with Localized Prostate Cancer Following Radical Prostatectomy.

BACKGROUND: Homeobox B13 (HOXB13) expression regulates normal prostate development and mutations are associated with prostate cancer (PCa) formation. OBJECTIVE: To assess the role of HOXB13 mRNA expression in PCa progression following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide expression profiles were queried from two retrospective prostatectomy cohorts with follow-up data (Mayo Clinic, n=780; Johns Hopkins Medical Institute [JHMI], n=355), and a prospective genomic registry (n=5239). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox regressions were used to analyze metastasis-free survival (MFS). RESULTS AND LIMITATIONS: HOXB13 expression in primary PCa increased with increasing tumor grade and with high metastatic potential based on a genomic signature. The highest quartile of HOXB13 expression was associated with worse MFS compared with the lowest quartile (Mayo Clinic: adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 1.03-2.06, and JHMI: AHR 1.80, 95% CI 1.02-3.19). The combinations of high HOXB13 expression and low expression of its binding partner, MEIS1 (AHR 2.03, 95% CI 1.54-2.66) or MEIS2 (AHR 1.73, 95% CI 1.33-2.26), portended worse MFS. Additionally, high HOXB13 expression in combination with low MEIS1/2 expression correlated with high expression of androgen receptor-mediated genes. The retrospective nature of this study subjects the findings to a bias due to unmeasured variables. CONCLUSIONS: Primary PCa tumors with increased HOXB13 expression have an increased propensity for metastases following prostatectomy, particularly in the setting of low MEIS1/2 expression. High androgen receptor output may account for worse outcomes for these tumors and suggests heightened sensitivity to androgen suppression. PATIENT SUMMARY: Using genomic data from a large number of prostate cancer (PCa) tumors, we found that increased expression of homeobox B13 (HOXB13), a gene related to normal prostate development, was associated with worse outcomes following surgery for PCa. A biomarker signature suggests that these tumors would be more susceptible to androgen suppression, a common treatment for PCa. Take Home Messagece:: In multiple large cohorts, prostate cancer tumors with high homeobox B13 (HOXB13) expression and low expression of its binding partner MEIS1/2 were enriched with high androgen receptor output and had an increased propensity for metastases following surgery.

Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.

This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness.

Management of acute post-operative hemorrhage following partial nephrectomy with renal artery embolization.

Hemorrhage after robotic-assisted partial nephrectomy (RAPN) is uncommon but can cause significant morbidity. We present a case of acute hemorrhage isolated to the collecting system that was managed with renal artery embolization (RAE). A 76-year-old male developed sudden onset transfusion-dependent hematuria and hypotension following uncomplicated RAPN. He had no signs of intra-abdominal bleeding and his hypotension was responsive to volume resuscitation. Renal angiography identified a segmental artery with extravasation into the collecting system. RAE eliminated the patient's hematuria, the need for further transfusion, and allowed preservation of renal function. RAE is a viable option for collecting system hemorrhage following RAPN.

Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial.

BACKGROUND: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation. OBJECTIVE: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort. DESIGN, SETTING, AND PARTICIPANTS: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018). INTERVENTION: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed. RESULTS AND LIMITATIONS: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection. CONCLUSIONS: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection. PATIENT SUMMARY: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.

CDKN1B Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer.

PURPOSE: The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population. EXPERIMENTAL DESIGN: Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent of the genome with copy-number alterations (PGA). Cox proportional hazards analyses assessed the association of genomic alterations with risk of metastasis. RESULTS: At RP, 71% (145/205) of patients had grade group ≥3 disease, and 49% (99/202) were non-organ confined. The median PGA was 3.7% (IQR = 0.9%-9.4%) and differed by pathologic grade (P < 0.001) and stage (P = 0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had increased risks of metastasis (multivariable: HR = 13.45; 95% CI, 2.55-70.86; P = 0.002). The most common somatic mutations were SPOP (11.2%), FOXA1 (8.3%), and TP53 (3.9%). The most common loci altered at the copy number level were CDKN1B (6.3%), CHD1 (4.4%), and PTEN (3.4%). TP53 mutations and deep deletions in CDKN1B were associated with increased risks of metastasis on multivariable analyses (TP53: HR = 9.5; 95% CI, 2.2-40.6; P = 0.002; CDKN1B: HR = 6.7; 95% CI, 1.3-35.2; P = 0.026). CONCLUSIONS: Overall, PGA, somatic TP53 mutations, and a novel finding of deep deletions in CDKN1B were associated with poor prognosis in AA men. These findings require confirmation in additional AA cohorts.

SPINK1 expression is enriched in African American prostate cancer but is not associated with altered immune infiltration or oncologic outcomes post-prostatectomy.

BACKGROUND: The SPINK1 molecular subtype is more common in African-American (AA) men with prostatic adenocarcinoma (PCa) than European Americans (EA). Studies have suggested that SPINK1 expression is associated with more aggressive disease. However, the size, follow-up, and racial diversity of prior patient cohorts have limited our understanding of SPINK1 expression in AA men. The objective was to determine the associations between SPINK1 subtype, race, and oncologic outcomes after radical prostatectomy (RP). METHODS: A total of 186 AA and 206 EA men who underwent RP were matched according to pathologic grade. We examined SPINK1 status by immunohistochemistry on tissue microarrays using a genetically validated assay. Cox proportional hazard analyses assessed the association of SPINK1 status with oncologic outcomes in race-specific multivariate models. A second objective was to determine the correlation between CD3/CD8 T cell densities with SPINK1 status and race, using immunostaining and automated image analysis. RESULTS: SPINK1-positive subtype was present in 25% (45/186) of AA and 15% (30/206) of EA men (p = 0.013). There were no differences in pathologic grade, pathologic stage, biochemical recurrence (BCR)-free survival, or metastasis-free survival between SPINK1-positive and SPINK1-negative tumors in the overall cohort or by race. In multivariate analyses, SPINK1 expression was not associated with BCR (AA: HR 0.99, 95% CI 0.56-1.75, p = 0.976; EA: HR 0.88, 95% CI 0.43-1.77, p = 0.720) or metastasis (AA: HR 0.79, 95% CI 0.25-2.49, p = 0.691; EA: HR 1.55, 95% CI 0.58-4.11, p = 0.381) in either AA or EA men. There were no significant differences in surrounding CD3/CD8 lymphocyte densities between SPINK1-positive and SPINK1-negative tumors in either race. CONCLUSIONS: SPINK1-positive subtype is more prevalent in AA than EA men with PCa. Contrary to previous studies, we found that SPINK1 protein expression was not associated with worse pathologic or oncologic outcomes after RP in either AA men or EA men.

A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative.

Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017-2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models. PATIENT SUMMARY: In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.

Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.

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.

Reclassification rates are higher among African American men than Caucasians on active surveillance.

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.

Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.

PURPOSE: We studied the ethnicity-specific expression of prostate cancer (PC) -associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. PATIENTS AND METHODS: A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. RESULTS: Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). CONCLUSION: We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men.

Racial disparities in oncologic outcomes after radical prostatectomy: long-term follow-up.

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.