A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

New EAU/ASCO guideline recommendations on sentinel node biopsy for penile cancer and remaining challenges from a nuclear medicine perspective.

INTRODUCTION: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide. MAIN TEXT: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates. CONCLUSION: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.

A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers.

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. RESULTS: Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. CONCLUSIONS: The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.

Clinicopathological analysis and outcomes of inflammatory myofibroblastic tumours of the urinary bladder.

OBJECTIVES: To describe clinical, imaging, and histopathological characteristics of inflammatory myofibroblastic tumour (IMT) of the urinary bladder and provide initial management and surveillance recommendations. PATIENTS AND METHODS: We identified patients with IMT of the bladder treated at our facility from 1998 to 2020. Categorical variables were analysed with chi-square and Fisher's exact tests and continuous variables with the Mann-Whitney U-test. Kaplan-Meier analysis was performed for recurrence-free survival. RESULTS: IMT was diagnosed in 35 patients with median (interquartile range [IQR]) follow-up of 20 (11.5-68.5) months. At initial diagnosis 86% were clinically organ-confined, 9% locally advanced, and 5% metastatic. Majority of patients (92%) had residual disease on re-staging transurethral resection (TUR). Of the 15 patients with organ-confined disease managed initially with TUR alone, five (33%) recurred at a median (IQR) of 5 (3.0-5.5) months from initial diagnosis. Presentation with visible haematuria was associated with recurrence (100% in recurrence vs 40% in non-recurrence groups, P = 0.044). There were no patients who developed a recurrence beyond 6 months after diagnosis. Partial or radical cystectomy was required in 23% and 9% of patients, respectively. One patient presented with metastatic disease associated with anaplastic lymphoma kinase (ALK) translocation and achieved a durable complete remission with 7 months of crizotinib therapy. CONCLUSIONS: No patient with IMT treated with aggressive endoscopic management developed recurrences beyond 6 months. There were additionally no recurrences noted after definitive radical or partial cystectomy. These data support organ sparing therapy with aggressive endoscopic management and short-term surveillance in patients with localised IMT, with extirpative surgery reserved for refractory cases.

Pembrolizumab for advanced penile cancer: a case series from a phase II basket trial.

BACKGROUND: Treatment options for unresectable, locally advanced or metastatic penile squamous cell carcinoma (SCC) are limited. Previous studies have shown that 40-62% of patients with penile SCC express PD-L1. We report three cases of locally advanced or metastatic penile SCC treated with pembrolizumab. CASE PRESENTATIONS: Herein, we present three patients with recurrent, locally advanced or metastatic penile SCC who progressed on a platinum-based chemotherapy triplet and were treated with pembrolizumab, administered as part of a phase II clinical trial for rare tumors (NCT02721732). One patient with a microsatellite instability high (MSI-H) tumor experienced a durable partial response to pembrolizumab, underwent surgical consolidation, and remains disease-free 38.7 months later. Two patients experienced progressive disease within 3 months of beginning pembrolizumab. No one experienced a grade 3 or worse treatment-related adverse event. CONCLUSION: In sum, single-agent pembrolizumab was well tolerated as salvage therapy in a small cohort of patients with unresectable, locally advanced or metastatic penile SCC. Pembrolizumab produced an objective response in an MSI-H tumor, yet it did not control disease in two patients with MSS penile SCC. Rationale combination therapies, including pembrolizumab, warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02721732 . Registered March 23, 2016.

Leukocyte telomere length is associated with aggressive prostate cancer in localized African American prostate cancer patients.

Telomeres play important roles in cancer initiation and progression. Leukocyte telomere length (LTL) has been associated with the risk and prognosis of several cancers, but its association with prostate cancer (PCa) prognosis in African Americans (AAs) has not been reported. In this study, we measured relative LTL from 317 AA PCa patients and assessed its associations with aggressive disease characteristics at diagnosis and biochemical recurrence (BCR) after radical prostatectomy and radiotherapy. LTL was shorter in patients with higher Gleason scores (GS) at diagnosis. Dichotomized into short and long LTL groups, patients with short LTL exhibited a 1.91-fold (95% confidence interval, CI, 1.14-3.20, P = 0.013) increased risk of being diagnosed with high-risk disease (GS =7 [4 + 3] and GS ≥8) than those with long LTL in multivariable logistic regression analysis. Moreover, shorter LTL was significantly associated with an increased risk of BCR (hazard ratio = 1.68, 95% CI, 1.18-11.44, P = 0.024) compared with longer LTL in localized patients receiving prostatectomy or radiotherapy in multivariable Cox analysis. Kaplan-Meier survival analysis showed patients with short LTL had significantly shorter BCR-free survival time than patients with long LTL (Log rank P = 0.011). In conclusion, our results showed for the first time that LTL was shorter in PCa patients with higher GS and short LTL was associated with worse prognosis in AA PCa patients receiving prostatectomy or radiotherapy.

Intraoperative and early postoperative complications in postchemotherapy retroperitoneal lymphadenectomy among patients with germ cell tumors using validated grading classifications.

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Methylation of global DNA repeat LINE-1 and subtelomeric DNA repeats D4Z4 in leukocytes is associated with biochemical recurrence in African American prostate cancer patients.

Global DNA methylation may play important roles in cancer etiology and prognosis. The goal of this study is to investigate whether the methylation of long interspersed nucleotide elements (LINE-1) and subtelomeric DNA repeats D4Z4 in leukocyte DNA is associated with aggressive prostate cancer (PCa) in African Americans. We measured DNA methylation levels of LINE-1 and D4Z4 in 306 African American (AA) PCa patients using pyrosequencing and compared their methylation levels among clinical variables. We further applied multivariate Cox proportional hazards model and Kaplan-Meier survival function and log-rank tests to assess the association between DNA methylation and biochemical recurrence (BCR). Overall, there was no significant difference of the methylation levels of LINE-1 and D4Z4 among patients with different clinical and epidemiological characteristics. However, the methylation of LINE-1 and D4Z4 was associated with BCR. Patients with lower LINE-1 methylation and higher D4Z4 methylation exhibited markedly increased risks of BCR with adjusted hazard ratios of 3.34 (95% confidence interval, 1.32-8.45) and 4.12 (95% confidence interval, 1.32-12.86), respectively, and significantly shorter BCR-free survival times. Our results suggest that lower global DNA methylation and higher subtelomeric region methylation may predict worse prognosis in localized AA PCa patients.

Comparative analysis of p16 expression among African American and European American prostate cancer patients.

BACKGROUND: Expression of p16 is increased in a number of malignancies, including prostate cancer (PCa). Recent studies in a European cohort showed that expression of p16 is correlated with expression of the TMPRSS2/ERG (T/E) fusion protein. The T/E fusion is significantly less common in PCas in African American (AA) men. Thus, it would be predicted that p16 expression should be less common in PCas in AA men. We, therefore, sought to compare the expression of p16 in benign prostate and PCas from AA and European American (EA) men. METHODS: Immunohistochemistry for p16 and ERG was performed on tissue microarrays constructed from radical prostatectomies performed on AA and EA veterans. Staining was scored and the scores compared with demographic, clinical and pathological parameters. Percent of West African ancestry in the AA cohort was assessed using ancestry informative markers. RESULTS: Contrary to our predictions, p16 expression was similar in the cancers in the AA and EA cohorts. Consistent with prior reports, expression of p16 was quite low in benign prostate tissues from EA patients but surprisingly was significantly higher in benign tissues from AA patients. Expression of p16 was significantly associated with a family history of PCa in AA men. In addition, p16 was associated with ERG expression in AA PCa. CONCLUSIONS: While overall expression of p16 is similar in PCas from the two racial groups, the expression of p16 in benign tissues from a subset of AA men and the stronger correlation with ERG expression implies that there are different mechanisms for p16 overexpression in PCas from the two racial groups.

Genetics and penile cancer: recent developments and implications.

PURPOSE OF REVIEW: We summarize the recent developments in the molecular landscape of penile squamous cell carcinoma (PSCC). RECENT FINDINGS: Recent genomic studies have demonstrated a molecular convergence of PSCC with other squamous cell carcinomas (SCCs) from different organ sites. Similarly, human papillomavirus (HPV)-related PSCCs appear to have epigenetic and genomic similarities with other HPV-related cancers. This could have implications on future HPV-related cancer trial design. Growing efforts to characterize recurrent gene alterations in PSCC have expanded our understanding over the past years, showing a predominance of tumor suppressor gene alterations such as TP53 and NOTCH1. In addition, these studies have demonstrated that at least 30% of PSCC cases have targetable gene alterations. Further, the similar tumor mutational burden with other SCCs and the relatively high rates of programmed death-1 (PD-1) positive expression in PSCC constitute the rationale for investigation of PD-1 inhibition in ongoing clinical trials. Multiple studies have identified potential epigenetic and RNA signatures predictive of metastasis or survival, but these still require validation in larger cohorts. SUMMARY: PSCC appears to be genomicaly similar to other SCCs and HPV-related cancers. This provides the rationale and opportunity to include a rare tumor like PSCC in future 'basket type' trials using novel agents targeting multiple SCCs that may exhibit similar biology.

African American and Asian males: what do we know about germline predisposition to prostate cancer.

There is a paucity of data related to highly penetrant genes associated with a genetic predisposition to prostate cancer or its virulence among men of diverse ancestral populations including African American and Asian men. We review the recent published literature to gain insights into whether such genetic alterations previously described among Caucasians are noted among African American and Asian prostate cancer patients.

Baseline and longitudinal plasma caveolin-1 level as a biomarker in active surveillance for early-stage prostate cancer.

OBJECTIVES: To evaluate the role of caveolin-1 (Cav-1) as a predictor of disease reclassification (DR) in men with early prostate cancer undergoing active surveillance (AS). PATIENTS AND METHODS: We analysed archived plasma samples prospectively collected from patients with early prostate cancer in a single-institution AS study. Of 825 patients enrolled, 542 had ≥1 year of follow-up. Baseline and longitudinal plasma Cav-1 levels were measured using an enzyme-linked immunosorbent assay. Tumour volume or Gleason grade increases were criteria for DR. Logistic regression analyses were used to assess associations between clinicopathological characteristics and reclassification risk. RESULTS: In 542 patients, 480 (88.6%) had stage cT1c disease, 542 (100.0%) had a median prostate-specific antigen level of 4.1 ng/mL, and 531 (98.0%) had a median Cancer of the Prostate Risk Assessment score of 1. In all, 473 (87.3%) had a Gleason score of 3+3. After a median of 3.1 years of follow-up, disease was reclassified in 163 patients (30.1%). The mean baseline Cav-1 level was 2.2 ± 8.5 ng/mL and the median 0.2 ng/mL (range, 0-85.5 ng/mL). In univariate analysis, baseline Cav-1 was a significant predictor for risk of DR (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.24-2.65; P = 0.002). In multivariate analysis, with adjustments for age, tumour length, group risk stratification and number of positive cores, reclassification risk associated with Cav-1 remained significant (OR 1.91, 95% CI 1.28-2.84; P = 0.001). CONCLUSION: Baseline plasma Cav-1 level was an independent predictor of disease classification. New methods for refining AS and intervention may result.

Quality of life after brachytherapy or bilateral nerve-sparing robot-assisted radical prostatectomy for prostate cancer: a prospective cohort.

OBJECTIVE: To provide comparative data on quality of life (QoL) after prostate cancer treatment to help patients make an informed decision regarding their choice of treatment. METHODS: Patients with pathologically proven, non-metastatic, T1-T3bN0 prostate cancer were included in this prospective non-randomized study if they were to receive treatment with curative intent. Sample size was at least 181 patients per cohort/treatment type. QoL was recorded at baseline and at each follow-up using the Expanded Prostate Cancer Index Composite (EPIC) instrument. The minimal clinically important difference was defined as half of the standard deviation of the baseline score for each domain. A mixed effects model was used to compare the different treatments. Data are presented on the brachytherapy and the bilateral nerve-sparing robot-assisted radical prostatectomy (RARP) cohorts. Hormonotherapy was not allowed. RESULTS: Between November 2007 and January 2013, 181 patients who received brachytherapy and 210 patients who underwent RARP were included. Of the patients who underwent RARP, 178 had bilateral nerve-sparing and were included in the present analysis. Response rate to EPIC questionnaires were higher in the brachytherapy than in the RARP arm: 82% vs 57% at 2 years after treatment and 55% vs 45% at 4 years after treatment. In the mixed effects model, patients in the RARP arm had better QoL with regard to urinary irritation/obstruction or bother and bowel function, and lower QoL regarding sexual function and urinary incontinence. Results were confirmed in a propensity score-matched model. Patient satisfaction was significantly higher in the brachytherapy group at 1, 2 and 3 years after treatment. CONCLUSION: This prospective non-randomized study shows long-term differences in QoL domains after bilateral nerve-sparing RARP and brachytherapy. Differences in patient satisfaction should be further explored. These results could be used to counsel patients in the decision-making process.

Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.

Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men.

BACKGROUND: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. METHODS: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA < 2.5 ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS ≤ 7[3 + 4]), TS ≤ pT2) and high risk (GS≥ 7[4 + 3], TS > pT2) PCa. Statistical analyses were done using SAS. RESULTS: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P < 0.0001) and PR (P = 0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P = 0.034). CONCLUSION: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

BACKGROUND: The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). METHODS: A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. RESULTS: Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. CONCLUSIONS: Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society.

Impact of ethnicity on the outcome of men with metastatic, hormone-sensitive prostate cancer.

BACKGROUND: Prostate cancer (PCa) outcomes are impacted by socioeconomic and biologic factors. Ethnicity plays a role in the former, but little is known about the responsiveness of metastatic PCa to androgen-deprivation therapy (ADT) among races. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify men who were diagnosed with distant, de novo, metastatic PCa from 2004 to 2012. Patterns of presentation, overall survival (OS), and PCa-specific mortality (PCSM) were determined for each race. E3805 clinical trial data also were retrospectively reviewed to assess outcomes of ADT and ADT plus docetaxel by race. RESULTS: Of all PCa diagnoses in SEER, distant, de novo, metastatic disease was diagnosed in 4.2% of non-Hispanic whites, 5.8% of Hispanic whites, 5.7% of blacks, 5.5% of Asians/Pacific Islanders, and 8.8% of American Indians/Alaska Natives (P < .001; chi-square test). The median OS differed by race, with superior OS observed among Asian men (30 months) than among men of other races (range, 24-25 months; P < .001). Asians also had a superior median PCSM (54 months) compared with the other races (range, 35-40 months; P < .001). In E3805, chemohormonal therapy was associated with a median OS of 58.1 months (95% confidence interval, 48.8-72.9 months) and 57.6 months (95% confidence interval, 27.7-57.6 months) in non-Hispanic whites and blacks, respectively. Few Asians participated in the E3805 trial. CONCLUSIONS: Asian men have superior median OS and PCSM for distant, de novo, metastatic PCa than men of other race. Non-Hispanic whites and blacks who receive treatment with ADT or chemohormonal therapy have comparable outcomes. Cancer 2017;123:1536-1544. © 2017 American Cancer Society.

Factors associated with regional recurrence after lymph node dissection for penile squamous cell carcinoma.

OBJECTIVE: To identify factors associated with regional recurrence after lymph node dissection (LND) for squamous cell carcinoma (SCC) to determine which patients might benefit from adjuvant therapy. PATIENTS AND METHODS: Men who underwent LND for penile SCC from 1977 to 2014 were identified from an institutional database. Kaplan-Meier curves estimated recurrence-free survival (RFS) calculated from the date of LND. Cox regression models evaluated the association between RFS and patient and tumour characteristics. RESULTS: In all, 182 men who underwent LND for penile SCC were identified. The median patient age was 62 years and the median follow-up was 4.2 years. After LND 34 men had regional recurrence, of which 24 developed isolated regional recurrences without distant metastasis. The median RFS was 5.7 months, and the 3-year RFS rate was 70%. On univariate analysis, lymphovascular invasion, clinical and pathological nodal stage, pathological inguinal laterality, pelvic nodal involvement, lymph node density ≥5.2%, ≥3 pathologically involved lymph nodes, and extranodal extension (ENE) were associated with worse RFS (all P < 0.05). On multivariate analysis, clinical N3 disease [adjusted hazard ratio (AHR)] 3.53, 95% confidence interval (CI) 1.68-7.45; P = 0.001), ≥3 pathologically involved lymph nodes (AHR 3.78, 95% CI 2.12-6.65; P < 0.001), and ENE (AHR 3.32, 95% CI 1.93-5.76; P < 0.001) were associated with worse RFS. The 3-year RFS for patients with cN0, cN1, cN2, and cN3 disease was 91.7%, 64.5%, 54.7%, and 38.3%, respectively. For men with ≥3 involved nodes, the 3-year RFS was 17% vs 82.4% in men with <3 involved nodes. The 3-year RFS was 29.7% in men with ENE and 85.7% in men without ENE. CONCLUSION: The presence of clinical N3 disease, ≥3 pathologically involved lymph nodes, and ENE was associated with worse RFS. As regional recurrence portends a dismal prognosis with few salvage options, adjuvant therapies should be developed for men with the aforementioned adverse factors.