In men diagnosed with PCa, DNA-methylation profiling can detect under-sampled high-risk PCa in prostate biopsy specimens through a field effect. Predictive accuracy increased when EpiScore was combined with other clinical risk factors. These results suggest that EpiScore could aid in the detection of occult high-grade disease at the time of diagnosis, thereby improving the selection of candidates for Active Surveillance.

Concerns about overtreatment of clinically indolent prostate cancer (PrCa) have led to recommendations that men who are diagnosed with low‐risk PrCa be managed by active surveillance (AS) rather than immediate definitive treatment. However the risk of underestimating the aggressiveness of a patient's PrCa can be a significant source of anxiety and a barrier to patient acceptance of AS. The uncertainty is particularly keen for African American (AA) men who are about 1.7 times more likely to be diagnosed with PrCa than European American (EA) men and about 2.4 times more likely to die of this disease. The AA population, as many other populations in the Americas, is genetically heterogeneous with varying degrees of admixture from West Africans (WAs), Europeans, and Native Americans (NAs). Recommendations for PrCa screening and management rarely consider potential differences in risk within the AA population. We compared WA genetic ancestry in AA men undergoing standard prostate biopsy who were diagnosed with no cancer, low‐grade PrCa (Gleason Sum 6), or higher grade PrCa (Gleason Sum 7‐10). We found that WA genetic ancestry was significantly higher in men who were diagnosed with PrCa on biopsy, compared to men who were cancer‐negative, and highest in men who were diagnosed with higher grade PrCa (Gleason Sum 7‐10). Incorporating WA ancestry into the guidelines for making decisions about when to obtain a biopsy and whether to choose AS may allow AA men to personalize their approach to PrCa screening and management.

Objectives To determine the safety, efficacy and pharmacokinetic (PK) profile of a pre-mixed depot formulation of leuprolide mesylate subcutaneous injectable suspension (LMIS) 50 mg for up to 1 year of treatment for subjects with advanced prostate cancer. Patients and methodsIn this open-label, multicenter study, prostate cancer patients with indication for androgen ablation therapy received two subcutaneous injection of LMIS 50 mg 6 months apart and were followed for an additional 6 months. Two efficacy primary end points were the percentage of subjects with a serum testosterone level ≤ 50 ng/dL by Day 28 as well as the percentage of subjects with similar testosterone suppression from Day 28 to Day 336. Results Of the 137 enrolled subjects, 15 (10.9%) subjects did not complete the study, including 5 subjects who terminated early due to an adverse event. By Day 28, 98.5% (95% confidence interval 94.8-99.8) of the subjects achieved a castrate testosterone level. At the end of the study, 97% and 95.9% of the subjects had serum testosterone level ≤ 50 ng/dL and ≤ 20 ng/ dL, respectively. LMIS 50 mg significantly reduced serum prostate-specific antigen levels after its first injection and this PSA declination effect remained until the end of the study. No statistically significant change was observed in worsening bone pain or urinary symptom assessments during the study. Hot flush (48.9%) and hypertension (14.6%) were the two most common adverse events reported. Conclusions LMIS 50 mg, administered at 6-month intervals, effectively suppressed serum testosterone level, and demonstrated a consistent safety profile.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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established from among controls as in prior publications. In PHS, median PSA was 1.10, 75th percentile was 2.2, and 90th was 3.40. In SCCS, median PSA was 0.9, 75th percentile was 1.4 and 90th was 2.8. We created both unweighted and weighted genetic risk scores (GRS) based on SNPs identified to be associated with PSA in the Hoffman et al. Nat Genet. 2017 GWAS of PSA levels. GRS was used to adjust PSA values and then we assessed logistic regression models and AUC results.RESULTS: In PHS, compared to men with PSA < median, the age-adjusted odds ratio (OR) for men with PSA > 75th was OR 3.1 (95% CI 1.8, 5.3. When including the GRS, the adjusted OR for men with PSA > 75th improved to OR 3.4 (95% CI 1.9, 5.9) compared to men with a PSA < median. Age adjusted AUC was 0.64 (95% CI 0.59, 0.70) and GRS adjusted AUC was 0.65 (95% CI 0.59, 0.70). In SCCS, compared to men with PSA < median, the age-adjusted odds ratio (OR) for men with PSA > 75th was OR 27.9 (95%CI 12.0, 64.9). The GRS adjusted OR for men with PSA > 75th improved to OR 30.3 (95%CI 12.8, 71.7) compared to a PSA < median. The age and GRS adjusted AUC were 0.87 (0.83, 0.91). 21% (81/392) in PHS and 18% (56/319) of men in SCCS were reclassified by one quintile category using the PSA value adjusted for GRS with most movement in the middle quintiles.CONCLUSIONS: We found that the GRS adjusted baseline PSA modestly improved prediction of total and aggressive prostate cancer especially in men with moderately elevated PSA levels. It is possible that adjustment for genetic determinants of PSA may remove variation in levels unrelated to future cancer risk.