Germline Mutations and Ancestry in Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results. RECENT FINDINGS: Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.

Time Matters: Importance of Circadian Rhythms, Disruption, and Chronotherapy in Urologic Malignancies.

The human body was evolutionarily programmed to run on cycles, termed circadian rhythms, which integrate human behavior and bodily function with the environment. Disruptions to these rhythms via desynchronization have been deemed a probable carcinogen by the WHO. Subsequent research has identified alterations in multiple core clock genes when comparing tumor and benign tissues. This review will discuss core clock genes associated with urogenital malignancies and highlight impactful research regarding circadian biology use in treatment. Chronotherapy, treatment alignment with an individual's biological rhythm, remains a relatively untouched field within urology that should be explored to possibly enhance therapeutic outcomes.

Estimating patient health in prostate cancer treatment counseling.

BACKGROUND: We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. METHODS: NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. RESULTS: Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with ≤10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). CONCLUSIONS: A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.

Race-specific prostate cancer outcomes in a cohort of low and favorable-intermediate risk patients who underwent external beam radiation therapy from 1990 to 2017.

BACKGROUND: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT). METHODS: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis. RESULTS: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. CONCLUSIONS: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care.