Background Black men in the US have substantially higher prostate cancer incidence rates than the general population. The extent to which the incidence disparity is due to prostate cancer being more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown. Methods We estimated three independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of PSA screening, based on the National Health Interview Survey in 2005, and prostate cancer incidence from the Surveillance, Epidemiology, and End Results program in 1975–2000. Using the estimated models, we compared prostate cancer natural history in black men and in the general population. Results The models projected that 30–43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28–56% higher than in the general population. Among men who have had preclinical disease onset, black men have a similar risk of diagnosis (35–49%) compared with the general population (32–44%), but their risk of progression to metastatic disease by the time of diagnosis is 44–75% higher than in the general population. Conclusions Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men.

Background Prostate-specific antigen (PSA) screening for prostate cancer has high risks of overdiagnosis, particularly in older men, and reports from screening trials indicate that it saves few lives after 11–13 years of follow-up. New clinical guidelines recommend against PSA screening for all men or for men over 70 years, but expected population effects of these guidelines have not been studied. Methods Two models of prostate cancer natural history and diagnosis were previously developed using reconstructed PSA screening patterns and prostate cancer incidence in the US. Assuming a survival benefit of PSA screening consistent with the screening trials, we used the models to predict incidence and mortality rates for the period 2013–2025 under continued PSA screening and under discontinued PSA screening for all men or for men over 70 years. Results The models predict that continuation of recent screening rates will overdiagnose 710,000–1,120,000 (range between models) men but will avoid 36,000–57,000 cancer deaths over the period 2013–2025. Discontinued screening for all men eliminates 100% of overdiagnoses but fails to prevent 100% of avoidable cancer deaths. Continued screening for men under 70 eliminates 64–66% of overdiagnoses but fails to prevent 36–39% of avoidable cancer deaths. Conclusions Discontinuing PSA screening for all men may generate many avoidable cancer deaths. Continuing PSA screening for men under 70 years could prevent more than half of these avoidable cancer deaths while dramatically reducing overdiagnoses relative to continued PSA screening for all ages.

Microabstract The kinetics and relationships between testosterone (T) and prostate-specific antigen (PSA) during the first off-treatment interval in men with non-metastatic prostate cancer treated prospectively on a clinical trial of intermittent androgen deprivation were analyzed. Time to PSA rise and time to PSA rise after first T>50 ng/dL were prognostic for progression to castration-resistance. Background Intermittent androgen deprivation (IAD) represents an alternative to continuous AD with quality-of-life benefit and no evidence of inferior overall survival for non-metastatic prostate cancer. Early markers of prognosis for men treated with IAD have not been described. Methods Men with non-metastatic prostate cancer were treated with 9 months of leuprolide and flutamide followed by a variable “off-treatment” interval; AD was resumed when prostate specific antigen (PSA) reached a pre-specified value (1 ng/mL - radical prostatectomy; 4 ng/mL - intact prostate). Cycles were repeated until castration-resistance (CRPC), defined as two PSA rises with testosterone (T) ≤50 ng/dL. We evaluated kinetics and relationships of PSA and T levels, focusing on times to rise in each level, during the first off-treatment interval. Associations with CRPC and prostate cancer mortality (PCM) were estimated using Cox proportional hazards models controlling for age and Gleason score. Results Each 30-day increase in time to PSA rise was associated with a 21% reduction in the risk of developing CRPC (95% CI, 3–36%; P=0.02). Longer time (≥60 days) to PSA rise after rise to T >50 ng/dL was associated with a 71% reduction in the risk of developing CRPC (95% CI, 92% reduction to 2% inflation; P=0.05). Time to first T >50 ng/dL and PSA doubling time were not prognostic for progression to CRPC. No time interval was prognostic for PCM. Conclusion During the first off-treatment interval of IAD, longer times to PSA rise overall and after T >50 ng/dL were associated with reduced risk of developing CRPC.

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