Screening Men at Increased Risk for Prostate Cancer Diagnosis: Model Estimates of Benefits and Harms

Roman Gulati, Heather H Cheng, Paul H Lange, Peter S Nelson, Ruth Etzioni

Guidelines for prostate-specific antigen (PSA) screening in subgroups with increased risk of prostate cancer (PCa) diagnosis due to race or genotype are underdeveloped. Our goal was to investigate types of increased PCa risk and implications for targeted screening. Computer simulation of subgroups with average and hypothetical increased risk(s) of onset of latent disease, progression, and/or cancer-specific death. For each subgroup, we predicted lifetime probabilities of overdiagnosis and life saved under more and less intensive PSA screening strategies. An application estimated risks of onset among BRCA1/2 mutation carriers in the IMPACT study using maximum likelihood. Our simulations implied PSA screening can save more lives among subgroups with increased risk than with average risk, but more intensive screening did not always improve harm-benefit tradeoffs. IMPACT data were consistent with increased risks of onset among BRCA1 and BRCA2 mutation carriers (HR=1.05, 95% CI 0.63-1.59 and HR=1.81, 95% CI 1.14-2.78, respectively). Our analysis suggests screening BRCA2 mutation carriers earlier and more frequently than the average-risk population, but a lower PSA threshold for biopsy is unlikely to improve outcomes. Effective screening in men with increased PCa risk depends on the manner in which the risk is increased. More intensive screening is not always optimal. Guidelines for screening men at increased PCa risk should consider the mechanism inducing the increased risk. While the benefit of screening may be greater in men with increased risks, more intensive screening is not always appropriate.