In this issue of JAMA, Martin and colleagues1 report the results of the third, and with more than 400 000 participants by far the largest, randomized trial of prostate-specific antigen (PSA) screening for prostate cancer. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) joins the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial (about 77 000 participants) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (about 162 000 participants) in attempting to settle the question of the balance of benefits and harms from PSA screening.2,3 In this cluster randomized trial, 573 primary care practices in the United Kingdom offered men aged 50 to 69 years a single PSA screening test or usual care. The mean age of the 419 582 participants was 59 years and about 40% of the participants treated at the practices randomized to the intervention group accepted the invitation to be screened, a degree of dilution of the intervention consistent with the prediction of screening uptake included in the trial’s power calculation.