Prostate-specific antigen (PSA)–based testing for detection of prostate cancer has remained controversial since its widespread adoption by clinicians in the United States in the late 1980s. Although measurement of PSA blood levels was approved in 1995 by the US Food and Drug Administration for early detection, PSA levels are not specific for prostate cancer or the more aggressive forms of the disease, which include approximately 1 in 3 newly diagnosed prostate cancers. In a randomized screening trial that included 162 388 patients, low specificity resulted in prostate biopsies in 20% of men screened,1 cancer was not detected in 3 of every 4 biopsies performed,2 and 70% of cancers detected in the screening group were found to be low grade (nonaggressive form).3 Prostate biopsies carry the risk of bleeding and infection requiring hospitalization in from 0.5% to 6.9% of men.4 However, these harms are less concerning than the rates of overdiagnosis (ie, detection of cancers that would not have been detected during life in the absence of screening), estimated to be from 23% to 42% in the US population and as high as 67% in a randomized screening trial conducted in Europe.5 If treated, these men risk a reduction in quality of life in urinary, sexual, and bowel domains6,7 without the benefit of extending life, because they would not have known about their cancer in the absence of screening.