Although lung cancer remains the leading cause of death from cancer in American men, prostate cancer ranks as the most commonly diagnosed cancer except for skin cancer, with a lifetime risk for diagnosis of 15.9%. Over 240,000 American men received a prostate cancer diagnosis in 2011 and an estimated 33,720 men died of the disease. Prostate cancer is, however, a heterogeneous disease, as evidenced by autopsy studies which have shown that one-third of men age 40–60 have histologic evidence of prostate cancer. Such findings suggest that many cases of prostate cancer do not ever become clinically evident, raising concerns about the potential for overdiagnosis, defined as when a condition is diagnosed that would not go on to cause symptoms or death if it had not been discovered.

Neither of the two major trials of PSA screening have demonstrated benefit in terms of overall or all-cause mortality. The U.S.-based Prostate, Lung, Colon, and Ovarian (PLCO) Cancer Screening Trial was a multi-center study which randomized 76,693 men and found screening was associated with a 22% increase in prostate cancer diagnoses after 7 years of follow-up. Despite this, no difference in prostate cancer mortality was demonstrated at 7 years and 10 years of follow-up. Although the European Randomized Study of Screening for Prostate Cancer (ERSPC) found that PSA-based screening reduced the rate of prostate cancer death by 21% after a median follow-up of 11 years, it failed to show a reduction in all-cause mortality. Based on their data, the ERSPC investigators estimated that to prevent one death from prostate cancer, 1055 men would need to be invited for screening and 37 cancers would need to be detected.

The U.S. Preventive Services Task Force (USPSTF) has concluded that a substantial percentage of men who have asymptomatic prostate cancer detected by PSA screening have a tumor that would have remained asymptomatic for the man’s lifetime. Following a review of the benefits and harms of PSA screening and the treatment of localized prostate cancer, in 2012 the USPSTF recommended against PSA-based screening for prostate cancer for all men in the general U.S. population regardless of age (USPSTF D recommendation).