PSA Screening Benefits and Harms: Systematic Review for the American Cancer Society Guideline Update

A systematic review synthesized the evidence on the benefits and harms of prostate-specific antigen (PSA)-based screening for prostate cancer to inform an updated guideline from the American Cancer Society. Searches of PubMed and the Cochrane Central Register of Controlled Trials covered literature through December 4, 2023, and were updated through October 29, 2025. Eligible studies comprised randomized and nonrandomized comparisons of PSA-based screening strategies versus no screening or alternative screening strategies, incorporating low- and medium-risk of bias systematic reviews supplemented by subsequent studies.

The review evaluated 29 publications: two publications from a 2018 systematic review of the PLCO, CAP, and ERSPC trials; 23 subsequent publications spanning six trials (PLCO, CAP, ERSPC, Göteborg-1, Rotterdam Pilot 1, and ProScreen); and four observational studies. Dual-investigator abstraction, independent risk of bias assessment, and strength-of-evidence evaluations were conducted.

PSA-based screening was associated with reduced incidence of advanced or metastatic prostate cancer at diagnosis and a lower cumulative incidence of metastatic disease. However, it was also associated with increased detection of low-risk prostate cancer. Reductions in prostate cancer–specific mortality were observed in some trials, but overall findings were inconsistent and likely depended on variations in screening protocols, PSA thresholds, participant characteristics, and other factors. In addition, the review identified several screening-associated harms, including overdiagnosis, false-positive test results, biopsy-related complications, and downstream treatment harms.