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Reducing the Harm of Prostate Cancer Screening: Repeated Prostate-Specific Antigen Testing. OBJECTIVE: To determine if repeating a prostate-specific antigen (PSA) test in men with an elevated PSA level is associated with a decreased risk of prostate biopsy and cancer diagnosis. PATIENTS AND METHODS: A cohort of patients referred to the Ottawa Regional Prostate Cancer Assessment Clinic from April 1, 2008, through May 31, 2013, who had referral PSA levels between 4 and 10 ng/mL were included in the study. Univariate and multivariate associations between a normal result on repeated PSA testing and the risk of prostate biopsy, cancer diagnosis, and Gleason score of 7 or higher were examined. RESULTS: The study cohort included 1268 patients. Repeated PSA test results were normal in 315 patients (24.8%). Men with normal results on repeated PSA testing were younger (mean ± SD age, 61.5±8.2 years vs 65.2±8.2 years; P<.001) and had lower referral PSA levels (mean ± SD, 5.5±1.4 ng/mL vs 6.6±1.5 ng/mL; P<.001) than men with an abnormal repeated PSA result. In multivariate analysis, men with normal results on repeated PSA testing were less likely to undergo prostate biopsy (relative risk [RR], 0.42; 95% CI, 0.34-0.50) and were at lower risk for cancer diagnosis (RR, 0.22; 95% CI, 0.14-0.34) and Gleason score of 7 or higher (RR, 0.16; 95% CI, 0.08-0.34) compared with men who had an abnormal repeated PSA test result. CONCLUSION: Routinely repeating a PSA test in patients with an elevated PSA level is independently associated with decreased risk of prostate biopsy and prostate cancer diagnosis. Men with an elevated PSA level should be given a repeated PSA test before proceeding to biopsy.