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Prostate cancer screening incurs a high risk of overdiagnosis and overtreatment. An organized and age-targeted screening strategy may reduce the associated harms while retaining or enhancing the benefits. Using a micro-simulation analysis (MISCAN) model, we assessed the harms, benefits, and cost-effectiveness of 230 prostate-specific antigen (PSA) screening strategies in a Dutch population. Screening strategies were varied by screening start age (50, 51, 52, 53, 54, and 55), stop age (51-69), and intervals (1, 2, 3, 4, 8, and single test).