Objective: To evaluate population-based prostate cancer (CaP) testing of men in their 40s, given the paucity of prospective data evaluating the consequences of prostate-specific antigen (PSA) testing in younger men for CaP. Materials and Methods: A total of 1052 men in their 40s were followed longitudinally for prostate outcomes, from 1990 to 2010. A random subset of 268 men was selected to undergo biennial CaP testing including PSA testing, transrectal ultrasound, and a digital rectal examination. A representative population of 609 men with a subset of 159 men who also began CaP testing in their 50s was also evaluated as a comparison group. Risk of prostate biopsy (PBx), CaP, or death from CaP was compared between CaP-tested and the routine-care population cohort. Results: Median follow-up was 17.2 years. Men aged 40-49, who underwent CaP testing were 2.4 times more likely to undergo a PBx (hazard ratio [HR] 2.4 95% confidence interval [CI] 1.8-3.3) and 2.2 times more likely to be diagnosed with low-risk CaP (HR 2.2, 95% CI 1.12-4.0). Those initiating CaP testing a decade earlier were 2.2 times and 1.7 times more likely to be biopsied and be diagnosed with CaP for any given age (HR 2.2 95% CI 1.4-3.5 and 1.7 95% CI 1.1-2.7, respectively). Conclusion: CaP testing in men beginning at age 40 resulted in a significant increase in the risk of PBx and diagnosis of low-risk CaP, without a measurable reduction in risk of CaP-death in this low-risk population. However, given the natural history of CaP, a longer follow-up is needed to confirm this finding.
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