Abstract
PURPOSE: Overdiagnosis of prostate cancer (PC) through PSA testing at short intervals remains common. While baseline serum PSA abundance < 1 ng/mL warrants infrequent screening, it is critical to foster advanced diagnostic practices for men with baseline serum PSA ≥ 1 ng/mL, who are at higher risk for clinically significant disease. We investigated whether common germline variants could enhance screening recommendations in men with PSA ≥ 1 ng/mL. MATERIALS AND METHODS: Polygenic hazard scores (PHS) for the risk of PC diagnosis (PHS290) were computed in a diverse, matched, prospective cohort of 310 men with baseline PSA ≥ 1 ng/mL with or without PC. Regression models were used to predict PC clinical risk groups with PHS290, while incorporating clinical covariates and an existing 5-year risk calculator score. RESULTS: PHS290 stratified individuals with PSA ≥ 1 ng/mL into risk groups and identified men with intermediate-risk and high-risk PC. Adding PHS290 to our model for predicting time to intermediate-risk and high-risk PC improved predictions over an existing prebiopsy 5-year risk calculator. CONCLUSIONS: Our study demonstrates the potential of genetic scores to advance screening guidance. The PC risk stratification capabilities of molecular biomarkers in tiered screening strategies merit further study in large cohorts.