Joint Biochemical and Genetic Prostate Cancer Risk Stratification

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.

Keywords: PSA; polygenic hazard score; polygenic risk; prospective studies; prostatic neoplasms; risk assessment.