Prostate cancer screening is crucial for attenuating morbidity and mortality^{22 23 2425}. However, the traditional method of PSA screening is infamous for false-positive rate and potential harm due to overtreatment of benign disease²⁶²⁷. The US Preventive Service Task Force recommended the consideration of family history and race/ethnicity to identify men who would benefit the most from early PSA screening. While family history and race/ethnicity are indirect assessments of inherited risk, which can be prone to environmental exposures, PRS creates an opportunity to directly measure inherited PCa risk. A cohort study of 3225 men showed that PRS acts as an independent predictor for PCa; thereby, incorporating PRS into the current risk prediction model based on family history, PSA and age could create a better stratification tool with improved predictive capacity²⁷²⁸. Even among unbiopsied men with low level of serum PSA of 1-3 ng/ml, PRS can be used to predict biopsy outcomes and identify men with high PCa risk²⁹. PRS’s predictive power offers an informative tool to target PSA screening efforts for men with a higher risk of early PCa onset and to guide decisions for a more active clinical approach to those with a higher risk of aggressive PCa²⁷³⁰ (Figure 1) Additionally, there is evidence indicating that the cumulative effect of known polygenic risk factors can modify the risk estimate of mutations in BRCA1 and BRCA2, with penetrance of BRCA1 and BRCA2 varying as much as 26% and 61% respectively, depending on whether the individual is at the 5th or 95th percentile of prostate cancer³¹.

Figure 1: Utilization of PRS to predict individual risk of prostate cancer (Created using BioRender.com)