Incorporating Genetic Risk Into Prostate Cancer Care: Implications for Early Detection and Precision Oncology.

Abstract

The availability and cost of germline and somatic genetic testing have dramatically improved over the past two decades, enabling precision medicine approaches in oncology, with significant implications for prostate cancer (PCa) care. Roughly 12% of individuals with advanced disease are carriers of rare pathogenic germline variants that predispose to particularly aggressive and earlier-onset disease. Several of these variants are already established as clinically actionable by modern precision oncology therapeutics, while others may come to aid the selection of active surveillance, definitive local therapies, and systemic therapies. Concurrently, the number of common variants (ie, incorporated into polygenic risk scores) associated with PCa risk has continued to grow, but with several important considerations both at the intersection of race and ancestry and for early detection of aggressive disease. Family history has historically been used as a proxy for this inherited genetic risk of PCa, but recently emerging evidence examining this relation has shifted our understanding of how best to leverage this tool in PCa care. This review seeks to clarify and contextualize the existing and emerging precision oncology paradigms that use inherited genetic risk in PCa care, for both early detection and localized disease management.