Germline Genetics of Prostate Cancer: Prevalence of Risk Variants and Clinical Implications for Disease Management

SIMPLE SUMMARY: Advances in our understanding of the molecular basis of prostate cancer have resulted in the discovery of a subset of patients harboring germline variants that places them at increased risk of developing the disease. The goal of precision oncology in prostate cancer is to individualize treatments by tailoring them to the genetic characteristics of each patient’s cancer. Management of advanced prostate cancer is rapidly evolving with genomic-driven therapies. We provide a comprehensive overview of the current guideline recommendations for germline testing in prostate cancer. Expanding the use of genetic testing in prostate cancer patients can inform treatment strategies. We discuss prostate cancer germline genomic profiling and its impact on decision making of therapeutic options. ABSTRACT: Prostate cancer has entered into the era of precision medicine with the recent approvals of targeted therapeutics (olaparib and rucaparib). The presence of germline mutations has important hereditary cancer implications for patients with prostate cancer, and germline testing is increasingly important in cancer screening, risk assessment, and the overall treatment and management of the disease. In this review, we discuss germline variants associated with inherited predisposition, prostate cancer risk and outcomes. We review recommendations for germline testing, available testing platforms, genetic counseling as well as discuss the therapeutic implications of germline variants relevant to prostate cancer treatments. Understanding the role of germline (heritable) mutations that affect prostate cancer biology and risk as well as the subsequent effect of these alterations on potential therapies is critical as the treatment paradigm shifts towards precision medicine. Furthermore, enhancing patient education tactics and healthcare system infrastructure is essential for the utilization of relevant predictive biomarkers and the improvement of clinical outcomes of patients with prostate cancer or at high risk of developing the disease.