Abstract
Simple SummaryAdvances 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.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.
Highlights
Prostate cancer (PCa) is the second most common malignancy worldwide
Compared to other ethnic and racial groups around the world, African American (AA) and Black men have the highest incidence of PCa, mortality rates, and are more likely to develop the malignancy at an earlier age
In contrast to TOPARP-B, PROfound was a randomized, open-label, phase 3 trial designed to detect a difference in imaging-based progression-free survival following treatment with olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with abiraterone or enzalutamide and have either a germline or somatic mutations in BRCA1, BRCA2 or ATM (Cohort A, n = 162)
Summary
Prostate cancer (PCa) is the second most common malignancy worldwide. With an estimated 1.4 million new PCa cases and 375,000 deaths worldwide, the incidence of PCa and mortality rates are expected to continue to increase in the future [1]. The implementation of tumor genomic profiling for the detection of clinically relevant germline variants have enabled significant advances in the treatment of cancers with an inherited component such as breast, ovarian, and colon cancers. Despite such advances in a precision medicine approach for other cancers, PCa treatment options have lagged behind this transition to broader biomarker targeted approaches beyond androgen receptor (AR) pathway modulating therapeutics. PCa patients have consistently had better outcomes overall with a 5-year relative survival rate of 98.4% compared to lung and breast cancers [4] Despite these survival rates, treatment resistance and metastatic disease are still commonplace, affecting patient quality of life and outcomes [3]. It is of paramount importance to understand the role of germline (heritable) mutations that affect PCa biology and risk as well as the subsequent effect of these alterations on potential therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
