Genetic testing and management of prostate cancer patients with pathogenic germline variants

Prostate cancer (PCa) is an androgen-receptor signaling-dependent disease with a subset of patients harboring pathogenic germline variants (PGVs) in genes essential for DNA repair. In the last decade, several guidelines and recommendations have been developed to define which PCa patients should receive genetic testing to identify individuals at higher risk due to inherited alterations and to facilitate personalized treatment strategies. Notably, the presence of specific germline alterations in carriers undergoing PCa screening has implications for screening strategies, and PGV carriers with advanced disease are eligible to receive targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi) or immune checkpoint inhibitors (CKI) depending on the alterations encountered. Although less information is available on carriers with localized disease, several trials are addressing this specific patient population and will help to collect data and improve clinical management of PCa patients with PGVs.