Castro E, et al. - In this prospective multicenter cohort study, researchers evaluated the prevalence of germline DNA damage repair mutations (ATM/BRCA1/BRCA2/PALB2 germline mutations) and determined how these mutations influence metastatic castration-resistance prostate cancer (mCRPC) outcomes. Outcomes revealed the deleterious impact of germline BRCA2 (gBRCA2) mutations on mCRPC outcomes. gBRCA2 status was identified significantly interacting with treatment type (androgen signaling inhibitor v taxane therapy). They observed greater cause-specific survival (CSS) (24.0 v 17.0 months) and progression on the second systemic therapy (PFS2) (18.9 v 8.6 months) in gBRCA2 carriers treated in the first line with abiraterone or enzalutamide compared with taxanes. These findings support the determination of gBRCA2 status to select the initial treatment in mCRPC.