Frequency of Germline and Somatic BRCA1 and BRCA2 Mutations in Prostate Cancer: An Updated Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Our updated systematic review and meta-analysis investigates the frequency of germline and somatic BRCA1 and BRCA2 mutations in patients with prostate cancer (PC), with subgroup analysis according to the type of mutation (germline or somatic mutations; mutation of BRCA1 and/or BRCA2) and according to the disease setting (any stage PC or metastatic PC or metastatic castration-resistant PC). As known, BRCA testing has recently become standard in clinical practice in prostate cancer because of new available target therapies. However, several open questions remain, in terms of the best time to perform it, the genes to look for (BRCA only or genes related to the DNA repair pathway of homologous recombination as well), and the optimal molecular analysis technique (somatic and/or germline testing or, in the future, liquid biopsy, which interestingly could assess both somatic and germline mutations simultaneously). ABSTRACT: In prostate cancer (PC), the presence of BRCA somatic and/or germline mutation provides prognostic and predictive information. Meta-analysis aims to estimate the frequency of BRCA mutations in patients with PC (PCp). In November 2022, we reviewed literature searching for all articles testing the proportion of BRCA mutations in PCp, without explicit enrichment for familiar risk. The frequency of germline and somatic BRCA1 and/or BRCA2 mutations was described in three stage disease populations (any/metastatic/metastatic castration-resistant PC, mCRPC). Out of 2253 identified articles, 40 were eligible. Here, 0.73% and 1.20% of any stage PCp, 0.94% and 1.10% of metastatic PCp, and 1.21% and 1.10% of mCRPC patients carried germline and somatic BRCA1 mutation, respectively; 3.25% and 6.29% of any stage PCp, 4.51% and 10.26% of metastatic PCp, and 3.90% and 10.52% of mCRPC patients carried germline and somatic BRCA2 mutation, respectively; and 4.47% and 7.18% of any stage PCp, 5.84% and 10.94% of metastatic PCp, and 5.26% and 11.26% of mCRPC patients carried germline and somatic BRCA1/2 mutation, respectively. Somatic mutations are more common than germline and BRCA2 are more common than BRCA1 mutations; the frequency of mutations is higher in the metastatic setting. Despite that BRCA testing in PC is now standard in clinical practice, several open questions remain.