Prevalence of germline BRCA1/2 pathogenic variants in Japanese patients treated with castration-resistant prostate cancer and efficacy of CRPC treatment in real-world clinical practice

Objective The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer.Methods Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx (R). Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed.Results Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149).Conclusions In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer. In total, 6.5% of patients carried the germline BRCA1/2 pathogenic variants, exhibiting poor prognosis and poor clinical response to androgen receptor-axis-targeted therapy and taxane chemotherapy for castration-resistant prostate cancer.