针对患有前列腺癌 (PC) 和非 BRCA1/2 同源重组修复 (HRR) 突变的男性的 DNA 损伤疗法的结果数据有限。我们通过聚（ADP-核糖）聚合酶抑制剂（PARPi）和/或铂类化疗治疗的男性 PC 患者的 HRR 变化来评估结果。使用了来自 PROMISE 联盟的回顾性数据。评估了 BRCA1/2 突变患者（A 组）和没有直接 BRCA 复合物相互作用的 HRR 突变患者（B 组：ATM、CDK12、CHEK1、CHEK2 和 FANCL）之间的临床结果差异。还探讨了具有直接 BRCA 复合物相互作用的 HRR 突变患者的结果（队列 C：RAD51B/C/D、RAD54L2、BARD1、GEN1、PALB2、FANCA 和 BRIP1）。 146 名患者接受了 PARPi（队列 A） ：94 人，B 组：45 人，C 组：7 人）和 104 人接受了铂类化疗（A 组：48 人，B 组：44 人，C 组：10 人）。队列 A 中 PSA50 对 PARPi 的反应率 (61%) 高于队列 B (5%)，P < .001。 A 组中 PARPi 的中位临床/放射学无进展生存期 (crPFS) 显着长于 B 组：15.9 个月与 8.7 个月，P = 0.005。队列 A 中对铂类治疗的 PSA50 反应率 (62%) 高于队列 B (32%)，P = 0.024，尽管 crPFS 没有显着差异。在队列 C 中，对 PARPi 和铂类化疗的 PSA50 应答率分别为 40% 和 32%。在多变量分析中，与接受 PARPi 但不接受铂类化疗的队列 B 相比，队列 A 显着改善了总生存率和 crPFS。 BRCA1/2- 患者与那些没有直接 BRCA 复合物相互作用的 HRR 突变的患者相比，突变的 PC 显着改善了 PARPi 的结果，但没有铂化疗的效果。

Outcomes data for DNA-damaging therapeutics for men with prostate cancer (PC) and non-BRCA1/2 homologous recombination repair (HRR) mutations are limited. We evaluated outcomes by HRR alteration in men with PC treated with poly(ADP-ribose)polymerase inhibitors (PARPi) and/or platinum chemotherapy.Retrospective data from the PROMISE consortium were used. Clinical outcomes differences were assessed between patients with BRCA1/2 mutations (cohort A) and those with HRR mutations without direct BRCA complex interaction (cohort B: ATM, CDK12, CHEK1, CHEK2, and FANCL). Outcomes in patients with HRR mutations with direct BRCA complex interaction were also explored (cohort C: RAD51B/C/D, RAD54L2, BARD1, GEN1, PALB2, FANCA, and BRIP1).One hundred and forty-six patients received PARPi (cohort A: 94, cohort B: 45, cohort C: 7) and 104 received platinum chemotherapy (cohort A: 48, cohort B: 44, cohort C: 10). PSA50 response rate to PARPi was higher in cohort A (61%) than cohort B (5%), P < .001. Median clinical/radiographic progression-free survival (crPFS) with PARPi in cohort A was significantly longer than in cohort B: 15.9 versus 8.7 months, P = .005. PSA50 response rate to platinum therapy was higher in cohort A (62%) than in cohort B (32%), P = .024, although crPFS was not significantly different. PSA50 response rate to PARPi and platinum was 40% and 32%, respectively, in cohort C. In multivariable analysis, cohort A had significantly improved overall survival and crPFS compared with cohort B with PARPi but not platinum chemotherapy.Patients with BRCA1/2-mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.