研究同源重组修复 (HRR) 特别是乳腺癌癌症 1/2 (BRCA1/2) 基因的改变对总生存 (OS) 的影响。此外，探讨抑制聚（ADP-核糖）聚合酶（PARPi）作为转移性去势抵抗性前列腺癌（mCRPC）全身治疗的效果。对所有HRR筛查的转移性前列腺癌患者进行基线特征采样。 Kaplan-Meier 估计和多变量 Cox 回归模型预测了 HRR/BRCA1/2 改变对 OS 的影响。在 196 名符合条件的患者中，61 名 (31%) 存在任何 HRR，40 名 (20%) 存在 BRCA1/2 改变。在 HRR 改变中，40 (66%) vs 6 (10%) vs 5 (8.2%) vs 4 (6.6%) vs 2 (3.3%) vs 4 (6.6%) 是 BRCA1/2 vs 共济失调毛细血管扩张突变激酶 ( ATM）与检查点激酶 2 (CHEK2) 与细胞周期蛋白依赖性激酶 12 (CDK12) 与范可尼贫血补充 A 组 (FANCA) 与其他突变阳性相比。其中，30% 获得了 PARPi。 HRR 阳性患者与 HRR 阴性患者的 OS 存在显着差异。特别是在激素敏感型前列腺癌中，中位 OS 为 63（HRR 阳性）vs 57（BRCA1/2 阳性）vs 113 个月（HRR 阴性）（P ≤ 0.01）。在 mCRPC 中，OS 分别为 42（HRR 阳性）vs 41（BRCA1/2 阳性）vs 70 个月（HRR 阴性）（P ≤ 0.01）。多变量调整后，HRR 和 BRCA1/2 改变与较差的 OS 相关。最后，未接受 PARPi 治疗的患有 BRCA1/2 突变的 mCRPC 患者的 OS 比患有 BRCA1/2 突变且接受 PARPi 治疗的患者更差（中位 OS：33 个月 vs 48 个月，P<0.03）。 临床现实世界中 HRR 改变的发生率当使用基于血液和组织的测试时，设置较高。 HRR/BRCA 改变的患者预后较差，导致使用或不使用 PARPi 的 HRR/BRCA 阳性 mCRPC 患者与 HRR/BRCA 阴性患者之间的 OS 存在显着差异。© 2024 作者。 BJU International 约翰·威利 (John Wiley) 出版

To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC).Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS.Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03).Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.