Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

IF 3.7 2区医学 Q1 UROLOGY & NEPHROLOGY

BJU International Pub Date : 2025-01-01 Epub Date: 2024-07-10 DOI:10.1111/bju.16462

Mike Wenzel, Benedikt Hoeh, Florestan Koll, Clara Humke, Anne Fassl, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Miriam Traumann, Severine Banek, Felix K H Chun, Philipp Mandel

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引用次数: 0

Abstract

Objective: 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).

Patients and methods: 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.

Results: 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).

Conclusion: 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.

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同源重组修复/乳腺癌（BRCA）基因改变对转移性前列腺癌患者生存期的影响。

研究目的研究同源重组修复（HRR），尤其是乳腺癌1/2（BRCA1/2）基因的改变对总生存期（OS）的影响。此外，探讨多聚（ADP-核糖）聚合酶（PARPi）抑制剂作为转移性去势抵抗性前列腺癌（mCRPC）全身疗法的效果：对所有接受HRR筛查的转移性前列腺癌患者的基线特征进行抽样调查。Kaplan-Meier估计值和多变量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 人（31%）有任何 HRR 改变，40 人（20%）有 BRCA1/2 改变。在HRR改变中，40例（66%） vs 6例（10%） vs 5例（8.2%） vs 4例（6.6%） vs 2例（3.3%） vs 4例（6.6%）为BRCA1/2 vs共济失调-特朗吉克斯突变激酶（ATM） vs检查点激酶2（CHEK2） vs细胞周期蛋白依赖性激酶12（CDK12） vs范可尼贫血补体A组（FANCA） vs其他突变阳性。其中30%的患者接受了PARPi治疗。HRR阳性与阴性患者的OS差异很大。具体来说，激素敏感性前列腺癌的中位生存期为 63 个月（HRR 阳性）vs 57 个月（BRCA1/2 阳性）vs 113 个月（HRR 阴性）（P ≤ 0.01）。在 mCRPC 中，OS 为 42 个月（HRR 阳性）vs 41 个月（BRCA1/2 阳性）vs 70 个月（HRR 阴性）（P ≤ 0.01）。经多变量调整后，HRR和BRCA1/2改变与较差的OS相关。最后，未接受PARPi治疗的BRCA1/2突变mCRPC患者的OS比BRCA1/2突变并接受PARPi治疗的患者更差（中位OS：33个月 vs 48个月，P≤0.01）：中位OS：33个月 vs 48个月，P在临床实际环境中，使用基于血液和组织的检测方法，HRR 改变的发生率很高。HRR/BRCA变异患者的预后较差，导致使用或不使用PARPi的HRR/BRCA阳性mCRPC患者与HRR/BRCA阴性患者的OS差异显著。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BJU International 医学-泌尿学与肾脏学

CiteScore

9.10

自引率

4.40%

发文量

262

审稿时长

1 months

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