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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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。

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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

期刊介绍： BJUI is one of the most highly respected medical journals in the world, with a truly international range of published papers and appeal. Every issue gives invaluable practical information in the form of original articles, reviews, comments, surgical education articles, and translational science articles in the field of urology. BJUI employs topical sections, and is in full colour, making it easier to browse or search for something specific.