Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer
Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer
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DOI：
10.1016/j.eururo.2014.10.022
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发表时间：
2015-08-01
期刊：
影响因子：
23.4
通讯作者：
Eeles, Rosalind
中科院分区：
文献类型：
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作者：
Castro, Elena;Goh, Chee;Eeles, Rosalind
背景资料：生殖系BRCA突变与前列腺癌（PCa）预后恶化相关;然而，突变携带者最合适的治疗方法尚未研究。目的：通过分析根治性前列腺切除术（RP）或外束放射治疗（RT）后的无转移生存期（MFS）和病因特异性生存期（CSS），评估BRCA携带者对局部PCa常规治疗的反应。和与会者：分析了1302例局部/局部晚期PCa患者（包括67例BRCA突变携带者）的肿瘤特征和结局。535例患者接受RP（35例BRCA）; 767例接受RT（32例BRCA）。中位随访时间为64个月。结果测量和统计分析：使用Kaplan-Meier方法估计中位生存率和3年、5年和10年生存率。使用对数秩检验比较生成的生存曲线。考克斯回归分析被用来评估BRCA基因突变的预后价值。结果和局限性：共67 BRCA携带者和1235名非携带者。在治疗后3、5和10年，97%、94%和84%的非携带者和90%、72%和50%的携带者无转移（p < 0.001）。非携带者队列的3年、5年和10年CSS率（分别为99%、97%和85%）显著优于携带者队列（分别为96%、76%和61%; p < 0.001）。多变量分析证实BRCA突变是MFS的独立预后因素（风险比[HR]：2.36; 95%置信区间[CI]：1.38-4.03; p = 0.002）和CSS（HR：2.17; 95% CI，1.16-4.07; p = 0.016）。当对局部/局部晚期PCa进行常规治疗时，BRCA携带者的预后比非携带者差。生殖系BRCA突变的前列腺癌患者在常规手术或放射治疗时的预后比非携带者差。(C)2014年欧洲泌尿外科协会。Elsevier B. V.出版，保留所有权利。
Background: Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated.Objective: To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT).Design, setting, and participants: Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo.Outcome measurements and statistical analysis: Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations.Results and limitations: A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (p < 0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than incarriers (96%, 76%, and 61%, respectively; p < 0.001). Multivariate analysis confirmed BRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p = 0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p = 0.016).Conclusions: BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa.Patient summary: Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.