Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

被引：281

作者：

Castro, Elena ^{[1
,2
,3
]}

Goh, Chee ^{[2
,3
]}

Leongamornlert, Daniel ^{[2
,3
]}

Saunders, Ed ^{[2
,3
]}

Tymrakiewicz, Malgorzata ^{[2
,3
]}

Dadaev, Tokhir ^{[2
,3
]}

Govindasami, Koveela ^{[2
,3
]}

Guy, Michelle ^{[2
,3
]}

Ellis, Steve ^{[4
]}

Frost, Debra ^{[4
]}

Bancroft, Elizabeth ^{[2
,3
]}

Cole, Trevor ^{[5
]}

Tischkowitz, Marc ^{[6
]}

Kennedy, M. John ^{[7
,8
]}

Eason, Jacqueline ^{[9
]}

Brewer, Carole ^{[10
]}

Evans, D. Gareth ^{[11
]}

Davidson, Rosemarie ^{[12
]}

Eccles, Diana ^{[13
]}

Porteous, Mary E. ^{[14
]}

Douglas, Fiona ^{[15
]}

Adlard, Julian ^{[16
]}

Donaldson, Alan ^{[17
]}

Antoniou, Antonis C. ^{[4
]}

Kote-Jarai, Zsofia ^{[2
,3
]}

Easton, Douglas F. ^{[4
]}

Olmos, David ^{[1
]}

Eeles, Rosalind ^{[2
,3
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Clin Res Programme, Prostate Canc Unit, Madrid, Spain

[2] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England

[3] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England

[4] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[5] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England

[6] Univ Cambridge, Dept Med Genet, Cambridge, England

[7] Univ Dublin Trinity Coll, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland

[8] St James Hosp, Dublin 8, Ireland

[9] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England

[10] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England

[11] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England

[12] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland

[13] Univ Southampton, Fac Med, Southampton Univ Hosp NHS Trust, Southampton SO9 5NH, Hants, England

[14] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland

[15] Newcastle Upon Tyne Hosp NHS Trust, Ctr Life, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England

[16] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England

[17] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England

来源：

EUROPEAN UROLOGY | 2015年 / 68卷 / 02期

关键词：

BRCA1; BRCA2; Homologous repair; Prognostic factor; Prostate cancer; Prostatectomy; Radiotherapy; BREAST-CANCER; RADIOTHERAPY; CARRIERS; POLYMERASE; OUTCOMES; THERAPY; WOMEN; MEN;

D O I：

10.1016/j.eururo.2014.10.022

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：186 / 193

页数：8

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