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

Lookup NU author(s): Dr Fiona Douglas

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Abstract

© 2014 European Association of Urology. 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 in carriers (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.


Publication metadata

Author(s): Castro E, Goh C, Leongamornlert D, Saunders E, Tymrakiewicz M, Dadaev T, Govindasami K, Guy M, Ellis S, Frost D, Bancroft E, Cole T, Tischkowitz M, Kennedy MJ, Eason J, Brewer C, Evans DG, Davidson R, Eccles D, Porteous ME, Douglas F, Adlard J, Donaldson A, Antoniou AC, Kote-Jarai Z, Easton DF, Olmos D, Eeles R

Publication type: Article

Publication status: Published

Journal: European Urology

Year: 2015

Volume: 68

Issue: 2

Pages: 186-193

Print publication date: 01/08/2015

Online publication date: 06/11/2014

Acceptance date: 15/10/2014

ISSN (print): 0302-2838

ISSN (electronic): 1873-7560

Publisher: Elsevier

URL: http://doi.org/10.1016/j.eururo.2014.10.022

DOI: 10.1016/j.eururo.2014.10.022


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