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

• Published in: European urology 2015-08, Vol.68 (2), p.186-193
• Main Authors: Castro, Elena, Goh, Chee, Leongamornlert, Daniel, Saunders, Ed, Tymrakiewicz, Malgorzata, Dadaev, Tokhir, Govindasami, Koveela, Guy, Michelle, Ellis, Steve, Frost, Debra, Bancroft, Elizabeth, Cole, Trevor, Tischkowitz, Marc, Kennedy, M. John, Eason, Jacqueline, Brewer, Carole, Evans, D. Gareth, Davidson, Rosemarie, Eccles, Diana, Porteous, Mary E, Douglas, Fiona, Adlard, Julian, Donaldson, Alan, Antoniou, Antonis C, Kote-Jarai, Zsofia, Easton, Douglas F, Olmos, David, Eeles, Rosalind
• Format: Article
• Language: English
• Subjects: BRCA1; BRCA1 Protein - genetics; BRCA2; BRCA2 Protein - genetics; Disease-Free Survival; DNA Mutational Analysis; Genetic Predisposition to Disease; Germ-Line Mutation; Homologous repair; Humans; Kallikreins - blood; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Phenotype; Prognostic factor; Proportional Hazards Models; Prostate cancer; Prostate-Specific Antigen - blood; Prostatectomy; Prostatectomy - adverse effects; Prostatectomy - mortality; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Radiotherapy; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United Kingdom; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2014.10.022

Abstract 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.