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  • Effect of BRCA Mutations on...
    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

    European urology, 08/2015, Letnik: 68, Številka: 2
    Journal Article

    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.