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- PMID: 25454609
- UKPMCID: 25454609
- DOI: 10.1016/j.eururo.2014.10.022
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Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer.
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. 2014;.
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Full-text held externally
- PMID: 25454609
- UKPMCID: 25454609
- 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.
Keyword(s)
BRCA1; BRCA2; Homologous repair; Prognostic factor; Prostate cancer; Prostatectomy; Radiotherapy
Bibliographic metadata
- 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