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Eur Urol. 2015 Aug;68(2):186-93. doi: 10.1016/j.eururo.2014.10.022. Epub 2014 Nov 6.

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

Author information

1
Prostate Cancer Unit, Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: ecastro@cnio.es.
2
Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
3
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
4
West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK.
5
Department of Medical Genetics, University of Cambridge, Cambridge, UK.
6
Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St. James's Hospital, Dublin, Ireland.
7
Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
8
Department of Clinical Genetics, Royal Devon and Exeter Hospital, Exeter, UK.
9
Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
10
Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK.
11
University of Southampton Faculty of Medicine, Southampton University Hospitals NHS Trust, Southampton, UK.
12
South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK.
13
Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
14
Yorkshire Regional Genetics Service, Leeds, UK.
15
Clinical Genetics Department, St. Michael's Hospital, Bristol, UK.
16
Prostate Cancer Unit, Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Electronic address: dolmos@cnio.es.

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.

KEYWORDS:

BRCA1; BRCA2; Homologous repair; Prognostic factor; Prostate cancer; Prostatectomy; Radiotherapy

PMID:
25454609
DOI:
10.1016/j.eururo.2014.10.022
[Indexed for MEDLINE]

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