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

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

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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Phenotype
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatectomy* / adverse effects
  • Prostatectomy* / mortality
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United Kingdom

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen