BERKELEY, CA (UroToday.com) - BRCA2 germline mutations are the genetic event, known to date, associated with the highest risk of developing prostate cancer (RR 8.6 by age 65) (Kote-Jarai et al., BJC, 2011); the effect of BRCA1 is more modest (RR 4.6 by age 65). (Leongarmonlert, BJC, 2012). We previously demonstrated that these mutations are also a prognostic factor for prostate cancer outcomes, as mutation carriers have a worse outcome than non-carriers, independently of other prognostic factors such as PSA levels, Gleason score or TNM (Castro et al., JCO, 2013). In this paper recently published by European Urology, we wanted to analyze the response of carriers to conventional treatments for localized cancer (radical prostatectomy, RP, and external radiation therapy, RT). With over 1 300 men included in the analysis (67 of which harboured germline BRCA mutations), we showed that carriers have different responses to treatment than non-carriers, as summarized in Tables 1 and 2. BRCA carriers developed metastasis before non-carriers in both the RT and RP cohorts (Table 1). However, that did not have an impact on overall survival in those surgically treated; whilst on the contrary, carriers treated with RT had shorter survival than non-carriers.
Our results support close monitoring of BRCA mutations patients conventionally treated for prostate cancer, however the most appropriate management for this population is still unknown. PARP inhibitors have demonstrated to have an impact on the management of BRCA-mutated tumours and are currently approved for use in ovarian cancer. Prostate cancer patients with such mutations may benefit from the clinical trials with PARP inhibitors that are currently being conducted.
Germline BRCA mutations occur in less than 2% of sporadic prostate cancers, but somatic BRCA2 loss has been described in approximately 15% of cases. There is currently no indication for genetic testing, but as technologies evolve and the cost of sequencing decreases, it may prove cost-effective in the near future.
|Table 1: Metastasis-free survival of carriers and non-carriers by treatment types|
|Table 2: Overall survival of carriers and non-carriers by treatment types|
Elena Castro, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Clinical Investigator, Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Honorary Consultant in Medical Oncology & Cancer Genetics, Hospital Universitario Madrid Norte Sanchinarro, 28029 Madrid, Spain