Metatastatic Relapse and Survival After Radical Treatment in Patients with Localised Prostate Cancer and BRCA Mutations

Conventional therapies less efficient in prostate cancer patients carrying BRCA mutations

Prostate cancer patients carrying inherited mutations in the BRCA genes respond less well to conventional treatment, including surgery and/or radiotherapy and they also have a lower survival rate than those who are non-carriers of these genetic mutations. Data from the study, which has been published in the journal European Urology, points to the need for new clinical trials aimed at targeting these mutations in order to tailor treatment for these patients. The study has been led by Drs David Olmos and Elena Castro at the Spanish National Cancer Research Centre (CNIO) and Rosalind Eeles at the Institute of Cancer Research & Royal Marsden NHS Foundation Trust in the UK. 

Olmos and Castro

CNIO researchers David Olmos and Elena Castro

The latest findings have roots in a 2013 study published by the same group of researchers in which they observed that patients carrying inherited mutations in the BRCA genes suffered from more aggressive tumours and died earlier. After these initial findings, the researchers decided to conduct a more in-depth study among patients with inherited BRCA mutations treated with radiotherapy or surgery.

According to the results, regardless of the treatment received, patients with tumours at a localised stage do not respond as well to the current treatments as in patients not carrying the mutations. Over 1,300 patients participated in the study, 67 of whom were carriers of BRCA mutations. Patients carrying such mutations who had undergone radiotherapy showed 10-year survival rates of 39%, compared to 80% for non-carriers.

Amongst patients who have undergone surgery the difference in 10-year survival rates is less pronounced (91% vs. 67%); the smaller difference in survival rates among carriers and non-carriers who have undergone surgery shows that "these patients may require more long-term monitoring to establish whether or not this difference is significant," argues Castro.

Importance of change in treatment strategy

Still to this day, the prognostic factors that would help determine a more personalised treatment are unknown. Smaller, less aggressive tumours are surgically removed; larger and/or more aggressive tumours are treated using surgery and radiation therapy. "An important issue is that during consultation we usually cannot predict which patients will evolve less favourably and which will live less time than others," the researchers explain. The team's objective is to identify the subgroup of patients with the least favourable prognosis and the treatments that best match their genetic characteristics.

Specific mutations in BRCA genes prevent damaged cells from repairing the DNA efficiently and have been associated with various types of cancer, including breast, ovarian and prostate cancer. PARP inhibitors, which are currently in clinical trials for the treatment of prostate cancer, are proving to be very effective in the treatment of breast and ovarian cancer when there are BRCA mutations. Furthermore, "prostate tumours with sporadic mutations (present only in the tumour, not inherited) in BRCA, also respond to these inhibitors, according to recent data presented during the ESMO (European Society for European Oncology) congress in Madrid," states Olmos.

The conclusions of this study underline the importance of launching clinical trials designed to assess new treatment strategies and the therapeutic potential of novel drugs for prostate cancer in these patients, such as PARP inhibitors.

Closer monitoring

This study has focused on prostate cancer patients with hereditary BRCA mutations. "We are investigating whether patients with sporadic mutations in these genes also show more aggressive and metastatic tumours, and whether or not they respond less well to conventional treatments than patients not carrying BRCA mutations."

If this hypothesis is confirmed "there would be a need for closer monitoring of patients with BRCA mutations, regardless of the origin (hereditary or sporadic), in order to improve the clinical course of these patients."

It is believed that 2% of prostate cancer patients are carriers of hereditary BRCA mutations, while 12% of the patients have sporadic mutations in the same genes.

The study has been financed by the Ronald and Rita McAulay Foundation, the CRIS Foundation for Cancer Research, the Spanish Association against Cancer (AECC), the GAME-ON initiative, and the European Union.

Reference

Castro E, Goh C, Leongamornlert D,et al.Effect of BRCA mutations on metatastatic relapse and cause-specific survival after radical treatment for localized prostate cancer. European Urology 2014; Published online 6 November. doi: 10.1016/j.eururo.2014.10.022