Prostate cancer patients carrying inherited mutations in the BRCA genes respond less well to conventional treatment, including surgery and 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 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.
10-Year Survival Reduced by Half
The findings originate from 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. "That was when we found the first genetic factor associated with prostate cancer prognosis," explains Castro.
It was then that the researchers decided to conduct a more in-depth study of patients with inherited BRCA mutations and the treatments applied to them, radiotherapy or surgery. According to the article, the results are unambiguous: regardless of the treatment received, patients with tumours at a localised stage (that is, non-metastatic tumours) do not respond as well to the current treatments as 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%; see table); 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.
Change of Treatment Strategy for these Patients
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 researcher explains. 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.
BRCA genes produce proteins that block tumour development, thereby guaranteeing the stability of the genetic material in cells; when the DNA gets damaged by environmental, hereditary or other factors, BRCA proteins come into play to fix it and therefore guarantee the survival of the cells. Specific mutations in these genes prevent damaged cells from repairing the DNA efficiently and have been associated with various types of cancer, including breast, ovarian and prostate cancer.