BRCA mutations and response to conventional treatments for localised prostate cancer

The authors aimed to determine the effects of conventional treatment in localised prostate cancer patients with BRCA mutations.

BRCA mutations are mutations in the BRCA1 or BRCA2 gene (regulates cell functions). BRCA genes prevent tumors from growing. When they are mutated tumors can grow freely causing cancers such as breast, ovarian and prostate cancer.

There are several treatments suitable for localised prostate cancer (cancer is confined to the prostate). Radical prostatectomy is a treatment option that involves surgically removing the prostate and surrounding tissue. Radiation therapy is another form of treatment that uses radiation to kill cancer cells, however it can also damage normal cells so it needs to be carefully planned to minimize damage. Androgen deprivation therapy (ADT) is a treatment that targets the hormones used in prostate cancer.

The aim of this article was to determine how BRCA mutations affect a patients response to treatment in localised prostate cancer.

1,302 patients who had undergone either prostatectomy or radiation therapy were used in this study. 67 carried BRCA mutations – 18 BRCA1 and 49 BRCA2. Follow-up time was 67 months. Those with BRCA mutations more often had higher grade cancer (cells look more abnormal under the microscope) and larger tumors compared with non-carriers. 

535 patients received a radical prostatectomy, 35 BRCA carriers and 500 non-carriers. 767 patients received radiation therapy, 32 BRCA carriers and 735 non-carriers. Patients receiving radiation had a more aggressive, advanced disease. 78% of patients received ADT; 65% of BRCA carriers received ADT for more than 6 months compared to 41% of non-carriers.

127 patients experienced metastatic disease (cancer has spread outside the prostate to other organs). Following radical prostatectomy, 96% of BRCA carriers and 89% of non carriers were metastasis free after 3 years. After 5 years, 67% of BRCA carriers and 97% of non-carriers were metastasis free. After 10 years, 67% of BRCA carriers and 91% of non-carriers were metastasis free.

Following radiation therapy, 85% of BRCA carriers and 96% of non-carriers were free from metastasis after 3 years. After 5 years, 57% of BRCA carriers and 91% of non-carriers were metastasis free. After 10 years,  39% of BRCA carriers and 80% of non-carriers were metastasis free.

Having a BRCA mutation was associated with 2.36 times the risk of experiencing metastasis. 

After treatments, cause-specific survival (time after treatment that patient survives cancer in the absence of other causes of death) at 3 years was 96% in BRCA carriers and 99% in non-carriers, after 5 years was 76% in BRCA carriers and 97% in non-carriers and after 10 years was 61% in BRCA carriers and 85% in non-carriers.

Having a BRCA mutation was associated with 2.17 times the risk of cancer-related death, 

The authors conclude that BRCA carriers have worse outcomes after treatment and progress more quickly to metastatic disease when given conventional treatment.

The patient groups treated with radiation had more aggressive forms of cancer so cannot be accurately compared to patients who received a radical prostatectomy. 

If you are a BRCA carrier considering radical prostatectomy or radiation therapy and have concerns about the effectiveness of the treatment, please consult your doctor.