More than 164,000 cases of prostate cancer are diagnosed in the United States each year, according to the American Cancer Society. Four out of five cases are localized to the prostate, and the five-year survival rate for those patients is 100%. The survival rate is equally high when cancer spreads to nearby areas of the body. But when the disease metastasizes to lymph nodes, bone or distant organs, the five-year survival rate drops to approximately 29%.
Almost everyone is aware of the BRCA1/2 gene mutation and its linkage with increased risk for breast and ovarian cancer. But we now understand the BRCA mutations also can be linked with aggressive prostate cancer. Men who have these mutations in their DNA are known as germline mutations. Men who have BRCA1 mutation have up to four times greater risk of developing prostate cancer and those with BRCA2 have up to nine-fold higher risk. BRCA2 mutations have been associated with the more aggressive forms of the disease and an earlier diagnosis -- meaning diagnosed at age 55 or younger.
The current standard of care for metastatic prostate cancer is the same for all men, regardless of BRCA status. The first step is to figure out whether cancer responds to treatments which reduce the levels of testosterone in the body (castration sensitive) or whether it is resistant to this treatment (castration-resistant).
Men with castration-sensitive prostate cancer are treated with testosterone suppression known as androgen deprivation therapy. The tumours will respond for many years, but will at some point, become castration-resistant. The patients will then experience a rise in PSA, scans may show new areas of metastasis or patients may develop new cancer symptoms. Other treatments may be added, such as chemotherapy and/or radiation. Surgical removal of the prostate is also a treatment option for men with castration-sensitive or resistant cancer that has not yet spread.
A growing number of oncology clinics are genomic testing to guide treatment in men whose cancer has been castration-resistant. Previously, genetic testing was offered to prostate cancer patients of Ashkenazi Jewish descent for a family history of breast or ovarian cancer, but now consideration should be given to test all castration-resistant patients for therapeutic benefit, along with considerations for family members.
There is a treatment called PARP inhibitor that has been used successfully to treat ovarian and breast cancer patients with BRCA2 mutations because it blocks an enzyme which cells need to repair their DNA. The presence of a BRCA gene mutation, plus a PARP inhibitor, creates “synthetic lethality” and causes the cells to die.
Genetic testing is still rare in the treatment of prostate cancer.
Healthy men from families with histories of breast and ovarian cancer could benefit from knowing their BRCA status, which will help their physician design a surveillance plan to detect prostate cancer early. PAA testing has been controversial because it sometimes detects tumours that don’t need to be treated, and this may lead to unnecessary medical intervention. But because BRCA1 and BRCA2 mutations have been associated with the most aggressive, fastest-moving forms of prostate cancer, an abnormal PSA result in a man with one of those mutations might be taken more seriously.
Men who carry BRCA mutations might also face a higher risk of other cancers, including breast cancer, pancreatic cancer and melanoma. Patients can talk to their doctors as to how to screen for these cancers.
By Dr Monica Rocco
