EAU 2018: Case-Based Debate: BRCA 1/2 Testing Before Treatment of Metastatic Castration-Resistant Prostate Cancer - Ready for Prime Time

Copenhagen, Denmark (UroToday.com) Dr. Nelson gave an overview of why BRCA 1 and 2 testing should be done before treatment of metastatic castrate resistant prostate cancer (MCRPC) patients.  His talk summarized 10 points on why it is prime time for genetic testing before treating these patients.

  1. There is a high frequency of pathogenic germline mutations. Pritchard et al. demonstrated that 11.8% of MCRPC patients were shown to have deleterious germline mutations in 16 DNA repair genes, in a New England Journal of Medicine (NEJM) published paper. [1]
  2. There is high frequency of pathogenic somatic events in these patients. Over 25% of patients were with deleterious somatic events in DNA repair genes. [2]
  3. Testing is prognostic and predictive. The incidence of BRCA 1 mutations are twice as common in MCRPC patients, with earlier onset. In BRCA 2 mutation the incidence of MCRPC is 4-6 times as common, with earlier onset and higher grade at diagnosis.
  4. Increased risk of other malignancies. BRCA mutations confer a higher risk for male breast cancer (8 times more common), pancreatic cancer (4-5 times more common) and others (melanoma).
  5. Testing will enable us to identify male and female family members at risk, and this early detection could potentially allow us to prevent disease development.
  6. Understand the penetrance of the disease.
  7. Enable us to enroll patients in clinical trials. There are currently at least 20 trials enrolling patients with BRCA mutations, assessing the effect of different treatments.
  8. Allow us to administer PARP inhibitors to these patients. An NEJM paper demonstrated an benefit for metastatic prostate cancer patients with DNA-repair gene mutations who were treated with the PARP inhibitor Olaparib.[3]
  9. Platinum therapy – data has shown that these patients have exceptional response to platinum chemotherapy. [4]
  10. The guidelines recommend testing! According to the NCCN guidelines for MCRPC patients it is recommended to consider tumor testing for Microsatellite instability (MSI) or DNA mismatch repair gene mutations. It is recommended to test the following genes: BRCA 1+2, ATM, PALB2, FANCA.
In conclusion, there is sufficient amount of evidence to support genetic testing in MCRPC patients.

Presented by: P. Nelson, Seattle, WA, US

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark
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