Experts who convened at the 2019 Philadelphia Prostate Cancer Consensus Conference created a multidisciplinary prostate cancer genetic implementation framework tailoring treatment to the precision medicine era.
The conference included experts, stakeholders, and national organization leaders — including from the National Comprehensive Cancer Network — who were convened to address challenges in prostate cancer germline evaluation and implementation. To establish consensus on topics, votes were cast anonymously; 75% or greater agreement was considered a strong consensus, 50% to 74% was considered a moderate consensus, and less than 50% was considered a lack of consensus.
The first question addressed was which men should be considered for germline prostate cancer genetic testing. The panel recommended testing among all men with metastatic prostate cancer, and men with 1 brother or father or 2 more male relatives diagnosed with prostate cancer aged younger than 60, who died from prostate cancer, or who had metastatic prostate cancer. Testing should be considered in men with nonmetastatic disease who are of Ashkenazi Jewish ancestry, who have advanced disease, intraductal/ductal pathology, are grade group 4 or above, or who had a family history of 2 or more cancers in the Lynch syndrome spectrum.
Continue Reading
Another important consideration for the panel was which testing panels should be considered and which genes should be prioritized. For men with metastatic disease, comprehensive genetic testing should be done, the panel agreed. Testing should include BRCA2/BRCA1, DNA mismatch repair (MMR) genes, ATM, and additional genes based on family history.
The third question posed to the panel was what prostate cancer-specific recommendations should be considered on the basis of genetic results (ie, how will results inform treatment). Among the recommendations were that men with metastatic or nonmetastatic prostate cancer with a BRCA2 mutation may respond to PARP inhibition. Men with other mutations, such as BRCA1, should be considered for clinical trials, and those with DNA MMR gene mutations may respond to anti-PD-1 therapy.
The fourth question was how to obtain optimal informed consent. Here the panel recommended discussing “(1) the purpose of genetic testing; (2) the possibility of uncovering hereditary cancer syndromes; (3) potential types of test results; (4) the potential to uncover additional cancer risks; (5) potential out-of-pocket cost; (6) Genetic Information Nondiscrimination Act law and other laws that address genetic discrimination; and (7) cascade testing/ additional familial testing.”
The remaining questions addressed collaborative strategies for genetic evaluation between healthcare and genetic providers, post-test disclosure strategies, and barriers to genetic testing. Further recommendations and considerations were given for each question addressed by the panel.
Reference
Giri VN, Knudsen KE, Kelly WK, et al. Implementation of germline testing for prostate cancer: Philadelphia Prostate Cancer Consensus Conference 2019 [published online June 9, 2020]. J Clin Oncol. doi: 10.1200/jco.20.00046.
