A key recommendation from the 2019 National Comprehensive Cancer Network (NCCN) involves its guidelines on genetic testing and counseling in prostate cancer, in that men with high-risk, extreme high-risk, regional, or metastatic disease should receive genetic testing and counseling. The guidelines also provide more in-depth information regarding family history, making it more clear what history to collect and how to use the information. By understanding this additional background information, oncologists may be able to determine the number of genes that should be assayed for mutations, which may ultimately improve treatment outcomes.
Earlier this year, the NCCN Prostate Cancer Panel reported updated guidelines for genetic testing in prostate cancer during the NCCN Annual Meeting, held March 21 through March 23 in Orlando, Florida. The guidelines highlight a 2016 study evaluating inherited DNA-repair gene mutations in men with metastatic prostate cancer. The results showed no difference in mutation frequency among patients with a family history of prostate cancer and those without. Additionally, men with metastatic disease had a significantly higher frequency of germline mutations in DNA-repair genes than men with localized disease (P <.001). Among the mutations found in all patients, the most common were BRCA2 (44%), ATM (13%), CHEK2 (12%), and BRCA1 (7%), which make patients resistant to certain therapies.
Not Enough Research
When asked about upcoming clinical trials, Mohler explained that “There are many [clinical trials]. There’s one study going on at the National Cancer Institute in the early detection space for people with known BRCA1/2 mutations. There are many clinical trials now that are collecting germline and somatic data as a qualification for entry into the trial and either as a stratification or randomization. Then there is an addition of sequencing in many clinical trials as correlative science, which will inform the development of future clinical trials.”
However, he also stated, “There are so few clinical trials that are acting upon either germline or somatic sequencing results. The ones that are coming along, for the most part, are not yet replicated. It’s difficult to make any kind of definitive statement about how one acts on any of these data at the present time.”
James L. Mohler, MD, stated, “we prescribed what a family history should be, as well as other things that should be captured in addition to diagnoses of prostate cancer. [This may include] other hereditary syndromes, whether they’re Ashkenazi Jewish or not, whether they have known mutations in their families, and of course, whether they’re African American or not. Also, if they have family members with prostate cancer, where are they in the family tree?”
In an interview with Targeted Oncology during the 2019 Prostate Cancer Consensus Conference, Mohler, associate director and senior vice president for translational research, and professor of oncology, Roswell Park Comprehensive Cancer Center, explained the reasons for changes to the NCCN guidelines on genetic testing and counseling in prostate cancer. He also discussed what needs to be addressed in the future to further increase knowledge of genetic testing and improve its use.
In consideration of how he sees prostate cancer and genetic testing changing over the next few years, Mohler said that “Everyone at this meeting [the 2019 Prostate Cancer Consensus Conference] has recognized the importance of genetic counselors, and we’re functioning when we have a deficit in the number of highly trained and highly qualified genetic counselors. There are all kinds of certificate programs now, they are people who can take short courses to try and improve their knowledge so that physicians can do a better job of the pre-genetic testing counseling. As a urologist, I can tell you that I’m woefully inadequate to do this. We need to train more genetic counselors. As urologists, radiation oncologists, and medical oncologists, we also need to become much more knowledgeable in dealing with this rapidly expanding database.”
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