Thanks in large part to the kinds of genetic and precision medicine that the Prostate Cancer Foundation has been funding, the National Comprehensive Cancer Network (NCCN) has issued updated prostate cancer guidelines that include new information about the role of family history and genomic testing to select precision medicine treatments and to determine if cancer risk genes may have been inherited.
New Guidelines for Genomic Testing
PCF-funded studies have found that 20-30% of metastatic castrate resistant prostate cancers (mCRPC) have mutations in DNA repair genes that may make them sensitive to treatment with PARP-inhibitors or platinum chemotherapy.
The new NCCN guidelines recognize the importance of these findings by including updated language recommending consideration of testing mCRPC patients for germline (inherited) and somatic (tumor) mutations in DNA repair genes (BRCA1, BRCA2, ATM, PALB2, FANCA), and referring patients who have these mutations for genetic counseling. At present, this information may be used to refer mCRPC patients with DNA repair gene mutations “for early use of platinum chemotherapy, or eligibility for clinical trials (e.g., PARP-inhibitors),” stated the guidelines.
PCF-funded research has also found that inherited DNA repair gene mutations are present in ~12% of men with metastatic prostate cancer and ~6% of men with localized high risk prostate cancer. Based on these findings, the NCCN guidelines now state that germline genetic testing for these genes and genetic counseling should be considered for all men with high risk, very high risk, regional, or metastatic prostate cancer.
The NCCN guidelines also now include consideration of patients with regionally progressive and metastatic prostate cancer to be tested for microsatellite instability (MSI) and somatic and germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Pembrolizumab has recently been FDA approved for the treatment of solid tumors with these alterations, and could be considered for patients who have already progressed on at least one line of systemic therapy for mCRPC. Patients with germline mutations in these genes should undergo genetic counseling to assess the possibility of familial Lynch syndrome.
What Does this Mean for Men and for Prostate Cancer Patients?
If you have a family history of prostate cancer and other cancers, talk to your family to gather as many details as you can about family history then talk to your doctor about getting genetic counseling and germline genetic testing. Remember, men with a family history should be screened for prostate cancer earlier than those men who have no family history.
There are federal GINA laws prohibiting discrimination due to genetic conditions for health insurance and employment. In some cases, knowing about certain mutations may improve insurance coverage of specific preventative and screening services for you and/or your family members. There are occasions when results could potentially influence life insurance (although genetic results may also not change coverage if you have a family history of cancer). If you would like to review these implications in detail, talking with a genetic counselor prior to testing is strongly recommended.
Finally, new clinical trials are underway and in development to examine additional screening methods with the goal of catching prostate cancer early, and other trials to more effectively treat prostate cancers that arise in men with certain gene mutations to improve chances of cure. Knowing about your genetic risk early can allow you to be more proactive about your health.
PCF’s Role in these Changes
PCF was an early-adopter in funding research to ferret out which genes were responsible for some of the toughest forms of prostate cancer. The result? We’re beginning to see amazing responses to therapy from men who were otherwise without hope. Stories like those of Mark Meerschart and Chris Seeley.
Other Updates in the NCCN Guidelines
The new NCCN guidelines contain numerous updates and clarifications. A few other notable changes include division of the intermediate-risk group into two categories with different guidelines: favorable and unfavorable intermediate risk. The NCCN has added consideration of abiraterone/prednisone combined with ADT for the treatment of men with regional or distant metastatic hormone-naïve prostate cancer, a treatment strategy that recently received FDA approval. New PET-based imaging technologies have also been added to the guidelines to determine the presence of metastatic disease.
About NCCN and Its Guidelines
The National Comprehensive Cancer Network is a not-for-profit alliance of 27 leading cancer centers. NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The panel of experts that contributed to these prostate cancer NCCN guidelines include many PCF-funded investigators.