By Mary L. Schmitt, MS, FNP-BC, CNP, AOCNP®, ACGN
Anthony is a 60-year-old patient who was diagnosed with localized prostate cancer at age 59. His family history is positive for prostate cancer, with his father diagnosed at age 69. Following radical prostatectomy surgery, a prostate-specific membrane antigen positron-emission tomography/computed tomography reveals boney metastatic lesions in multiple ribs.
His medical oncologist prescribes abiraterone and prednisone treatment for his stage IV disease. His oncologist also mentions that he is making a referral for genetic counseling and testing and is ordering tumor testing for homologous recombination repair (HRR) and DNA mismatch repair (MMR) genes. The next day, you receive the following questions from the patient in his patient portal: “Why do I need genetic testing? What are HRR and MMR genes?”
What Would You Do?
Indications for germline genetic testing for prostate cancer have been integrated into the medical management of prostate cancer. National Comprehensive Cancer Network guidelines recommend genetic counseling and testing for patients with high-risk, very-high-risk, and metastatic prostate cancer with or without a family history of cancer. Identifying hereditary cancer predisposition through genetic testing may guide treatment decisions, provide prognostic insights, and identify additional cancer susceptibility and family members at risk. See the sidebar for a list of recommended biomarker testing for metastatic prostate cancer.
Cellular DNA damage occurs throughout a person’s lifespan, and the loss of DNA repair is a specific characteristic of cancer. HRR is a DNA repair pathway that is very effective for double-strand DNA damage. Deficiency in one of the many genes associated in this pathway, either inherited (germline) or acquired (somatic), may be a predictive biomarker for effective treatment with PARP inhibitors or may be used to determine a patient’s eligibility for clinical trials. Inherited deficiency (pathogenic variant) in several HRR genes is associated with hereditary risk of prostate cancer.
Deficiencies in one of the genes in the MMR pathway leads to unstable DNA sequences (called microsatellite instability). Acquired deficiency in MMR genes may be predictive for successful treatment with immune checkpoint inhibitors. Inherited deficiency in one of the MMR genes is associated with Lynch syndrome and hereditary risk of several cancers, including prostate cancer.
Oncology nurses can look to the ONS Genomics and Precision Learning Library for quick video resources such as: What Are Key Indicators of Hereditary Risk for Cancer? in the “Glad You Asked” video series or the patient-facing Genetic Counseling and You video for information to use in thoughtful patient discussions about genetic counseling and germline testing.
In everyday clinical practice, oncology nurses can use the ONS Biomarker Database decision support tool to quickly sort by disease type (prostate cancer) and easily find information on biomarkers, targeted therapies, testing modalities and clinical trial opportunities all in one place. The Next-Generation Sequencing Toolkit also contains a comprehensive guide to biomarker testing.
After reviewing those two resources, you meet with Anthony to answer his questions about genetic testing. You explain how the results can help his oncologist personalize his treatment and potentially connect him to clinical trials. You show him the videos and give him links to review them again later. Anthony tells you that he now feels confident and prepared to make decisions about genetic testing for his metastatic prostate cancer.