She then showed the slide below showing the relationship between a timeline of gene discoveries, changes in testing capability, and the evolution of precision medicine applications within prostate cancer.
She went on to discuss the relationship between DNA repair alterations and specific prostate cancer therapies, which are predicated on the synthetic lethality between specific defects in homologous recombination repair of DNA and PARP inhibition. The pivotal clinical trials of PARP inhibitors in prostate cancer are summarized below.
The role of germline testing in the decision to pursue active surveillance for patients with low-risk prostate cancer is evolving. Dr. Giri highlighted a publication1 showing that patients with BRCA2 as well as BRCA1/2 and ATM alterations were more likely to have pathologic upgrading on subsequent prostate biopsy. Whether this implies if patients with BRCA1, BRCA2, or ATM mutations should not undergo active surveillance is unclear.
The discussion then shifted to the current NCCN guidelines for germline genetic testing in prostate cancer patients. These are summarized below. Many options for germline genetic testing exist, from guideline-based small panels of 5-6 genes to comprehensive panels consisting of up to 80 genes. Prior to undergoing prostate cancer genetic screening, informed consent is critical to setting expectations for potential implications of results. This counseling must include a description of the purpose of germline testing, the risk of uncovering hereditary cancer syndromes, the differences in potential testing panels, potential out of pocket costs, laws against genetic discrimination, the possibility of uncovering cancer risk that leads to cascade testing of relatives, and potential implications for therapy.
Multiple clinical trials across the spectrum of prostate cancer are incorporating genetic testing in various ways. These are discussed in more detail in the other educational sessions.
Presented by: Veda N. Giri, MD, Associate Professor and Director of the Clinical Cancer Genetics Service, Jefferson Health, Philadelphia, PA
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
References:
- Cartera H., Helfand B., Mamawala M. et al. "Germline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer." European Urology. 2019. 75, 5, 743-749.