Topic: NGLC-Genomics-Need-to-Know

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem, Director of the Personalized Prostate Program, and Director of Clinical Research in the Program for Personalized Cancer Care, discusses germline genetic testing and its ability to support prostate cancer (PCa) diagnosis and prognosis when used effectively. He begins with the NCCN guidelines for PCa germline testing, detailing its recommended use for patients with: intermediate-risk, high-risk, regional or metastatic disease; intraductal histology; Ashkenazi Jewish ancestry; family history (FH) of high-risk germline mutations; and positive family history of cancer. Dr. Helfand then considers genetic assessments, stressing the importance of FH, rare pathogenic mutations (RPMs), and SNPs in reaching conclusions. He continues with an explanation of genetic risk score (GRS), a number calculated based on the cumulative variation across multiple SNPs which is then used to provide an estimate of disease risk, and shows data supporting the idea that GRS is more informative than FH. He looks at how to complete genetic testing with intention, suggesting screening with the goal of identifying men at risk of PCa and aggressive cancer, as well as identifying men who are likely to respond to specific chemotherapies. Dr. Helfand also reviews data from the UK biobank showing the associations FH, RPMs, and GRS have with PCa incidence and mortality. He also presents data on active surveillance showing that it should be used with caution if patients have any DNA damage repair genes. Dr. Helfand reviews data on DNA damage response and cancer therapy, showing that men with DNA double repair gene mutations are more responsive to PARP inhibitors and platinum-based chemo, while men with mismatch mutations are more responsive to immune checkpoint inhibitors. Dr. Helfand concludes by saying that genetic testing should be included in PCa decision-making more often and used to understand the future of PCa patients.