Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.
A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).
Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.
This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Jun 09 [Epub ahead of print]
Veda N Giri, Karen E Knudsen, William K Kelly, Heather H Cheng, Kathleen A Cooney, Michael S Cookson, William Dahut, Scott Weissman, Howard R Soule, Daniel P Petrylak, Adam P Dicker, Saud H AlDubayan, Amanda E Toland, Colin C Pritchard, Curtis A Pettaway, Mary B Daly, James L Mohler, J Kellogg Parsons, Peter R Carroll, Robert Pilarski, Amie Blanco, Ashley Woodson, Alanna Rahm, Mary-Ellen Taplin, Thomas J Polascik, Brian T Helfand, Colette Hyatt, Alicia K Morgans, Felix Feng, Michael Mullane, Jacqueline Powers, Raoul Concepcion, Daniel W Lin, Richard Wender, James Ryan Mark, Anthony Costello, Arthur L Burnett, Oliver Sartor, William B Isaacs, Jianfeng Xu, Jeffrey Weitzel, Gerald L Andriole, Himisha Beltran, Alberto Briganti, Lyndsey Byrne, Anne Calvaresi, Thenappan Chandrasekar, David Y T Chen, Robert B Den, Albert Dobi, E David Crawford, James Eastham, Scott Eggener, Matthew L Freedman, Marc Garnick, Partrick T Gomella, Nathan Handley, Mark D Hurwitz, Joseph Izes, R Jeffrey Karnes, Costas Lallas, Lucia Languino, Stacy Loeb, Ana Maria Lopez, Kevin R Loughlin, Grace Lu-Yao, S Bruce Malkowicz, Mark Mann, Patrick Mille, Martin M Miner, Todd Morgan, Jose Moreno, Lorelei Mucci, Ronald E Myers, Sarah M Nielsen, Brock O'Neil, Wayne Pinover, Peter Pinto, Wendy Poage, Ganesh V Raj, Timothy R Rebbeck, Charles Ryan, Howard Sandler, Matthew Schiewer, E Michael D Scott, Brittany Szymaniak, William Tester, Edouard J Trabulsi, Neha Vapiwala, Evan Y Yu, Charnita Zeigler-Johnson, Leonard G Gomella
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA., Duke University School of Medicine and Duke Cancer Institute, Durham, NC., University of Oklahoma College of Medicine, Norman, OK., Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., National Society of Genetic Counselors, Chicago, IL., Prostate Cancer Foundation, Santa Monica, CA., Yale Cancer Center, New Haven, CT., Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Dana-Farber Cancer Institute, Boston, MA., Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Department of Laboratory Medicine, University of Washington, Seattle, WA., The University of Texas MD Anderson Cancer Center, Houston, TX., Fox Chase Cancer Center, Philadelphia, PA., Roswell Park Comprehensive Cancer Center, Buffalo, NY., Moores UC San Diego Comprehensive Cancer Center, San Diego, CA., Department of Urology, University of California, San Francisco, San Francisco, CA., James Comprehensive Cancer Center and Department of Internal Medicine, The Ohio State University, Columbus, OH., University of California, San Francisco, Cancer Genetics and Prevention Program, San Francisco, CA., Center for Health Research, Genomic Medicine Institute, Geisinger, Danville, PA., Duke University Medical Center, Durham, NC., North Shore University Health System, Evanston, IL., Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Northwestern University, Chicago, IL., Departments of Radiation Oncology, Urology, and Medicine, University of California, San Francisco, San Francisco, CA., Advocate Aurora Health, Milwaukee, WI., University of Pennsylvania, Basser Center for BRCA, Philadelphia, PA., Integra Connect, West Palm Beach, FL., University of Washington, Seattle, WA., American Cancer Society, Atlanta, GA., Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Urology at Royal Melbourne Hospital, North Melbourne, VIC, Australia., Johns Hopkins Medical Institutions, Baltimore, MD., Tulane University, New Orleans, LA., Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD., City of Hope Comprehensive Cancer Center, Duarte, CA., Washington University School of Medicine, St Louis, MO., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., The Ohio State University, Columbus, OH., Henry Jackson Foundation for the Advancement of Military Medicine, Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD., University of California, San Diego, La Jolla, CA., Memorial Sloan Kettering Cancer Center, New York, NY., University of Chicago, Chicago, IL., Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA., National Cancer Institute, National Institutes of Health, Bethesda, MD., Mayo Clinic, Rochester, MN., Department of Urology and Population Health, New York University and Manhattan Veterans Affairs, New York, NY., Harvard Medical School, Boston, MA., University of Pennsylvania, Philadelphia, PA., Brown University, Providence, RI., University of Michigan, Ann Arbor, MI., Midlantic Urology, Phoenixville, PA., Department of Epidemiology, Harvard TH Chan School of Public Health, Boston MA., University of Utah, Huntsman Cancer Institute, Salt Lake City, UT., Abington-Jefferson Hospital, Abington, PA., Prostate Conditions Education Council, Elizabeth, CO., University of Texas Southwestern Medical Center at Dallas, Dallas, TX., University of Minnesota and Masonic Cancer Center, Madison, WI., Cedars-Sinai Medical Center, Los Angeles, CA., Prostate Cancer International, Virginia Beach, VA., Northwestern Medical Group, Urology Department, Chicago, IL., University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA.