AUA 2017: Genetic Testing in Inherited Prostate Cancer Risk: Consensus Statement
Dr. Giri elegantly delineated why we need a consensus statement this year, noting the recent studies linking BRCA2 mutation to aggressive PCa and the higher rates of PCa in families with Lynch syndrome as well as the Genome-wide Association Study identifying multiple common variants in prostate-specific-antigen (PSA) risk. PC-multigene panels have certainly focused on BRCA1/2 mutations, and Dr. Giri observed that these specific mutations are now mentioned in the most recent National Comprehensive Cancer Network guidelines. But the questions remain: how do we manage, screen, and test these patients? She indicated that the framework of the consensus statement for genetic evaluation of inherited PC is broken down to referral criteria, genetic counseling, genetic testing, and management.
The criteria for referral for genetic counseling (with excellent consensus agreement) included patients who either have (i) first-degree relatives diagnosed with PC who are 55 years of age or younger, or have a personal diagnosis of PC at age 55 years or younger with a first-degree relative diagnosed with PC at any age or death due to PC in a first-degree relative at 60 years of age or younger; or (ii) two close blood relatives with PC on the same side of the family, with at least one diagnosed at age 55 or younger; or (iii) any first-degree relative with cancer in a hereditary situation (ie, Lynch syndrome) who is diagnosed with PC at 50 years of age or younger; or (iv) tumor sequencing that shows mutations in hereditary cancer genes.
The criteria that should be considered for genetic testing for inherited PC (moderated to excellent consensus agreement) include those with PC who have (i) families with syndromes consistent with hereditary breast, ovarian, or PC or Lynch syndrome; or (ii) men with two or more close blood relatives on the same familial side; or (iii) every man with metastatic castration-resistant PC (67% consensus agreement). Recommendations specific to which genes should be tested included expanding genetic testing to encompass hereditary cancer syndromes (ie, BRCA1/2, HOXB13) or a broader family cancer history and to provide context of relevance of genes based on a family history of disease aggressiveness.
For those who have mutations, the panel developed consensus statements targeting how to screen these patients. For men with a BRCA2 mutation, the consensus was 56% for obtaining a PSA at age 40 or 10 years prior to the youngest PC diagnosis in the family. Furthermore, the interval of screening should be yearly or determined by baseline PSA (76% consensus). For patients with HOXB13 mutation, similar recommendations are made as to men with BRCA2 mutation, which is the first such recommendations for individuals with HOXB13 mutation.
In summary, this is the initial centralized, multidisciplinary consensus to address a working framework toward addressing genetic evaluation for inherited PC. Dr. Giri concluded that “This is a dynamic field that will require updating of the guidelines in the future.”
Presented By: Veda Giri, MD, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA