Abstract 688TiP
Background
The prevalence of germline DNA repair gene mutations (gDRm) in men with metastatic prostate cancer (mPC) is >10%. Data suggest that carriers of gDRm have worse prostate cancer (PC) outcomes and that gDRm are enriched in mPC. Thus, gDRm are candidate biomarkers for risk of aggressive PC. To further study these associations, we designed the population-based Genetic Information to Inform Treatment and Screening (GIFTS) Study for Prostate Cancer. Objectives: 1) Recruit men with incident mPC, offer germline genetic testing, and identify gDRm carriers; 2) Identify clinical, pathologic, and molecular features of mPC that distinguish men with gDRm; 3) Develop a stepwise approach for cascade genetic testing of male relatives; and 4) Recruit and follow a cohort of unaffected men with gDRm.
Trial design
This prospective observational study enrolls men ages 35-79y with mPC residing in Washington State (U.S.) identified through the Surveillance, Epidemiology, and End Results (SEER) Program of NCI. Men are contacted by mail and phone and invited to participate. Participants complete brief questionnaires including personal health history and family history of cancer. A saliva collection kit for a CLIA-certified 30-gene targeted panel of cancer predisposition genes (www.color.com) is mailed to participants, who return their sample by mail. Results are issued by phone and/or email. Men with mPC found to have gDRm (index family member) are provided genetic counseling, including discussion about the importance of cascade genetic testing for relatives. Clinical and treatment history of the index man with mPC is collected and tumor material obtained if available. Participants with gDRm and living first-degree male relatives are asked for permission to contact these relatives to invite them to participate in cascade genetic testing through a parallel testing process (free of charge). All male first-degree relatives identified to have gDRm, whether affected or unaffected by PC, will be invited to participate in additional clinical trials, e.g. targeted therapy studies for men with mPC and an early PC detection study for men without PC.
Clinical trial identification
NCT04254133.
Editorial acknowledgement
Legal entity responsible for the study
Fred Hutchinson Cancer Research Center.
Funding
Pacific Northwest Prostate Cancer SPORE CA097186.
Disclosure
All authors have declared no conflicts of interest.