Background: Progress in understanding molecular changes in advanced prostate cancer has led to promising precision oncology opportunities; to date, most have been concentrated at tertiary research centers and urban centers and unequally available to patients. The VHA is the largest integrated healthcare system in the U.S. and provides medical care to >6 million veterans (~40% living in rural areas). The VHA has implemented a system-wide National Precision Oncology Program (NPOP) to offer tumor NGS testing to veterans with cancer. Methods: VHA patients with advanced stage cancers were offered targeted NGS gene panels (Personalis ACE Extended Cancer Panel; PGDx CancerSELECT/PlasmaSELECT) as part of clinical care. Annotated sequence data is collected by NPOP. We report preliminary findings of the participating veterans with prostate cancer.
Results: 372 veterans from 81 sites underwent NGS sequencing of their prostate tumors (n=311) or cfDNA (n=61). Tumors from 165 (44%) were found to have mutations (allelic ratio ≥5%) in 47 genes. Of 372, 62 harbored mutations in TP53 (17%), 9 in NOTCH1 (2%), 16 in PTEN (4%), 16 in AR (4%), 13 in ATM (4%), 11 in BRCA2 (3%), 2 in MSH2 (0.5%), 1 in NBN (0.3%), and 1 in PALB2 (0.3%). 7 men (1.8%) had adequate tumor, but no identifiable somatic mutations. NPOP findings were compared to the existing databases SU2C/PCF (of metastatic biopsies in metastatic castration resistant disease) and TCGA (of primary tumors in localized disease), see table. Findings will be updated at presentation.
Conclusions: The VA NPOP has been successfully implemented, and prostate tumors from veterans were found to carry potentially actionable mutations, including BRCA2 and ATM, for which there are precision treatment trials. The program will be expanded and will facilitate more diverse and equitable distribution of access to precision oncology diagnostics and therapeutic opportunities, in alignment with the Cancer Moonshot Initiative. (e.g. VA-ABCD clinicaltrials.gov; NCT02985021).
Authors: Alexandra Sokolova, Heather H. Cheng, Bradley J Hintze, Michael J. Kelley, Neil L Spector, Jill Duffy, Julie Ann Lynch, Matthew Rettig, Robert B. Montgomery
Author Affiliations: University of Washington, Seattle, WA; VA National Oncology Program, Durham, NC; Department of Veterans Affairs, Durham, NC; VA Health Care System, Salt Lake City, UT; VA Greater Los Angeles Health Care System, Los Angeles, CA