The Precision Oncology Program for Cancer of the Prostate (POPCaP) Network: A Veterans Affairs/Prostate Cancer Foundation Collaboration

VA Office of Research and Development

With support from the VA Office of Research and Development, there are research efforts focused on the development of data analytics to identify veterans with metastatic prostate cancer within the electronic health record to ensure access to appropriate testing, treatment, and clinical trials. This will optimize tracking and continuous quality improvement in precision oncology. The Office of Research and Development also supports the use of artificial intelligence to identify predictive markers for diagnosis, prognosis, therapeutic response and patient stratification. POPCaP investigators, along with other investigators from across the VA, conduct research that continually improves the care of veterans with prostate cancer. POPCaP has a special focus on prostate cancer among African Americans, who are disproportionately affected by the disease and well represented in VA. The efforts of the working groups, the research studies and the network as a whole also serve to recruit both junior and senior investigators to the VA in order to support the VA research enterprise.

Active collaborations between the network and other elements of VA include efforts to optimize germline testing and genetic counseling in prostate cancer through the Genomic Medicine Service, which provides telehealth genetic counseling throughout the VA. POPCaP pilots innovative approaches to increase access to clinical genetics and genetic counseling services to support the volume of genetic testing of veterans with cancer. Current National Comprehensive Cancer Network (NCCN) guidelines recommend germline testing for all men with metastatic prostate cancer, which can efficiently identify the roughly 10% of veterans with metastatic disease who carry a germline alteration and provide them with access to studies, FDA-approved treatments, while also offering critical health care information to family members who may also carry a pathogenic germline alteration.

Million Veteran Program

The Million Veteran Program (MVP) has collected > 825,000 germline DNA samples from an anticipated enrollment of > 1 million veterans in one of the most ambitious genetic research efforts to correlate how germline DNA interacts with lifestyle, medications and military exposure to affect health and illness (www.research.va.gov/mvp). MVP is a racially and ethnically diverse veteran cohort that is roughly 20% African American and 7% Hispanic. More than 40,000 of the participants have had prostate cancer, one third of whom are African Americans, giving researchers unprecedented ability to discover factors that impact the development and treatment of the disease in this population. In particular, MVP will provide unique insights into the genetic mutations that drive the development of aggressive prostate cancer in all male veterans, including African Americans. These discoveries will undoubtedly lead to improved screening of and treatment for prostate cancer.

In order to demonstrate clinical utility as well as the infrastructure needs to scale up within the VHA, MVP has launched a pilot project that offers to return clinically actionable genetic results to MVP participants with metastatic prostate cancer, opening the door to new therapies to improve the length and quality of these veterans’ lives. Importantly, the pilot includes cascade testing in family members of enrolled veterans. Given that the original MVP consent did not allow for return of results, and MVP genetic testing is research grade, veterans who volunteer will provide a second consent and undergo clinical genetic testing to confirm the variants. Results from this pilot study also will inform expansion of VA precision oncology efforts for patients with other cancers such as breast cancer or ovarian cancer, where the specific genetic mutations are known to play a role, (eg, BRCA2). In addition, through an interagency agreement with the US Department of Energy (DOE), MVP is leveraging DOE expertise and high-performance computing capabilities to identify clinical and genetic risk factors for prostate cancer that will progress to metastatic disease.

This active research collaboration between POPCaP, MVP, and the Genomic Medicine Service will identify germline BRCA alterations from MVP participants with metastatic prostate cancer and give them access to therapies that may provide better outcomes and access to genetic testing for their family members.