Joe Shanks, a medical technician at the San Francisco VA Medical Center, drews a blood sample from Matt Parsons, Air Force veteran, in 2019 at the San Francisco VAMC during enrollment in the Million Veterans Program. VA photo
LOS ANGELES — Prostate cancer affects an estimated 1 in 8 men at some point during their lives, with black men affected at almost double the rate of whites.
While many cases are successfully treated when localized, up to half can metastasize, resulting in significant morbidity and mortality, said Luca Valle, MD, assistant professor in the Department of Radiation Oncology at UCLA and staff physician at the Greater Los Angeles VA Healthcare System. In those cases, genomic profiling—analyzing the genetic mutations in a person’s prostate cancer cells to identify molecular targets for therapy—has shown promise for improving patient outcomes.
Genomic sequencing studies in metastatic prostate cancer have underrepresented Black men, however, despite their higher risk for disease and tendency to experience more aggressive forms of it, Valle noted. With that in mind, a study team involving Valle and his colleagues decided to examine the genetic alteration landscape across a large, racially diverse population of veterans with metastatic prostate cancer.
Leveraging the large next-generation genomic sequencing dataset from the VA National Precision Oncology Program, the researchers analyzed alteration frequencies of specific genes as well as gene groupings in hallmark prostate cancer-related pathways in prostate tumors from 5,015 veterans—1,784 of whom identified their race/ethnicity as non-Hispanic black and 3,231 who self-identified as non-Hispanic white—with metastatic prostate cancer.
The researchers were able to link that genomic data to the clinical data the VA maintains about those same men, said Valle. “[That data included] details about their age, military exposures, social determinants of health variables, and clinicopathologic details from their electronic medical record about their prostate cancer such as the tumor Gleason score, tumor stage, PSA, castrate resistant status, and whether or they had de novo metastatic disease at presentation.” 1
By linking that data, the researchers were able to do a number of sophisticated analyses that allowed them to determine whether there are any significant differences in genomic alteration frequencies and then were able to look at survival to see whether those same alterations impacted survival, Valle said.
“What we found was that there are differences in alteration frequencies between Black and white men,” said Valle, who also presented the findings at the American Society for Clinical Oncology annual meeting in June 2024. For example, after adjusting for a number of patient- and disease-related factors, the authors discovered that Black veterans exhibited higher levels of genomic alterations in immunotherapy targets, a finding that could translate into opportunities to offer precision-based immunotherapies to those men.
The researchers also found that alteration frequencies depended on what type of tissue was tested—primary prostate tissue, metastatic tissue or liquid biopsy (which analyzes cell-free circulating tumor DNA in peripheral blood). Lastly, they found that, for many alterations, survival was actually no different between Black men and white men, which is consistent with other studies evaluating outcomes in the VA health system, he said. Certain alterations like TP53 were associated with worse survival in both Black and white veterans.
“I’m not sure we were surprised by the fact that there are differences in genomic characteristics between Black and white men. Nor were we particularly surprised that survival was similar,” said Valle. “More than anything, this study informs us what the mutational landscape of metastatic prostate cancer looks like in—not just in non-Hispanic white men but in a more diverse sampling of patients. Once you have a sense of the alteration landscape, you can design precision oncology trials that are equitable and relevant to all populations of veterans with metastatic prostate cancer.”
The new study, he said, is a “step in the right direction” toward improving equity—a step that might not have been possible without VA resources. “In the VA we have a unique opportunity to ask questions in diverse cohorts that otherwise would be challenging to answer,” he said. “While genetic testing is recommended for all men with metastatic prostate cancer, they don’t always get it for a number of reasons,” said Valle. “But the VA healthcare system has a number of robust clinical pathways and programs in place to ensure that men actually get the guideline-concordant genetic testing that they need when they are diagnosed with metastatic prostate cancer.”
Overall, the study reinforces the importance of precision medicine initiatives for men with advanced prostate cancer, Valle said. “By integrating tumor genomic information into patient selection for metastatic prostate cancer treatments or clinical trials, healthcare providers can strive to improve treatment outcomes for all patients, irrespective of race or ethnicity.”
- Valle LF, Li J, Desai H, et al. Oncogenic alteration rates, race, and prostate cancer specific mortality in Veterans with metastatic prostate cancer undergoing somatic tumor next generation sequencing. Presented at: 2024 American Society for Clinical Oncology Annual Meeting. May 31-June 4, Chicago, Illinois. Abstract 5017. https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.5017
