Large-scale analysis reveals distinct genetic patterns in veterans with metastatic prostate cancer

In the largest clinical genomic profiling study of non-Hispanic Black men with metastatic prostate cancer to date, researchers from Moffitt Cancer Center, University of Pennsylvania, University of California Los Angeles and the Veterans Affairs (VA) National Precision Oncology Program found key differences in tumor biology between non-Hispanic Black and non-Hispanic white veterans, but similar survival outcomes when both groups had equal access to care.

The study, published in JAMA Network Open, analyzed data from more than 5,000 U.S. veterans with metastatic prostate cancer who underwent next-generation sequencing between 2019 and 2023. It found that while non-Hispanic Black veterans had higher rates of actionable immunotherapy targets, non-Hispanic white veterans had more frequent alterations in androgen receptor signaling and DNA repair pathways. Despite these biological differences, survival outcomes were comparable in the equal-access VA setting.

“These results affirm that precision oncology can be a powerful tool for achieving equitable cancer care,” said Kosj Yamoah, M.D., Ph.D., senior author and chair of the Radiation Oncology Program at Moffitt. “By using genomic testing to guide therapy selection, we can match patients to treatments based on their tumor biology, not race.”

Dr. Isla Garraway, M.D., Ph.D., co-senior author and director of research in the Urology Department at UCLA Health, emphasized the importance of the study’s implications, “This research reinforces that we must not let historical disparities define modern care. Instead, by prioritizing access to genomic tools, we can drive meaningful change in how prostate cancer is treated across all populations.”

Their key findings include:

• Non-Hispanic Black veterans were significantly more likely to have genomic alterations associated with immunotherapy benefit, such as microsatellite instability.
• Non-Hispanic white veterans had higher rates of mutations in DNA repair genes and the androgen receptor axis, which may influence responsiveness to hormonal therapies.
• Tumor suppressor gene alterations were linked to worse survival in both groups.
• No biomarker was found that should be excluded from testing based on race.

The study’s diverse cohort, consisting of 36% non-Hispanic Black veterans, represents a marked improvement in inclusion compared to previous genomic studies. Researchers emphasized the importance of continuing to broaden access to next-generation sequencing testing and ensuring that underrepresented groups are included in precision oncology research and clinical trials.

“This study shows that when we remove barriers to care and apply precision medicine equitably, we can improve outcomes for all patients,” said Kara Maxwell, M.D., Ph.D., co-senior author and assistant professor of medicine at the University of Pennsylvania’s Perelman School of Medicine.

In the largest clinical genomic profiling study of non-Hispanic Black men with metastatic prostate cancer to date, researchers from Moffitt Cancer Center, University of Pennsylvania, University of California Los Angeles and the Veterans Affairs (VA) National Precision Oncology Program found key differences in tumor biology between non-Hispanic Black and non-Hispanic white veterans, but similar survival outcomes when both groups had equal access to care.

The study, published in JAMA Network Open, analyzed data from more than 5,000 U.S. veterans with metastatic prostate cancer who underwent next-generation sequencing between 2019 and 2023. It found that while non-Hispanic Black veterans had higher rates of actionable immunotherapy targets, non-Hispanic white veterans had more frequent alterations in androgen receptor signaling and DNA repair pathways. Despite these biological differences, survival outcomes were comparable in the equal-access VA setting.

“These results affirm that precision oncology can be a powerful tool for achieving equitable cancer care,” said Kosj Yamoah, M.D., Ph.D., senior author and chair of the Radiation Oncology Program at Moffitt. “By using genomic testing to guide therapy selection, we can match patients to treatments based on their tumor biology, not race.”

Dr. Isla Garraway, M.D., Ph.D., co-senior author and director of research in the Urology Department at UCLA Health, emphasized the importance of the study’s implications, “This research reinforces that we must not let historical disparities define modern care. Instead, by prioritizing access to genomic tools, we can drive meaningful change in how prostate cancer is treated across all populations.”

Their key findings include:

• Non-Hispanic Black veterans were significantly more likely to have genomic alterations associated with immunotherapy benefit, such as microsatellite instability.
• Non-Hispanic white veterans had higher rates of mutations in DNA repair genes and the androgen receptor axis, which may influence responsiveness to hormonal therapies.
• Tumor suppressor gene alterations were linked to worse survival in both groups.
• No biomarker was found that should be excluded from testing based on race.

The study’s diverse cohort, consisting of 36% non-Hispanic Black veterans, represents a marked improvement in inclusion compared to previous genomic studies. Researchers emphasized the importance of continuing to broaden access to next-generation sequencing testing and ensuring that underrepresented groups are included in precision oncology research and clinical trials.

“This study shows that when we remove barriers to care and apply precision medicine equitably, we can improve outcomes for all patients,” said Kara Maxwell, M.D., Ph.D., co-senior author and assistant professor of medicine at the University of Pennsylvania’s Perelman School of Medicine.