Researchers have uncovered differences in the genomic makeup of metastatic prostate cancer cells among U.S. veterans that may be associated with race and ethnicity. These findings will be presented by Valle et al at the 2024 ASCO Annual Meeting (Abstract 5017). The research could translate into opportunities to offer precision-based therapy in these patients.
Background
Black men may have a higher incidence rate of prostate cancer and are often more likely to be diagnosed at a younger age with more aggressive disease compared with White men. The American Cancer Society reported that Black men have a 70% to 110% higher likelihood of developing prostate cancer in their lifetimes and are twice as likely to die from the disease. However, investigating the genomic landscape of prostate cancer in diverse populations may uncover valuable insights into the biological mechanisms underlying the disease in different populations, improve diagnostic and treatment strategies, and contribute to more equitable health outcomes.
Study Methods and Results
In the new study, the researchers used the large next-generation sequencing data set from the Veterans Affairs (VA) National Precision Oncology Program to analyze the affected genes and alteration frequencies in 5,015 U.S. veterans with metastatic prostate cancer who self-identified as non-Hispanic Black (n = 1,784) and non-Hispanic White (n = 3,231). They evaluated the spectrum and frequency of the genetic alterations associated with race and ethnicity as well as whether or not these alterations were linked to survival following cancer diagnosis.
Although they discovered that a similar set of cancer-related genes were altered in both non-Hispanic Black and non-Hispanic White veterans, the frequencies that these alterations were observed at varied significantly between the two groups. After adjusting for individual patient-level factors—including the type of cancer tissue tested, clinical variables, and social determinants of health indices—they found that non-Hispanic Black veterans exhibited higher rates of genomic alterations in immunotherapy targets.
The researchers then examined how these alterations impacted survival and revealed that alterations in tumor suppressor genes like TP53 were associated with lower survival in both non-Hispanic Black and non-Hispanic White veterans—which was consistent with previous reports.
Conclusions
“One of the highlights of our analysis is the prevalence of clinically actionable alterations that are affecting a significant proportion of [patients], regardless of race. This means we may be able to use specific medications that target vulnerabilities in tumors associated with the genomic changes we observed,” emphasized lead study author Luca Valle, MD, Assistant Professor of Radiation Oncology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), a member of the UCLA Health Jonsson Comprehensive Cancer Center, and a staff physician at the Greater Los Angeles VA Healthcare System. “Ensuring equal access to genomic tumor testing and precision medicine treatments may be a viable strategy to help close the well-described gaps in prostate cancer outcomes between Black and White men. This work really emphasizes the fact that equal access [to] health-care systems such as the VA Healthcare System enables precision-guided therapies, which may result in more equitable outcomes in men with advanced prostate cancer,” he continued.
The new findings illuminated an critical step forward in understanding the landscape of genomic alterations in metastatic prostate cancer, which is especially significant for Black men who have historically experienced poor representation in precision oncology studies. The researchers stressed a critical need for personalized approaches to improve prostate cancer treatment.
“Overall, this study really reinforces the importance of precision medicine initiatives for men with advanced prostate cancer. By integrating tumor genomic information into patient selection for metastatic prostate cancer treatments or clinical trials, health-care providers can strive to improve treatment outcomes for all patients, irrespective of race or ethnicity,” concluded Dr. Valle.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
