Study shows value of precision-based approaches in prostate cancer

A recent study published in JAMA Network Open found differences in genomic alteration frequencies between non-Hispanic Black and non-Hispanic White veterans with metastatic prostate cancer, but showed similar survival outcomes between both groups.¹

Isla Garraway, MD, PhD

“This research reinforces that we must not let historical disparities define modern care,” said co-senior author Isla P. Garraway, MD, PhD, director of research in the urology department at the University of California, Los Angeles Health, in a news release on the findings.² “Instead, by prioritizing access to genomic tools, we can drive meaningful change in how prostate cancer is treated across all populations.”

In total, the study included 5015 veterans with metastatic prostate cancer who underwent next-generation sequencing (NGS). Of those, 1784 patients (35.6%) were non-Hispanic Black, and 3231 patients (64.4%) were non-Hispanic White.

According to the authors, “Non-Hispanic Black veterans were younger, had higher prostate-specific antigen levels at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared with non-Hispanic White veterans.”

Data showed that 9 of the 10 most commonly altered genes were the same among both cohorts. However, the frequencies of alterations differed among non-Hispanic Black and non-Hispanic White patients.

For example, non-Hispanic Black patients demonstrated higher odds of having genomic alterations in SPOP (OR, 1.7; 95% CI, 1.2 to 2.6; P = .006). They also showed higher odds of harboring genomic alterations in immunotherapy targets (OR, 1.7; 95% CI, 1.1 to 2.5; P = .02), including high microsatellite instability status (OR, 3.1; 95% CI, 1.1 to 9.4; P = .03).

Conversely, non-Hispanic White patients showed greater odds of harboring alterations in the AKT/PI3K pathway (P < .001), androgen receptor (AR) signaling axis genes (P < .001), DNA repair genes (P < .001), prostate cancer-specific PARPi targets (P = .03), and tumor suppressor genes (P < .001).

According to the authors, the increased odds of harboring alterations in AR signaling among non-Hispanic White patients “may contribute to decreased responsiveness to AR signaling inhibitors in non-Hispanic White compared with non-Hispanic Black patients.”

On multivariate analysis adjusting for patient and tumor-related characteristics, non-Hispanic Black patients continued to show lower odds of harboring genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4 to 0.7; P < .001), AR axis (OR, 0.7; 95% CI, 0.5 to 0.9; P < .001), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5 to 0.8; P < .001).

Kosj Yamoah, MD, PhD

“These results affirm that precision oncology can be a powerful tool for achieving equitable cancer care,” said co-senior author Kosj Yamoah, MD, PhD, chair of the radiation oncology Program at Moffitt Cancer Center, in the news release.² “By using genomic testing to guide therapy selection, we can match patients to treatments based on their tumor biology, not race.”

The investigators then correlated these alterations with survival outcomes. In both non-Hispanic Black and non-Hispanic White patients, alterations in tumor suppressor genes such as TP53 were correlated with shorter overall survival (non-Hispanic Black, HR, 1.54; 95% CI, 1.13 to 2.11; and non-Hispanic White, HR, 1.52; 95% CI, 1.25 to 1.85).

The hazard for death in non-Hispanic White patients was also elevated with immunotherapy targets driven by MMR deficiency and microsatellite high status (HR, 1.44; 95% CI, 1.02 to 2.02) and androgen receptor axis alterations (HR, 1.28; 95% CI, 1.05 to 1.56). In non-Hispanic Black patients, CDK12 alterations also increased the hazard for death (HR, 1.54; 95% CI, 1.13 to 2.11).

Kara Maxwell, MD, PhD

The investigators did not find any genomic alterations or biomarkers that should be excluded from testing based on race.

Co-senior author Kara Maxwell, MD, PhD, an assistant professor of medicine at the University of Pennsylvania’s Perelman School of Medicine, concluded in the news release, “This study shows that when we remove barriers to care and apply precision medicine equitably, we can improve outcomes for all patients.”²

REFERENCES

1. Valle LF, Li J, Desai H, et al. Somatic tumor next-generation sequencing in US veterans with metastatic prostate cancer. JAMA Netw Open. 2025;8(5):e259119. doi:10.1001/jamanetworkopen.2025.9119

2. Largest genomic study of veterans with metastatic prostate cancer reveals critical insights for precision medicine. News release. Moffitt Cancer Center. May 16, 2025. Accessed May 19, 2025. https://www.newswise.com/articles/largest-genomic-study-of-veterans-with-metastatic-prostate-cancer-reveals-critical-insights-for-precision-medicine