Genomic profiling, treatment patterns are associated with disparities in prostate cancer outcomes

Comprehensive genomic profiling (CGP) utilization patterns and treatment patterns may play a larger role in advanced prostate cancer disparities than genomics, according to data published in the Lancet Digital Health.1,2

Data showed that the prevalence of alterations in AR and DNA damage response pathways were similar among men of different ancestries.

“I believe this is the largest and most representative genomic study of advanced prostate cancer in men of African and European ancestry. The data clearly show no notable differences in genetic mutations between the ancestries that we would target for treatment, which suggests these mutations probably are not driving disparities in advanced prostate cancer,” said senior author Brandon Mahal, MD, in a news release on the findings.2 Mahal is an assistant professor of radiation oncology at the University of Miami Sylvester Comprehensive Cancer Center in Miami, Florida.

For the study, investigators evaluated biopsies from 11,741 men with advanced prostate cancer to determine the prevalence of gene alterations across ancestries. Clinical and treatment information from 1234 patients were also retrospectively reviewed to determine real-world treatment patterns and overall survival.

Data showed that the prevalence of alterations in AR (P = .32) and DNA damage response pathways (P > .05) were similar among men of different ancestries. Alterations in other actionable genes were also similar, with prevalence rates of 22.4% among men of European ancestry, 22.1% among men of African ancestry, and 23.8% among men of East Asian ancestry (P > .05).

The investigators also found no significant differences in real-world overall survival for metastatic castration-resistant prostate cancer among men of different ancestries.

The findings did, however, reveal differences in treatment patterns. Men of African ancestry were less likely to receive CGP early in their treatment course, having received a median of 2 lines of therapy before CGP compared with European men, who received a median of 1 line of therapy (P = .029). Patients who received fewer than 2 lines of therapy were found to have an improved overall survival (median of 22 months) compared with patients who received more than 2 lines of therapy before CGP (13 months).

Men of African ancestry were also less likely to be treated on clinical trials after undergoing CGP, with only 10% of patients of African ancestry receiving a clinical study drug after CGP compared with 26% of men of European ancestry (P = .0005). More specifically, only 5% of men of African ancestry received a clinical study drug as their first line of therapy after CGP compared with 14% of men with European ancestry (P = .033).

Despite these findings, Mahal suggested that the role of genomics in prostate cancer risk should still be considered.

“While this study looked at advanced prostate cancer and diminished the focus on genomics as the reason for disparities, there is still a reason to study the role of genomics in men’s risk for developing prostate cancer,” he concluded in the news release.

References

1. Sivakumar S, Lee JK, Moore JA, et al. Comprehensive genomic profiling and treatment patterns across ancestries in advanced prostate cancer: a large-scale retrospective analysis. Lancet Digit Health. 2023;5(6):e380-e389. doi:10.1016/S2589-7500(23)00053-5.

2. New study by Sylvester investigators indicates treatment patterns, not genetics, drive prostate cancer disparities. News release. University of Miami Health System, Miller School of Medicine. May 24, 2023. Accessed May 31, 2023. https://www.newswise.com/articles/new-study-by-sylvester-investigators-indicates-treatment-patterns-not-genetics-drive-prostate-cancer-disparities?sc=mwhr&xy=10016681