Study Finds Genomics, Precision Medicine May Exacerbate Racial Disparities in Prostate Cancer

Racial disparities in health outcomes, including in cancer, are well documented. However, it’s not always clear how biological or socioeconomic factors affect these disparities, or whether advances in genomics and precision medicine have an impact.

Now, new research presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting is painting a clearer picture of what drives differences in mortality and outcomes for patients with prostate cancer, which has higher incidence and mortality among Black men.

The lifetime probability of developing prostate cancer is 18.2% among Black men compared with 13.3% among White men. Black men are also significantly more likely to die of prostate cancer than White men (4.4% vs 2.4%).1

Although the advances in genomics and precision medicine promise to improve risk prediction and outcomes for many cancers, they may actually exacerbate these disparities. In a study presented as an abstract by Foundation Medicine and collaborators, Brandon Mahal, MD, assistant professor of Radiation Oncology and Assistant Director of Community Outreach and Engagement at the Sylvester Comprehensive Cancer Center, and researchers looked at how patterns of comprehensive genomic profiling and treatment varied by race.2

The data, coming from the largest known cohort of its kind, revealed that despite having similar frequency of actionable gene alterations, men of African descent were less likely than men of European ancestry to receive early comprehensive genomic profiling and be enrolled in clinical trials.

The researchers collected data on over 11,000 patients with advanced prostate cancer with comprehensive genomic profiling, including 1400 men of African descent and 9200 patients of European descent. They also analyzed real-world data from nearly 900 patients from Foundation Medicine and Flatiron Health’s clinic-genomic database.

The rates of alterations in BRCA1/2, AR, DNA damage response pathway genes, and actionable genes were similar across the 2 ancestry types. And while both groups were just as likely to receive immunotherapy and PARP inhibitor treatment, men of African descent were nearly 3 times less likely to receive an investigational treatment in a clinical trial compared with men of European descent (11% vs 30%). This remained true even among men with actionable alterations (1% vs 6%).

“Men of African ancestry experience the greatest burden of disease in prostate cancer, and this research indicates that differences in cancer care are not solely based on biological factors, but rather points to socioeconomic factors such as access to comprehensive genomic profiling and clinical trial enrollment,” Mahal said in a statement.3 “To ensure equitable opportunities for precision medicine, we need to expand access to and awareness of advances that impact patient care and outcomes, including timely use of genomic testing to help make informed treatment decisions.”

During a separate presentation, Mahal explained that most genomic studies are based on Eurocentric cohorts, with approximately 80% of patients included in the genome-wise association study (GWAS) being of European descent despite accounting for 16% of the population, leaving the door open to worsening disparities due to a lack of representative studies.4

Mahal outlined several approaches that could be taken to both study and address disparities in prostate cancer, including:

• Transdisciplinary research that bridges basic, clinical, and epidemiological research
• Trials that include diverse populations
• Precision medicine used as a means to identify mechanisms of disparity
• Outreach program to bring care delivery and cutting-edge science to diverse communities.

References

1. Cancer Facts & Figures for African Americans 2016-2018. American Cancer Society website. Accessed June 18, 2021. https://www.cancer.org/research/cancer-facts-statistics/cancer-facts-figures-for-african-americans.html

2.Sivakumar S, Lee J, Moore J, et al. Ancestral characterization of the genomic landscape, comprehensive genomic prostate cancer: A large-scale analysis. J Clin Oncol. 2021;39(Suppl 15): abstr 5003. doi:10.1200/JCO.2021.39.15_suppl.5003

3. New study results presented by Foundation Medicine and collaborators at ASCO21 on cancer care underscore importance of equitable access to precision medicine advances. News release. Foundation Medicine; June 4, 2021. Accessed June 6, 2021. https://www.foundationmedicine.com/press-releases/aa904bd1-4854-44e9-8d03-24b5af5ff392.

4. Martin AR, Kanai M, Kamatani Y, et al. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Gen. 2019;51(4):584-591.