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ASCO Studies Show Impact of Biomarker Testing, Therapy Inequities in Black Men With Prostate Cancer

NEW YORK – Studies presented at the American Society of Clinical Oncology's virtual annual meeting this week illustrated how disparities in access to genomic profiling, treatment, and clinical trials — not just differences in disease biology — are impacting outcomes for Black men diagnosed with prostate cancer in the US.

In one study led by Brandon Mahal, an assistant professor of radiation oncology at the University of Miami's Sylvester Comprehensive Cancer Center, researchers set out to improve understanding of the genomic landscape and outcomes disparities in a large cohort of prostate cancer patients, including men of African ancestry and European ancestry.

Researchers analyzed comprehensive genomic profiling results from 11,741 men, of whom 9,244 were of European descent and 1,422 were of African descent. They found alterations in some genes were enriched among men of African descent that were less prevalent in men of European descent, including SPOP, CDK12, CCND1, KMT2D, HGF, and MYC. The screening also identified alterations in genes that were more common in men of European descent but less prevalent in men of African descent, such as TP53, PTEN, and TMPRSS2-ERG.

However, when it came to genes targetable by treatment, there were similar patterns between men of European descent and of African descent. "There were no significant differences across race in targetable gene alterations in either actionable genes or DNA damage response associated genes, with the exception of BRAF, which was enriched in individuals with African ancestry," Mahal explained.

The team followed a subset of these 11,000 patients further using real-world data collected in Flatiron Health and Foundation Medicine's clinico-genomic database. In this second part of the study, the population shrank significantly to 841 patients, of whom only 79 were of African descent.

In this group, the researchers found differences in the treatment of prostate cancer between racial groups. Men of African descent were less likely to be enrolled in clinical trials with only 11 percent of Black men receiving a clinical study drug compared to 30 percent of men of European descent. The disparity in trial enrollment may be related to where these men were treated. About 9 percent of men with African ancestry received treatment in academic centers compared to 37 percent of men with European ancestry, this study found.

The rate at which prostate cancer patients received an immuno-oncology drug and PARP inhibitors was consistent across racial groups, but men of African descent received a median of two lines of chemotherapy before undergoing comprehensive genomic profiling compared to one line of chemo for men of European descent.

"Intrinsic biological differences are unlikely to be a major driver of ancestry-based disparities among men diagnosed with advanced prostate cancer," Mahal said. "Ultimately, the equitable use of comprehensive genomic profiling, clinical trial enrollment, and subsequent precision medicine treatment pathways could lead to a major reduction in disparities."

While increasing the diversity within clinical trials can diminish racial inequities in healthcare outcomes, it can also ensure that treatments and testing modalities are working similarly across different groups. Kosj Yamoah, director of radiation oncology health disparities research at Moffitt Cancer Center, presented data at the meeting from a prospective study, called VanDAAM, which examined whether Veracyte/Decipher's prostate cancer genomic classifier can predict the risk of metastasis in African American men as accurately as it can for white men.

Researchers enrolled 207 Black patients and non-Black patients with low- or intermediate-risk prostate cancer and similar characteristics like age, PSA level, and Gleason score. Yamoah, the study's lead author, said the enrollment strategy of matching African American and non-African American cohorts by disease characteristics helped the study reach its patient accrual goal and ensure racial groups were evenly distributed.

Patients in the VanDAAM study underwent whole-transcriptome profiling to determine their Decipher genomic classifier score, which can predict the risk of prostate cancer metastasis. Patients' risk of distant metastatic disease was also determined by current National Comprehensive Cancer Network guidelines using PSA levels and Gleason score.

Yamoah and his colleagues found a disparity between the ability of the test and the guidelines to predict Black men's risk of metastasis.

About 20 percent of Black patients who were deemed low risk by the NCCN guidelines were found to have high risk of metastatic disease within five years using the Decipher prostate cancer genomic classifier test. For non-African American patients, there were no patients who were low risk by NCCN guidelines but high risk by the Decipher score.

"Most of the time, low-risk and favorable-risk patients are treated as [having] early-stage, localized disease, and yet we are seeing a high proportion of high genomic risk among the African American cohort," Yamoah said, adding that the NCCN risk categories may be "suboptimal" in assessing disease burden for some African American men.

He noted, however, that just because a test or guideline was developed predominantly in non-Black groups does not mean it won't assess Black men's disease correctly. The Decipher genomic classifier was developed in largely non-African American patients, Yamoah said, yet it performed similarly between Black and white patients in the study.

"Prostate cancer is prostate cancer, and aggressive disease is aggressive disease," he said. "It's not a different type of cancer when we talk about differences in biology. It's enriched biology. It tells us that there is a subset of patients that might have these aggressive phenotypes that we need to pay attention to, and that's probably what drives the disparity [in African American men]. We have both social determinants and enriched biology all factoring into a common disparity."