Preliminary results from the first prospective study of a genomic classifier for African-American men suggest that both disparities in access to care and biological factors may be responsible for the increased incidence and mortality in this patient population. The study also identified a significant age difference between African-American and non–African-American men with respect to high genomic risk. These findings were presented during the American Society of Clinical Oncology 2021 virtual annual meeting.
“The National Comprehensive Cancer Network [NCCN] risk categories may be suboptimal in assessing true disease burden in a subset of African-American men who are likely to have a high genomic risk for distant metastasis,” said the study’s lead investigator, Kosj Yamoah, MD, PhD, Director, Radiation Oncology Health Disparities Research, Moffitt Cancer Center, Tampa, FL. “Therefore, integration of the genomic classifier into clinical features to appropriately stage and risk-stratify African-American men to guide treatment recommendations will constitute an important step towards addressing disparities in prostate cancer.”
According to Dr Yamoah, African-American men have a higher incidence of prostate cancer and are more likely to die from the disease compared with their white counterparts. However, prostate-specific outcomes are identical between race groups only if there is timely diagnosis, appropriate staging, and the delivery of adequate and equitable treatment.
“Emerging data suggests that a subset of African-American men may harbor genomic features consistent with aggressive prostate cancer,” said Dr Yamoah. “Disease stratification by the standard clinical risk groupings for staging and treatment are suboptimal as they do not capture underlying tumor biology and genomic diversity of prostate cancer.”
The Decipher genomic risk classifier offers robust information on prostate cancer aggressiveness and has been validated in multiple patient cohorts, but its validation as an optimal genomic classifier for African-American men is lacking in a prospective trial, Dr Yamoah reported.
Study Design
The multisite VanDAAM study enrolled 218 African-American and non–African-American patients with low- or intermediate-risk prostate cancer and similar characteristics such as age, prostate-specific antigen level, and Gleason score. 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.
All patients underwent whole-transcriptome profiling to determine their Decipher genomic classifier score, which can predict risk for prostate cancer metastasis. Patients’ risk for distant metastatic disease was also determined by current NCCN guidelines using prostate-specific antigen levels and Gleason score.
African Americans More Likely to Be Reclassified to High Genomic Risk
According to Dr Yamoah, preliminary results showed age to be the only standout variable between races, with a significant difference in age persisting between African-American men and non–African-American men with respect to high genomic risk. The median age for African-American men was 61 years versus 67 years for the non–African-American cohort.
“We observed a significant difference in age for men who were clinically classified with early localized disease and yet had high genomic risk for metastatic disease within 5 years,” he said. “This finding points to an underlining discrepancy in age at diagnosis for African-American men, which may speak to the overall risk for development of prostate cancer in men of African origin. This could also have implications in screening guidelines.”
In addition, a race-stratified comparison of NCCN and genomic risk groupings showed that low- and favorable-risk African Americans were more likely to be reclassified as high genomic risk for distant metastasis compared with non–African Americans.
“Among non–African-Americans with clinically low-risk disease, we found no patients who were high genomic risk,” Dr Yamoah said. “In the African-American cohort, however, 20% of clinically low-risk patients were found to have high genomic risk for metastatic disease within 5 years, and this number was even higher for favorable-risk patients.”
According to a risk deviation model developed by the investigators, which incorporated both clinical and genomic features, up to 27% of African Americans experienced an extreme deviation of risk status.
As Dr Yamoah explained, patients with low risk and intermediate risk per NCCN guidelines are often treated as having very localized disease and are sometimes placed on active surveillance without considering the genomic factors that can impact disease progression. The discrepancy in NCCN risk classification versus genomic risk assessment among African Americans could thus explain the inferior outcomes observed in subsets of this patient population.
“The genomic classifier outperforms clinical risk stratification tools in African-American men and should be used independent of race to prognosticate patients and tailor treatments accordingly,” Dr Yamoah concluded.
