Speakers at the 31st Annual Prostate Cancer Foundation (PCF) Scientific Retreat provided updates on the genomics of prostate cancer disparities among individuals of African ancestry.

Following these proceedings, featured expert Neha Vapiwala, MD, FACR, FASTRO, FASCO, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Vapiwala’s clinical perspectives on this topic are presented here.

Black men are disproportionately affected by prostate cancer, with higher incidence rates, earlier presentations, more aggressive disease forms, and higher mortality than other groups. These disparities are generally attributed to genetic/genomic, socioeconomic, and health care access factors. However, the specific causes of disparate outcomes are complex and presumably multifactorial; thus, research on this topic, while interesting and important, can be challenging to conduct and interpret.

For example, race and ethnicity can be studied using different methodologies (eg, African ancestry data vs self-identification vs census), and the extent to which findings from any single study can support more sweeping conclusions is unclear. Additionally, the underrepresentation of Black individuals in clinical trials and genomic databases continues to be a challenge. Competing or conflicting reports in the biomedical literature are also relatively common. For example, one study might report that certain biomarkers are upregulated in Black men with prostate cancer, while a different publication does not observe this finding.

The social determinants of health add yet another layer of complexity, although some trials have attempted to control for these variables. For example, some studies suggest that, despite the differences that may exist between certain epigenetic and genetic profiles, observed outcome disparities still reflect structural and social inequities (eg, access to care, frequency of care, and quality of care). I think that this serves to underscore that biologic and genomic differences alone are not going to explain a given disease state or treatment outcome in every single patient. Sometimes it will be a matter of access to and timeliness of clinical care or the aggressiveness of the selected therapy, whereas, in other cases, it may be predominantly a reflection of underlying tumor biology or differential response to a given treatment based on the individual’s genomic profile.

Putting aside these consequential nonbiological influences, a number of scientific observations have been reported in recent years, including increased AR protein and ligand levels in Black men. Other studies have investigated the AR gene’s CAG repeat length, which appears to vary in a race-specific fashion in men with and without prostate cancer. There are also splice variants that have been implicated in drug resistance among Black individuals (eg, aberrant PIK3CD splice variant). A putative role of vitamin D, involved in cell proliferation, apoptosis, and angiogenesis, as well as immune modulation, has also been noted, with epidemiological work suggesting a connection between vitamin D deficiency and an increased risk of prostate cancer development.

To date, the most common genomic alteration described in prostate cancer involves fusions of the androgen-regulated gene TMPRSS2 to the ERG gene, with deletion and/or mutation of PTEN. Interestingly, this fusion appears to be more common in men of European ancestry than in men of African ancestry. Men of African ancestry generally present with more advanced disease, but their tumors are less likely to acquire TMPRSS2‐ERG. Thus, some ongoing research is exploring the correlation between frequency of these fusions and observed disparities related to the patient’s age and stage at presentation.

At the 31st Annual PCF Scientific Retreat, a session on the genomics of prostate cancer racial disparities was moderated by Vanessa M. Hayes, PhD, from The University of Sydney. Dr Hayes and her team have been working in this area for more than a decade—and, as noted earlier, the genomic data landscape has posed challenges. Of note, Black individuals are underrepresented in oncology databases across all tumor types. Soh et al reported in 2023 on a large, prominent, genome-wide association study in which Europeans contributed 95.85% of the total, whereas African Americans or Afro-Caribbeans contributed only 0.49%. Likewise, enrollment in clinical trials for cancer among Black men is low relative to other demographic groups.

How do we enhance the genomic knowledge base and continue making progress in precision medicine? Certainly, earning the trust of potential study subjects is essential, and we must continue to cultivate strong patient-provider relationships. This is true for all patients, but, given the tragic stories of medical research in relatively recent history, Black individuals have understandably higher rates of distrust of health care providers and clinical research. A recent survey found that Black individuals were 10 times more likely than other groups to say that they had nothing to gain from participating in clinical research. I think that building trust requires a genuine effort to understand the patient’s perspective and ongoing conversations with open, honest communication about the purpose and limitations of the intended research. Investigators and study teams should encourage dialogue to help identify and address potential barriers and concerns that study subjects may have, ensuring that study consent is as informed as possible.