Underrepresentation in GI Cancer Trials Threatens Real-World Applicability

Key Clinical Summary

• Older adults, racial and ethnic minorities, and male patients in certain cancers remain underrepresented in gastrointestinal (GI) cancer randomized clinical trials (RCTs).
• Disparities between RCT participants and real-world populations limit the external validity of GI cancer research.
• Broader inclusion criteria and community-based recruitment are critical to ensure equitable, evidence-based care.

A comprehensive review of US gastrointestinal (GI) cancer randomized clinical trials (RCTs) from 2000 to 2024 reveals persistent demographic inequities in trial participation. The study, published in Journal of Gastrointestinal Oncology, found consistent underrepresentation of older adults, racial and ethnic minorities, and male patients in select cancers—raising concerns about the generalizability of findings to the broader population.

Study Findings

Researchers conducted a retrospective analysis of GI cancer RCTs registered in ClinicalTrials.gov and compared demographic data—age, sex, race, and ethnicity—against real-world Surveillance, Epidemiology, and End Results (SEER) program data. Trials spanning colorectal, pancreatic, gastric, hepatic, esophageal, and cholangiocarcinoma (CCA) cancers were included.

Across 1033 trials, marked discrepancies emerged. Older adults (aged >65 years) were consistently underrepresented, especially in colorectal (32% in RCTs vs 56% real-world), hepatic (31% vs 60%), and pancreatic cancers (43% vs 69%). Similarly, male participants were underrepresented in esophageal (64% vs 82%) and hepatic (64% vs 73%) trials despite higher real-world incidence.

Racial and ethnic disparities were particularly striking. White participants were overrepresented across nearly all GI cancer trials, while Black, Asian, and Hispanic patients were underrepresented. For example, Hispanic participants comprised only 10% of pancreatic and 9% of CCA trial populations—less than half their real-world incidence (21% and 13%, respectively). Black participants made up 8% of pancreatic and 8% of CCA trial populations, compared with 15% and 21% in SEER data.

Clinical Implications

The study underscores a growing concern in oncology: that the populations enrolled in RCTs often do not mirror those most affected by cancer. Underrepresentation of older adults is particularly concerning, as they account for the majority of GI cancer cases and may respond differently to therapy due to comorbidities and altered pharmacodynamics.

Racial and ethnic imbalances similarly limit the translation of trial findings into real-world benefit. Genetic and environmental factors influencing cancer biology vary by population, meaning trial results derived from demographically narrow cohorts may fail to predict outcomes in diverse groups.

To address these gaps, the authors urge policy-level and institutional changes—expanding trial access to community settings, relaxing restrictive eligibility criteria, and mandating transparent demographic reporting. Such steps, they note, are vital to advancing precision medicine and ensuring equitable treatment outcomes for all patients with GI cancers.

Conclusion

Significant demographic disparities persist in US GI cancer RCTs, notably among older adults and racial and ethnic minorities. Without intentional reform in trial design and recruitment, the external validity of GI cancer research remains at risk, potentially perpetuating inequities in care and outcomes.

Reference

Ghusn W, Maalouf E, Jawhar N, et al. Disparities in gastrointestinal cancer trials recruitment: analyzing demographic gaps compared to the real-world. J Gastrointest Oncol. 2025;16(5):1962-1970. doi:10.21037/jgo-2025-276