Abstract
BACKGROUND: Gastrointestinal (GI) cancers are a leading cause of morbidity and mortality worldwide, accounting for a substantial portion of cancer incidence and cancer-related deaths. Randomized clinical trials (RCTs) are fundamental to the development of new therapies, as they generate evidence on efficacy and safety. However, concerns persist regarding whether trial populations accurately reflect the demographics of real-world patient populations, including variations by age, sex, race, and ethnicity. Underrepresentation of specific subgroups, such as older adults, racial/ethnic minorities, or those with distinct biological risk factors, can limit the external validity of trial findings and impede equitable treatment outcomes. As global populations become increasingly diverse and the burden of GI cancers continues to rise, identifying and addressing disparities in trial enrollment is essential for advancing precision medicine and ensuring that evidence-based treatments benefit all patients equally. This study aimed to compare the demographic profiles of participants in GI cancer RCTs with real-world data, and identify specific disparities in age, sex, race, and ethnicity that could undermine the generalizability of trial results. METHODS: We performed a retrospective analysis of GI cancer RCTs registered in ClinicalTrials.gov between 2000 and 2024. Trials reporting demographic data on age, sex, race, and ethnicity were included. We categorized these trials based on cancer subtype [colorectal, pancreatic, gastric, hepatic, esophageal, and cholangiocarcinoma (CCA)]. The distribution of demographic variables was compared against real-world incidence data from the Surveillance, Epidemiology, and End Results (SEER) program. Discrepancies were quantified as the difference between trial participant proportions and SEER population estimates to identify under- or over-represented groups. RESULTS: We observed consistent underrepresentation of older adults (>65 years) across multiple GI cancer subtypes, particularly those with higher prevalence in older populations. Male participants were disproportionately low in esophageal and hepatic trials. Racial and ethnic imbalances were most evident in pancreatic, hepatic, and CCA studies, with White participants overrepresented and Black, Asian, and Hispanic populations underrepresented. CONCLUSIONS: Significant demographic disparities persist in GI cancer RCTs, notably for older adults, men in certain subtypes, and racial/ethnic minority groups. These discrepancies threaten the generalizability of clinical trial evidence, potentially perpetuating gaps in care. More inclusive recruitment strategies and trial designs are essential to ensure equitable treatment outcomes for diverse patient populations.