Rethinking evidence generation in gastrointestinal cancer treatment research: the need for both high-quality...

The current research ecosystem on gastrointestinal (GI) cancers-including anal, colorectal, esogastric, pancreatic, hepatocellular, and biliary tract cancers-relies heavily on randomized controlled trials (RCTs), which involve high costs and limited transportability.

Fewer than 10% of therapeutic recommendations for pancreatic adenocarcinoma are based on high-level evidence, a proportion that has not improved between 2011 and 2022. Furthermore, substantial research waste undermines interventional research in GI cancer: 30-37% of completed GI cancer trials lack publicly available results, and only 59% of gastric cancer trials are published as full-text articles. Such waste in research negatively impacts evidence synthesis and guidelines recommendations. While interventional research is the only way to assess the efficacy of a new drug, observational studies and real-world evidence (RWE), using health records, cohorts, registries and/or administrative databases, may offer complementary insights, especially for research questions that cannot be studied by RCTs. In particular, RWE can evaluate treatments in elderly or comorbid patients often excluded from trials, inform decisions for rare tumors such as digestive neuroendocrine neoplasms, and evaluate real-world effectiveness of treatments such as targeted therapies or immunotherapy. While historically RWE reliability was often criticized for biases and data quality issues, methodological advances, such as target trial emulation and data standardization, have enhanced its validity, and it is now increasingly used to support regulatory decisions by agencies like the Food and Drug Administration and the European Medicines Agency.

Better integration of high quality interventional and observational approaches is essential in GI cancer research. Guidance on when to use interventional versus observational studies, depending on the clinical question, may help put this integration into practice. This synergy could reduce research waste, accelerate evidence generation, and help identify more effective personalized treatments for GI cancer patients.