Blood-Based Surveillance Biomarkers for Gastroesophageal Cancers

Gastroesophageal cancers including esophageal and gastric cancer remain major causes of global cancer mortality, primarily due to late diagnosis and high recurrence rates after curative treatment. Current surveillance methods, such as endoscopy and imaging, are invasive, costly, and often inadequate for detection. Blood-based biomarkers ("liquid biopsies") offer a minimally invasive alternative capable of real-time tumor monitoring. In this review, we summarize recent advances across all major classes of blood-derived biomarkers: circulating tumor DNA (ctDNA), methylated DNA, cell-free RNAs (microRNAs, lncRNAs, circRNAs), circulating proteins, autoantibodies, circulating tumor cells, extracellular vesicles, and metabolites. Reviewing the existing literature on gastroesophageal cancers, we highlight current evidence, validation phases, performance metrics, and limitations. Special attention is given to clinical trial evidence, including ctDNA monitoring studies, that demonstrated earlier recurrence detection compared to imaging. While blood-based biomarker analysis has not yet supplanted endoscopy as standard of care in gastroesophageal cancer surveillance, the convergence of multi-analyte assays, AI, and clinical validation trials positions liquid biopsy as a transformative tool in the surveillance of gastroesophageal cancers.