Circulating tumor DNA for minimal residual disease detection in esophageal and gastroesophageal junction cancer: from technology to prognosis and treatment guidance

Esophageal and gastroesophageal junction (GEJ) cancers carry high postoperative recurrence rates, driven largely by minimal residual disease (MRD) that conventional imaging and tissue biopsy cannot reliably detect. Circulating tumor DNA (ctDNA) offers a noninvasive, highly sensitive, and dynamically trackable liquid biopsy tool that has substantially advanced MRD detection in solid tumors. This review systematically evaluates the biological properties of ctDNA, critically assesses the strengths and limitations of mainstream detection platforms—including digital PCR, next-generation sequencing, methylation profiling, and multi-omic assays—and consolidates the consistent prognostic evidence linking ctDNA positivity to postoperative recurrence risk, treatment response, and survival outcomes in esophageal and GEJ cancer. We also examine the emerging but investigational role of ctDNA in guiding personalized targeted therapy, immunotherapy, and adjuvant treatment decisions. Key translational barriers remain, particularly the lack of pre-analytical and bioinformatic standardization, false-positive signals from clonal hematopoiesis, and the absence of large-scale prospective interventional validation. Looking forward, we argue that harmonized end-to-end workflows, prospective multicenter trials, multi-omic integration, and AI-assisted analytics will be essential to realize the clinical utility of ctDNA-MRD testing, ultimately supporting its standardized implementation in precision oncology and full-cycle patient care for these malignancies.