Abstract
BACKGROUND: Circulating tumor DNA (ctDNA) monitoring shows promise for detecting minimal residual disease (MRD) and predicting prognosis in various cancers, but its role in esophageal cancer (EC) post-esophagectomy is unclear. This study evaluated ctDNA for detecting MRD and predicting outcomes in EC patients. METHODS: A two-step observational study included 40 EC patients (36 squamous cell carcinoma and 4 adenocarcinoma) undergoing upfront surgery or neoadjuvant chemotherapy (NAC) followed by esophagectomy. Plasma samples (n = 124) were collected at six time points, and ctDNA was assessed by next-generation sequencing using an in-house cancer panel. Associations with clinical outcomes were analyzed. RESULTS: Pre-therapy ctDNA levels correlated with tumor stage (P = 0.01). Changes in ctDNA levels predicted tumor progression with an area under the curve of 0.77. Postsurgical ctDNA positivity predicted recurrence earlier than radiographic evidence (median: 90 days) and was associated with shorter recurrence-free survival (RFS) and progression-free survival (PFS) across all patients (RFS hazard ratio [HR]: 11.1, P = 0.006; PFS HR: 12.6, P = 0.002). CONCLUSIONS: ctDNA assessment is a reliable tool for detecting MRD and predicting outcomes in EC patients after esophagectomy. This approach provides earlier indications of recurrence and can guide personalized postoperative management.