Preoperative circulating tumor DNA (ctDNA) testing can significantly improve risk stratification for patients with early-stage esophageal squamous cell carcinoma (ESCC).

• CtDNA detected in 48.6% of patients; higher prevalence in t2n0 (57.8%) vs t1b (20%).
• Positive ctDNA results correlate with worse recurrence-free survival (RFS) and overall survival (OS) — hazard ratios of 4.15 and 4.02, respectively.
• In t2n0 patients, ctDNA has a 100% positive predictive value for occult nodal metastasis, outperforming standard guidelines.

Integrating ctDNA may refine surgical decision-making and personalize treatment strategies for ESCC patients.