Assessing circulating tumor DNA (ctDNA) in patients with esophageal squamous cell carcinoma (ESCC) identifies high recurrence risk after surgery.

• Pre-neoadjuvant chemotherapy, ctDNA was detected in 100% of advanced stages and 50% of stage I.
• Recurrence rates soared to 77.8% in ctDNA-positive patients versus 27.8% in ctDNA-negative patients, with a hazard ratio of 4.56.

Consider ctDNA status for guiding postoperative surveillance and therapy decisions.

• During follow-up, ctDNA positivity correlated with a recurrence rate of 100% at 2-16 weeks post-surgery compared to 30.4% in ctDNA-negative patients.