One-third of patients with locally advanced esophageal cancer show a complete clinical response to neoadjuvant chemoradiotherapy, but managing uncertain responses is critical for surgical success.

• Only 15% of patients with uncertain tumor response achieved a complete pathological response after esophagectomy.
• Complete response rates varied: 26% for non-traversable lesions, 10% for high-grade dysplasia, and 8% for those with clinical suspicion of residual tumor.
• Notably, squamous cell carcinoma patients with non-traversable lesions had the highest complete response rate (33%).

Surgeons should recommend esophagectomy for most patients with uncertain responses, as 85% will have residual disease.