After neoadjuvant chemoradiotherapy for esophageal cancer, regrowth predominantly affects the mucosal and submucosal layers, suggesting implications for surgical vigilance.

• In a study of 75 patients with surgical specimens analyzed post-neoadjuvant chemoradiotherapy, 91% had cancer cells in the mucosal layer, and 88% in the submucosa.
• A significant number of patients showed invasive involvement beyond the mucosa, complicating post-treatment surveillance and management.

Surgeons should remain cautious about subtle nodal disease and consider surgery as the primary response to regrowth instead of relying solely on endoscopic evaluation.