Predictors and Patterns of Recurrence After a Watchful Waiting Approach following Clinical Complete Response to Neoadjuvant Radiochemotherapy for Esophageal Cancer.

(1) Background: Treatment of esophageal cancer (EC) traditionally consists of neoadjuvant radiochemotherapy (RCT) followed by resection; however, esophagectomy is associated with substantial morbidity, particularly in patients with relevant comorbidities. Therefore, a watchful waiting (WW) strategy has been increasingly adopted for patients achieving a complete response to RCT. This study aimed to identify independent predictors and recurrence patterns in EC patients managed with WW. (2) Methods: We retrospectively analyzed all patients with potentially curable EC and complete response to RCT treated at a tertiary university hospital between 2014 and 2022. Comprehensive staging and restaging were performed using computed tomography, endoscopy with ultrasound and biopsies, and positron-emission tomography, followed by structured surveillance. Recurrence patterns and associated clinical and tumor-related factors were assessed using multivariate regression analysis. (3) Results: Among 50 included patients, 30 (60%) developed recurrence after a median of 202 days. Patients with initially nodal-negative disease did not develop distant recurrence, whereas nodal-positive patients showed metastatic recurrence in 26% and local regrowth in 16%. (4) Discussion: Adenocarcinoma, circumferential tumor extent greater than 50%, dysphagia, fatigue, and deterioration of general condition at restaging were independently associated with recurrence. These findings support risk-adapted surveillance and may facilitate personalized management in EC patients undergoing WW.