**Background:** Surveillance protocols after curative treatment for esophageal cancer vary widely due to a lack of evidence. With expanding therapeutic options for recurrent disease (immunotherapy, salvage surgery, stereotactic radiotherapy, resection of oligometastatic disease), the optimal follow-up strategy remains unclear. This study aimed to determine the independent impact of intensive surveillance (IS) on survival and health-related quality of life (HRQL) compared with standard surveillance (SS).
**Methods:** The European iNvestigation of SUrveillance after Resection for Esophageal cancer (ENSURE) study was an international multicenter observational cohort study across 20 high-volume centers. IS was defined a priori as annual CT imaging for at least 3 years postoperatively. Data were collected from prospectively maintained databases on consecutive patients undergoing surgery with curative intent for esophageal or esophagogastric junction cancer (2009–2015). The primary outcome was overall survival (OS); secondary outcomes included disease-specific survival (DSS), recurrence patterns, treatment of recurrence, and HRQL (EORTC QLQ-C30 and QLQ-OG25). Multivariable Cox proportional hazards, logistic, and linear regression analyses were performed, adjusting for age, sex, ASA grade, histology, tumor site, margin status, pathologic T and N stage, treatment protocol, operation type, approach, postoperative complications, and center volume.
**Key Results:** A total of 4,682 patients were included (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median follow-up of 60.3 months, 47.5% developed recurrence; 39% had oligometastatic recurrence. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12–0.25]) and increased tumor-directed therapy (OR 2.09 [1.58–2.77]). After adjustment, no OS benefit was observed among all patients (HR 1.01 [0.89–1.13]), but OS was significantly improved with IS for patients treated with surgery alone (HR 0.60 [0.47–0.78]) and those with lower pathological T stage (Tis-2, HR 0.72 [0.58–0.89]). Conversely, IS was associated with reduced OS in patients with locally advanced T stage (T3-4, HR 1.20 [1.03–1.39]) and those receiving neoadjuvant therapy (HR 1.15 [1.00–1.32]). For patients with recurrence, IS showed a trend toward improved DSS (HR 0.88 [0.77–1.01]) and OS (HR 0.89 [0.78–1.01]). Endoscopic surveillance did not improve DSS or OS overall (HR 1.05 [0.90–1.23] and HR 0.99 [0.87–1.13], respectively). Regarding HRQL, IS was associated with greater anxiety (P=0.016) and financial difficulties, but reduced dysphagia scores (P=0.006); no clinically relevant differences in overall HRQL were observed.
**Clinical Implications:** These data suggest that intensive surveillance may benefit selected patients—those with early-stage disease or favorable pathological stage after neoadjuvant therapy—while not improving outcomes and potentially causing harm in patients with locally advanced disease. The findings provide evidence to inform shared decision-making and guideline development, highlighting that surveillance strategies should be tailored to individual patient risk profiles. The authors call for prospective randomized trials and improved harmonization of surveillance protocols across centers.