Esophagectomy Versus Active Surveillance After Complete Response in Locally Advanced Esophageal Cancer: Retrospective Analysis

Background/Objectives: Esophageal cancer (EC) remains highly lethal. The standard management of locally advanced disease includes neoadjuvant chemoradiotherapy (nCRT) followed by surgery. However, the role of esophagectomy in patients achieving clinical complete response (cCR) after nCRT remains uncertain. Methods: We conducted a retrospective study at the Davidoff Cancer Center, Rabin Medical Center (2013–2023). Patients with thoracic EC (adenocarcinoma and squamous cell carcinoma) stage cT2–4a, N+, M0 who received nCRT (cisplatin/5-FU or CROSS regimen with 41.4–50.4 Gy) were included. Patients with cCR, defined by negative biopsies, endoscopic ultrasound, and PET-CT, were managed with surgery or surveillance. Survival was analyzed using Kaplan–Meier and Cox regression. Results: Of 252 patients treated with nCRT, 118 achieved cCR. Seventy underwent surgery, with 47% (33 patients) achieving pathological complete response (pCR), and 48 were managed with surveillance. Five-year overall survival (OS) was 48% with surveillance and 49% with surgery; disease-free survival (DFS) was 36% vs. 43%. No significant differences were observed in OS (HR = 0.75, 95% CI 0.47–1.26) or DFS (HR = 0.88, 95% CI 0.55–1.41). In patients ≤70 years, surgery conferred an OS and DFS benefit (HR = 0.44, p = 0.03). No benefit was observed in patients >70 years, where outcomes trended against surgery. On multivariable analysis, older age (p = 0.005) and female sex (p = 0.007) were independent predictors of OS. Conclusions: In younger patients (≤70 years), surgery yielded significant survival benefit, supporting its role as the preferred treatment. In patients >70 years, surveillance produced comparable or superior outcomes, suggesting deferral of surgery may avoid morbidity without compromising survival. Age-specific tailoring of management is essential.