The ‘Timing Paradox’ of Esophageal Carcinoma Surveillance: Favorable Biology Requires Longer Follow-Up

Abstract Background Prolonged postoperative follow-up among patients who underwent esophagectomy for esophageal carcinoma is a challenge in both clinical and public health terms. Most institutions adopt scheduled imaging and endoscopic exams for a minimum of five years. Recommendations regarding timing of surveillance are not well-defined and limited evidence exists regarding the role of stage, histology or response to treatment in tailoring follow-up. We sought to describe timing of recurrence accounting for tumor biology and additional clinico-pathological variables. Methods Data from a prospective database of patients undergoing esophagectomy from 2012 to 2023 at a single high-volume institution were retrospectively analyzed. Patients with esophageal adenocarcinoma (AC) and squamous cell carcinoma (SqCC) who underwent margin-negative resection (R0) with a curative intent were included. Results Overall, 312 patients were included. Neoadjuvant treatment was administered to 223 (76%) patients, of whom 67 (23%) had pathologic complete response (pCR). Median follow-up was 25 months and 106 (34%) patients recurred, all within 5 years from surgery. DFS at 3-, 5- years was 59%, 57% (Fig. 1A). Patients who underwent upfront surgery or who had pCR after neoadjuvant treatment had longer DFS than patients with residual disease (p 0.001, Fig. 1B). On univariate regression patients with poorly cohesive tumors (p = 0.019), residual disease (p 0.001), lymphovascular (p 0.001), and perineural invasion (p 0.001) had shorter DFS and recurred entirely within 3 years (Fig. 1D). Conclusion Besides a few exceptions, the near totality of patients recurred within 3 years from esophagectomy, supporting shorter surveillance strategies. Paradoxically, patients with early disease and favorable biological features experienced later recurrences and might benefit from prolonged follow-up. In the era of immune therapy, a multicentric research effort is required to establish consensus on a tailored approach to post-esophagectomy surveillance.