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

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.