Oncologic Safety and Recurrence Patterns of Watchful Waiting After Neoadjuvant Therapy for Esophageal Cancer

Abstract Background Esophagectomy remains a cornerstone of curative treatment for esophageal cancer but is associated with substantial morbidity and mortality, particularly in elderly and comorbid patients. As an alternative, watchful waiting (WW)—omitting surgery in patients with a clinical complete response after neoadjuvant therapy and reserving esophagectomy for recurrence—has gained increasing attention. However, WW carries the risk of missing a curative window and allowing progression to metastatic disease, making careful patient selection essential. Aims To analyze recurrence patterns in patients managed with a WW strategy. Methods We retrospectively analyzed all patients undergoing curative-intent treatment for esophageal cancer at our institution between 2014 and 2022. Follow-up data were reviewed until 2025 to ensure a minimum follow-up of at least two years for all patients. Results Among 458 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy, 50 patients were managed with a WW approach. Of these, 8 patients (16%) initially presented with local tumor regrowth without lymph node involvement, while 39 patients (79%) had evidence of regional lymph node involvement. Overall, 30 patients (60%) developed disease recurrence during follow-up. Of these, 15 patients (50%) experienced local or regional recurrence that remained potentially amenable to curative treatment, 10 patients (33%) developed distant metastatic disease, and 5 patients (17%) declined further diagnostic evaluation. Notably, patients with initially localized tumor regrowth without lymph node involvement did not develop distant metastases (Figure 1). Conclusion These findings suggest that a watchful waiting strategy may be safe in carefully selected patients without regional lymph node involvement, for whom follow-up can primarily focus on endoscopic surveillance. In contrast, patients with regional disease may still be considered for WW; however, follow-up should be intensified and include regular imaging to enable early detection of distant metastases.Figure 1:Patterns of recurrence in patients managed with a watchful waiting strategyFor image description, please refer to the figure legend and surrounding text.