Recurrence Risk Based on Pathologic Stage After Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma: Implications for Risk-Based Postoperative Surveillance Strategies

Background: This study aimed to investigate the association between pathologic stage and recurrence risk and survival for patients with esophageal squamous cell carcinoma (SCC) after neoadjuvant chemoradiotherapy (CRT). Methods: This retrospective analysis consisted of two patient cohorts who had esophageal SCC treated with neoadjuvant CRT and esophagectomy at two major academic institutions between 2002 and 2015. The study included 174 patients in the training cohort and 51 patients in the validation cohort. Recurrence pattern, frequency, and survival according to pathologic stage were analyzed. Results: After surgery, patients in the training cohort had the following pathologic categories: stage 0 (44.8%, n = 78), stage 1 (6.9%, n = 12), stage 2 (35.6%, n = 62), and stage 3 (12.6%, n = 22). During a median follow-up period of 53.9 months, recurrences developed in 59 patients. The recurrence rates were 22.2% for stages 0 and 1, 38.7% for stage 2, and 68.2% for stage 3 (stages 0 and 1 vs. stage 2 [P = 0.028], stages 0 and 1 vs. stage 3 [P < 0.001], and stage 2 vs. stage 3 [P = 0.017]). More than 20% of patients with stages 0 and 1 or 2 disease experienced late relapses after 3 years of follow-up evaluation, whereas all the patients with pathologic stage 3 had recurrences within 2 years. The 5-year recurrence-free survival rate was 74.7% for the patients with pathologic stage 0 or 1, 61.4% for those with stage 2, and 20.9% for those with stage 3 disease (P < 0.001). These major findings were successfully reproduced in the Western validation cohort. Conclusions: Patients with a higher pathologic stage were associated with a significantly higher risk of recurrences and worse survival. Multicenter and prospective validation is warranted.