Proposal of New ypStage Grouping System for Patients With Esophageal Squamous Cell Carcinoma Who Underwent Neoadjuvant Chemoradiotherapy Followed by Surgery

Objective: To propose a new ypTNM grouping system to address limitations and improve prognostic relevance. Background: The current eighth edition of the American Joint Committee on Cancer (AJCC) ypStage system shows unsatisfactory prognostic relevance in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT), followed by esophagectomy. Methods: The study cohort included 501 patients with ESCC who received nCRT, followed by esophagectomy at the Samsung Medical Center in Korea between 1994 and 2018 (development cohort), and 422 patients treated at Asan Medical Center (validation cohort). Recursive partitioning with a tree-structured regression model was used to develop and validate a new ypStage grouping system. Results: In the new ypStage grouping system, ypStage I include ypT0N0 only, ypStage II includes ypTis–T2N0 or ypT0–T2N1, ypStage III includes ypT3N0–N1, and ypStage IV includes ypT4N0–N1 or ypTanyN2–3. This system adequately addressed the limitations of the existing AJCC classification system, including overlapping and reversal of survival rates. Moreover, the discrimination ability of the new system was higher than that of the existing system [concordance-index (C-index): 61.9%] in the development (C-index: 66.6%) and validation (C-index: 66.0%) cohorts. NRIe was 0.17 (95% CI: 0.09–0.26, P < 0.001) and 0.18 (95% CI: 0.10–0.27, P <0.001) in the development and validation cohorts, respectively. Conclusions: The current study proposes a clear revised version of the eighth edition of the AJCC ypStage grouping system that exhibits superior prognostic stratification in patients with ESCC treated with nCRT, followed by esophagectomy.