Validation and prognostic stratification limitations of the 8th AJCC ypTNM staging system in esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy: A multicenter retrospective study

The 8th edition of the American Joint Committee on Cancer (AJCC) ypTNM staging system serves as the basis for predicting treatment efficacy, issuing prognostic warnings, and guiding adjuvant therapy in patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. This large‑sample, multicenter study aimed to validate the ypTNM staging system and identify its limitations in prognostic stratification for ESCC after neoadjuvant immunochemotherapy (nICT). Patients who underwent nICT followed by esophagectomy between April 2020 and December 2022 at three national centers were retrospectively enrolled. The prognostic predictive roles of the ypT and ypN categories were analyzed using univariate and multivariate analyses. Based on these findings, the AJCC 8th edition ypTNM staging system was validated and refined. The pathological complete response rate was 28.6% (83/290). The 2-year disease-free survival (DFS) rate and overall survival (OS) rates were 62% and 76%, respectively. Univariate analysis revealed that both the ypT (P = 0.002) and ypN (P < 0.001) categories were significant variables for predicting patient OS. Multivariate analysis confirmed that the ypN stage (P < 0.001) had a stronger prognostic relevance. Notably, patients with pT0N0 did not exhibit superior DFS (P = 0.914) or OS (P = 0.935) compared with those with T1-2N0. Although T0-3N2 and T3N1 are both classified as stage IIIB diseases, the DFS (P = 0.085) and OS (P = 0.062) analyses suggest that these subgroups may require differentiation. Additionally, the AJCC 8th edition ypTNM staging system did not clearly distinguish between stage II and stage IIIA patients, necessitating further subdivisions. Among patients with ESCC who underwent nICT, increasing ypT and ypN categories resulted in a stepwise deterioration in prognosis, with the ypN category demonstrating greater prognostic value. However, no significant survival differences were observed between yp stage II and yp stage IIIA patients, indicating the need for further subgroup refinement.