Survival differences among patients with nonpathological complete response with distinct pathological outcomes after...

Patients with nonpathological complete response constitute the majority of esophageal squamous cell carcinoma (ESCC) cases after neoadjuvant therapy, yet the prognostic implications of different pathological outcomes-particularly major pathological response (MPR) combined with lymph node (LN) status-remain poorly defined. This study aimed to elucidate their prognostic value and to refine postoperative evaluation systems.

This multicenter retrospective cohort study included patients with ESCC from 8 high-volume esophagectomy centers in China who underwent neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant immunochemotherapy (nICT) followed by R0 resection between 2016 and 2023. The primary comparison was between the nCRT and nICT cohorts, with additional planned analyses of pathological response subgroups and pathological stage cohorts (early vs advanced). Propensity score matching was used to balance baseline characteristics, and survival outcomes were compared using Kaplan-Meier and Cox regression analyses.

After matching, nICT demonstrated similar pathological complete response (pCR) rates to nCRT but achieved more extensive nodal dissection and significantly reduced distant recurrence (P < .001). Among pathological subtypes, MPR(+)LN(-) yielded the most favorable long-term outcomes, surpassing or equaling those of pCR, whereas MPR(-)LN(+) was associated with the worst prognosis (P < .001). Notably, patients with MPR(+)LN(-) had comparable survival between early- and advanced-stage cohorts, suggesting a reduced prognostic impact of pathological stage and underscoring its strong predictive value.

Patients with MPR and LN negativity had long-term survival comparable to pCR, suggesting that multidimensional pathological evaluation may improve prognostic accuracy. Compared with nCRT, nICT demonstrated improved nodal clearance and systemic disease control across different pathological outcomes.