Survival Differences Among Non-pCR Patients with Distinct Pathological Outcomes After Neoadjuvant Therapy for...

Non-pathological complete response (non-pCR) patients 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 inadequately defined. This study aimed to elucidate their prognostic value and refine postoperative evaluation systems.

This multicenter retrospective cohort study included patients with ESCC from eight high-volume esophagectomy centers in China who underwent neoadjuvant chemoradiotherapy (nCRT) or 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 early versus advanced pathological-stage cohorts. 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 pCR rates to nCRT but achieved more extensive nodal dissection and significantly reduced distant recurrence (P < 0.001). Among pathological subtypes, MPR(+)LN(-) yielded the most favorable long-term outcomes, surpassing or comparable to those of pCR, whereas MPR(-)LN(+) was associated with the worst prognosis (P<0.001). Notably, MPR(+)LN(-) patients had comparable survival between early- and advanced-stage cohorts, suggesting a reduced prognostic impact of pathological stage, underscoring its dominant predictive value.

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