Comparative Effectiveness and Modality-Dependent Prognostic Value of Pathological Response Following Neoadjuvant...

Neoadjuvant therapies, including chemotherapy (NACT), chemoradiotherapy (NACRT), and chemoimmunotherapy (NACIT), are standard for locally advanced gastric cancer (LAGC). Pathological response is a key surrogate for treatment effectiveness, but its correlation with long-term outcomes across modalities remains unclear.

This retrospective cohort study analyzed 256 LAGC patients receiving neoadjuvant therapy (NACT n = 162; NACRT n = 48; NACIT n = 46) from January 2017 to December 2022. Pathological responses, disease-free survival (DFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox models.

Compared to NACT, NACIT was associated with significantly improved DFS (HR = 0.75, p = 0.035), though no OS difference was observed. Although NACRT enhanced pathological response rates, this was not accompanied by a survival benefit. Crucially, major pathological response (MPR) strongly correlated with improved survival in the NACT and NACIT groups, but no significant association was observed in the NACRT group.

NACIT is associated with improved DFS for patients with LAGC, whereas NACRT suggests a 'pathology-prognosis mismatch,' where improved pathological response may not reliably predict a survival advantage. These findings challenge the uniform application of pathological response as a surrogate endpoint and highlight the critical need for modality-specific interpretation when evaluating neoadjuvant therapy efficacy.