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

Area of Science:

• Oncology
• Gastroenterology
• Clinical Trials

Background:

• Neoadjuvant therapies are standard for locally advanced gastric cancer (LAGC).
• Pathological response is a key surrogate for treatment effectiveness.
• Correlation between pathological response and long-term outcomes across different neoadjuvant modalities is unclear.

Purpose of the Study:

• To evaluate the correlation between pathological response and long-term survival outcomes.
• To compare the efficacy of neoadjuvant chemotherapy (NACT), chemoradiotherapy (NACRT), and chemoimmunotherapy (NACIT) in LAGC patients.

Main Methods:

• Retrospective cohort study of 256 LAGC patients (2017-2022).
• Patients received NACT (n=162), NACRT (n=48), or NACIT (n=46).
• Evaluated pathological responses, disease-free survival (DFS), and overall survival (OS) using Kaplan-Meier estimates and Cox models.

Main Results:

• NACIT showed significantly improved DFS compared to NACT (HR=0.75, p=0.035), with no OS difference.
• NACRT improved pathological response rates but did not yield a survival benefit.
• Major pathological response (MPR) correlated with improved survival in NACT and NACIT groups, but not in the NACRT group.

Conclusions:

• NACIT is associated with improved DFS in LAGC patients.
• NACRT may exhibit a 'pathology-prognosis mismatch,' where pathological response doesn't guarantee survival advantage.
• Findings challenge uniform use of pathological response as a surrogate endpoint, emphasizing modality-specific interpretation.