Tumor response to neoadjuvant treatment as a predictor of benefit for adjuvant treatment in esophago-gastric cancers: a systematic review and meta-analysis

Abstract

Background It is unclear which patients will benefit most from adjuvant chemotherapy for locally advanced esophago-gastric adenocarcinoma after systemic neoadjuvant treatment and resection. This study aims to systematically evaluate the efficacy of adjuvant chemotherapy in patients with resected esophago-gastric adenocarcinoma, based on pathologically documented response (pathological response) to the same neoadjuvant regimen. Materials and methods A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Relevant articles were acquired from PubMed, Embase, Web of Science, and Scopus from 2000 to 2025. Patients were trichotomized into minimal, partial, and complete pathological responders to neoadjuvant chemotherapy based on resection histology. A meta-analysis of overall survival (OS) and recurrence-free survival (RFS) comparing patients who did and did not receive adjuvant chemotherapy was carried out. Results Eleven studies were included in this systematic review, and five were meta-analyzed, totaling 6600 and 4688 patients, respectively. For partial responders, adjuvant chemotherapy conferred a significant RFS [pooled hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.57-0.87] and OS (pooled HR 0.64, 95% CI 0.53-0.77) benefit. Conversely, for complete responders, adjuvant chemotherapy did not confer an RFS (pooled HR 0.57, 95% CI 0.19-1.73) or OS (pooled HR 1.00, 95% CI 0.32-3.08) benefit. In minimal responders, adjuvant chemotherapy was not associated with an RFS [pooled HR 0.64, 95% CI 0.28-1.48] or OS (pooled HR 0.72, 95% CI 0.49-1.05) benefit. Studies that were not eligible for meta-analysis were described qualitatively. Conclusion Pathological response to neoadjuvant chemotherapy may help stratify oncological benefit from subsequent adjuvant chemotherapy, potentially supporting more personalized adjuvant treatment decisions in esophago-gastric cancer.