Survival and Pathologic Response After Neoadjuvant Treatment in Esophagogastric Cancer

Background: Esophagogastric cancer (EGC), encompassing oesophageal, gastroesophageal junction (GEJ), and proximal gastric malignancies, remains a major contributor to global cancer mortality. Neoadjuvant therapy, chemotherapy (CT) or chemoradiotherapy (CRT) is now standard for locally advanced, resectable disease. However, variability in treatment response and survival outcomes continues to challenge therapeutic optimisation. Methods: This systematic review followed the PRISMA 2020 guidelines and included studies published between January 2020 and September 2025. Eligible studies enrolled adult patients with resectable EGC treated with neoadjuvant CT or CRT, reporting data on pathological response (pathological complete response (pCR) or tumour regression grade (TRG)) and survival outcomes [overall survival (OS), disease-free survival (DFS)]. Sixty studies (18 randomised controlled trials and 42 cohort analyses) were included for qualitative synthesis. Results: Across all regimens, pCR rates ranged from 8% to 49%, with CRT achieving higher pCR (mean 33%) and major TRG response (63%) compared to CT alone (pCR 22%, TRG 48%). Immunotherapy-enhanced protocols (IO-CRT and IO-CT) demonstrated the most promising outcomes, reaching mean pCR rates up to 48–50%. Patients with complete or major regression consistently achieved superior OS and DFS, confirming pathological response as a consistent prognostic marker for long-term survival. Significant clinical heterogeneity was observed across histological subtypes (SCC vs. AC), treatment intensity, and surgical timing, while methodological heterogeneity stemmed from variations in TRG systems, follow-up duration, and reporting standards. Conclusions: Pathological response is consistently associated with survival following neoadjuvant therapy in EGC, yet its predictive power is modulated by tumour histology and treatment modality. Standardisation of TRG assessment, integration of molecular biomarkers, and harmonisation of study design are essential for improving comparability and advancing personalised, multimodal strategies in oesophagogastric oncology.