[Reflections on surgical management strategies for locally advanced gastric cancer after neoadjuvant immunotherapy].

Abstract

Neoadjuvant immunotherapy is reshaping the treatment landscape of locally advanced gastric cancer (GC). The central clinical challenge has expanded from whether immunotherapy can enhance treatment efficacy to accurate identification of patients who are most likely to benefit and optimization of the subsequent surgical intervention. Accumulating evidence indicates that perioperative immunotherapy-based regimens can improve pathological complete response (pCR) rates and event-free survival (EFS) of the patients, promoting a shift from conventional chemotherapy plus radical surgery toward biomarker-guided, integrated precision treatment. For therapeutic stratification, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) expression, and refined human epidermal growth factor receptor 2 (HER2) classification have emerged as key indicators for predicting treatment response and selecting eligible patients. Meanwhile, treatment response assessment has evolved beyond conventional radiological evaluation to a multimodal framework incorporating pathological assessment, liquid biopsy, endoscopy, functional imaging, and artificial intelligence (AI)-assisted analysis, thereby providing more comprehensive support for individualized therapeutic decision-making. However, improved treatment efficacy has also raised new questions for surgical management. In particular, discordant responses between primary tumors and regional lymph nodes have challenged whether D2 radical gastrectomy planned according to pretreatment clinical staging remains the optimal surgical strategy. This review systematically summarizes the evolution of neoadjuvant treatment strategies for locally advanced GC, comprehensive response assessment, and redefinition of gastrectomy extent and lymphadenectomy strategy. Looking forward, with the clinical translation of emerging therapeutic targets such as Claudin 18.2 (CLDN18.2) and fibroblast growth factor receptor 2 (FGFR2), together with the maturation of AI-driven multimodal assessment systems, GC surgery may move beyond traditional anatomical boundaries. This transition potentially enables "maximally tolerated radical resection" to "function-preserving surgery guided by biological radicality", ultimately providing truly individualized precision surgical treatment for patients with locally advanced GC.