Endoscopic resection or radical gastrectomy? Risk factors for lymph node metastasis in early gastric cancer: a systematic review and meta-analysis

BACKGROUND: The management of EGC hinges on accurate LNM risk assessment, guiding the critical choice between endoscopic resection (ER) and radical gastrectomy. This study provides a comprehensive evidence synthesis to optimize treatment selection. METHODS: This systematic review and meta-analysis (PROSPERO CRD420251152013) was conducted in accordance with PRISMA guidelines. A comprehensive literature search of PubMed, Web of Science, Scopus, and Embase was performed for studies published up to September 5, 2025. Study quality and risk of bias were assessed using the ROBINS-I tool, and the certainty of evidence for each association was evaluated with the GRADE framework. Statistical heterogeneity was investigated, and the sources were explored through meta-regression where appropriate. RESULTS: One hundred one studies were included. Meta-analysis identified predictors: LVI (OR = 9.04, with LVI negative as reference, 95% CI: 7.18-11.37), mucosal invasion (T1a) (OR = 0.20, with T1b as reference, 95% CI: 0.19-0.22), tumor size ≤ 2 cm (OR = 0.39, with > 2 cm as reference, 95% CI: 0.36-0.43), differentiated histology (OR = 0.45, with undifferentiated type as reference, 95% CI: 0.40-0.50), PNI (OR = 3.41, with PNI negative as reference, 95% CI: 2.46-4.71), ulceration (OR = 1.68, with ulceration negative as reference, 95% CI: 1.37-2.05), age ≤ 60 years (OR = 1.13, with > 60 years old as reference, 95% CI: 1.06-1.21), male (OR = 0.69, with females as reference, 95% CI: 0.65-0.72), middle location (OR = 0.96, with other parts as reference, 95% CI: 0.90-1.02), CEA > 0.5 ng/mL (OR = 1.35, with CEA ≤ 0.5ng/mL as reference, 95% CI: 1.04-1.75), CA199 > 37 U/mL (OR = 4.02, with CA199 ≤ 37 U/mL as reference, 95% CI: 1.46-11.11), CA125 (OR = 1.17, with CA125 ≤ 35 U/mL as reference, 95% CI: 0.48-2.81), CA724 (OR = 1.33, with CA724 ≤ 7 U/mL as reference, 95% CI: 0.84-2.11). All reported pooled ORs represent unadjusted estimates derived from univariate data. CONCLUSION: This meta-analysis provides a comprehensive evidence base for risk stratification in EGC. By distinguishing patients suitable for ER from those requiring radical operation, our findings serve as a critical guide for optimizing clinical practice and resolving the therapeutic dilemma between endoscopy and radical surgery.