Background: When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM). Objective: This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC. Methods: This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients. Results: The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p < 0.001) and vascular invasion (HR 4.75; p = 0.014). Moreover, patients with both LNM and vascular invasion had a high rate of recurrence after additional surgery (24.6% in 5 years), with a high HR (119.32) compared with those with neither LNM nor vascular invasion. Among patients with no vascular invasion, a high rate of recurrence was observed in those with N2/N3 disease according to the American Joint Committee on Cancer TNM staging system (27.3% in 5 years), in contrast with no recurrence in those with N1 disease. Conclusions: Patients with both LNM (N1–N3) and vascular invasion, as well as those with N2/N3 disease but no vascular invasion, would be candidates for adjuvant chemotherapy after additional surgery for curability C-2 ESD of EGC.
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