Long-term risk of metachronous gastric neoplasms after curative endoscopic submucosal dissection for early gastric cancer

Background: There is currently no consensus on long-term risk stratification for metachronous gastric neoplasms (MGNs) occurring beyond 5 years following endoscopic submucosal dissection (ESD).This study aimed to investigate the time-dependent changes in predictive factors for MGN after curative ESD for early gastric cancer (EGC) and analyze the clinicopathological features of late MGNs. Methods: We retrospectively reviewed patients who underwent ESD for early gastric neoplasms between March 2005 and June 2020. MGN was defined as a new gastric neoplasm detected at a different site >12 months following ESD. Survival data were collected and analyzed using multivariable and time-split Cox hazard regression models. Results: Among 5,571 patients treated with ESD, 876 were included with a median follow-up of 58 months. The cumulative incidence of MGN was 10.79% at 5 years and continued to accumulate beyond 5 years (26.65% at 10 years). All MGNs were stage I and there was no gastric cancer-related mortality. Cox regression analysis identified family history of gastric cancer (adjusted hazard ratio [aHR] 2.12, 95% confidence interval [CI] 1.32 – 3.41) and extensive intestinal metaplasia (aHR 6.50, 95% CI 3.73 – 11.36) as independent predictors of MGN. Histological upgrade was not associated with MGN during the first 5 years but emerged as a significant risk factor in the late period (interaction P value = 0.005). Conclusion: MGNs may develop even beyond 5 years following ESD with curative resection in patients with EGC. These findings highlight the long-term risk of MGN after ESD, providing a framework for clinical risk estimation.