Long-Term Follow-Up After Non-Curative Endoscopic Submucosal Dissection for Early Gastrointestinal Cancer—A Retrospective Multicenter Analysis

<b>Background</b>: Endoscopic Submucosal Dissection (ESD) has become the standard therapy for early malignant lesions in the gastrointestinal tract and has shown as good oncological surgery results. Approximately 30% of ESDs do not meet the criteria for oncological curability, and upfront surgery is indicated. Hence, about 40% of patients with an indication for surgery are advised against surgery because of comorbidities and an advanced age. <b>Methods</b>: We performed a multicenter retrospective cohort study on the long-term outcomes of non-curative ESDs, performed between 2009 and May 2024, without additional tumor therapy. The primary outcome was the recurrence of malignancy, either local malignancy or lymph node metastasis during follow-up, or death. We compared the outcomes between two cohorts: after non-curative ESD (ncESD) and after curative ESD (cESD). <b>Results</b>: A total of 374 ESDs were analyzed in this study. Overall, the technical success rate was 91%, and the oncological curative resection criteria were met in 70.9% of patients. Severe complications occurred in 5% of cases without procedure-associated mortality. In the ncESD group, 20% (7/35) of patients had a recurrence of malignancy primarily due to positive horizontal margins in the resection specimens, and 3 out of 35 died due to a non-oncological reason during the follow-up (mean length 36.6 months). In the cESD group, 3% (1/33) of patients had tumor recurrence, and 1 patient died because of a non-oncological reason. The tumor recurrence rate between the cohorts was significant (<i>p</i> = 0.017), and overall mortality did not show significance (<i>p</i> = 0.33). <b>Conclusions</b>: Especially in the elderly and multimorbid patients, the recommendation to perform rescue surgery after non-curative ESD remains challenging. Residual malignancy rates in surgical resection specimens are low, recurrence rates of malignancy are low, and mortality rates for non-oncological reasons are high in this population. There is a need for more data for the individualization of patient management after non-curative ESD.