Background/Objectives: The current standard of care for T1b/T2 esophageal cancer is esophagectomy. Surgical resection via esophagectomy confers a high risk of morbidity and mortality. Patients who are ineligible for or refuse esophagectomy can receive partial endoscopic removal, plus or minus adjuvant therapies like chemotherapy and/or radiation. The objective of this study was to compare outcomes (overall survival, complications, etc.) among patients with T1b/T2 esophageal cancer undergoing endoscopic resection with adjuvant therapy versus esophagectomy. Methods: Protocol was prospectively registered on PROSPERO. A systematic review of MEDLINE, EMBASE, Scopus, Cochrane Library, and CINAHL was performed according to PRISMA guidelines. Patients with T1b/T2 esophageal cancer undergoing endoscopic resection with adjuvant therapy were included. Summary time-to-event hazard ratios were approximated with the inverse variance method using RevMan. Summary binary outcomes data were analyzed using the Mantel–Haenszel risk ratio. Results: From 10 observational studies included in the quantitative synthesis, 5-year overall survival showed no significant difference between endoscopic resection with adjuvant therapy versus esophagectomy (HR = 1.35; 95% CI = 0.74–2.44, p = 0.33). There were significantly fewer adverse events among patient undergoing endoscopic resection with adjuvant therapy as opposed to esophagectomy (HR = 0.65; 95% CI = 0.44–0.94, p = 0.02). The 5-year disease-free survival and cause-specific survival showed no differences between interventions (HR = 1.12; 95% CI = 0.42–2.96, p = 0.82 and HR = 2.98; 95% CI = 0.73–12.16, p = 0.13, respectively). Conclusions: Endoscopic resection with adjuvant therapy may be a suitable alternative to esophagectomy among patients with T1b/T2 esophageal cancer. Randomized clinical trials are required; there appears to be equipoise, especially in higher-risk patients.
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