Clinical outcomes after endoscopic management of low-risk and high-risk T1a esophageal adenocarcinoma: A multicenter study

Background: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC including intraluminal EAC recurrence, extra-esophageal metastases, and overall survival. Methods: Patients who underwent EET for T1a EAC at 3 referral BE endotherapy units between 1996-2022 were included. Patients with submucosal invasion, positive deep margins, or metastases present at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or LVI, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. Results: 188 T1a EAC patients were included (high-risk, n=45; low-risk, n=143) with median age of 70 years and 84% men. Groups were comparable with respect to age, sex, BE length, lesion size, and EET technique. Rates of delayed extra-esophageal metastases (11.1% vs. 1.4%) were significantly higher in the high-risk group (p=0.02). There was no significant difference in the rates of intraluminal EAC recurrence (p=0.79) and overall survival (p=0.73) between the two groups. Conclusion: High-risk T1a EAC patients undergoing successful EET had a substantially higher rate of extra-esophageal metastases compared to low-risk T1a EAC on long term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.