Outcomes after radical endoscopic resection of high risk T1 esophageal adenocarcinoma: an international multicenter retrospective cohort study

Abstract

Background

Post-endoscopic resection (ER) management of high risk T1 esophageal adenocarcinoma (EAC) is debated, with conflicting reports on lymph node metastasis (LNM). We aimed to assess outcomes following radical ER for high risk T1 EAC.

Methods

We identified patients who underwent radical ER (tumor-negative deep margin) of high risk T1 EAC, followed by surgery or endoscopic surveillance, between 2008 and 2019 across 11 international centers.

Results

106 patients (86 men; mean [SD] age, 70 [11] years) were included. Of these, 26 (age, 64 [11] years) underwent additional surgery, with residual T1 EAC found in five patients (19%) and LNM in two (8%). After a median [IQR] follow-up of 47 [32–79] months, 2/26 patients (8%) developed LNM/distant metastasis, with one EAC-related death (4%), one unrelated death (4%), and four patients lost to follow-up (15%). Of the 80 patients (age, 71 [9] years) who entered endoscopic surveillance, 5/80 (6%) developed LNM/distant metastasis, with four EAC-related deaths (5%) over 46 (IQR 25–59) months follow-up; there were 15 unrelated deaths (19%), and 10 patients lost to follow-up (13%). The overall rates (95%CI) were: LNM, 6% (2%–12%); LNM/distant metastasis, 7% (3%–13%); EAC-related mortality, 5% (2%–11%); overall mortality, 20% (95%CI 13–29).

Conclusion

Our findings present low rates of LNM after radical ER of high risk T1 EAC, consistent with other endoscopy-focused studies. Post-surgical patients are still at risk for metastasis and disease-specific mortality. These results suggest that endoscopic surveillance is suitable for selected cases, but further prospective studies are needed to refine patient selection and confirm optimal outcomes.

Publication History

Received: 11 May 2024

Accepted after revision: 12 February 2025

Accepted Manuscript online:
13 February 2025

Article published online:
28 April 2025

• References

• 1 Bailey SH, Bull DA, Harpole DH. et al. Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg 2003; 75: 217-222
• 2 Markar SR, Karthikesalingam A, Thrumurthy S. et al. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000–2011. J Gastrointest Surg 2012; 16: 1055-1063
• 3 Raymond DP, Seder CW, Wright CD. et al. Predictors of major morbidity or mortality after resection for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. Ann Thorac Surg 2016; 102: 207-214
• 4 Manner H, Wetzka J, May A. et al. Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2–3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns. Dis Esophagus 2017; 30: 1-11
• 5 Yoshida M, Takizawa K, Nonaka S. et al. Conventional versus traction-assisted endoscopic submucosal dissection for large esophageal cancers: a multicenter, randomized controlled trial (with video). Gastrointest Endosc 2020; 91: 55-65 e52
• 6 Chan MW, Nieuwenhuis EA, Pouw RE. Today's mistakes and tomorrow's wisdom... in the management of T1b Barrett's adenocarcinoma. Visc Med 2022; 38: 196-202
• 7 Weusten B, Bisschops R, Coron E. et al. Endoscopic management of Barrett's esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2017; 49: 191-198
• 8 Obermannova R, Alsina M, Cervantes A. et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33: 992-1004
• 9 Sharma P, Shaheen NJ, Katzka D. et al. AGA Clinical Practice Update on endoscopic treatment of Barrett's esophagus with dysplasia and/or early cancer: Expert Review. Gastroenterology 2020; 158: 760-769
• 10 Manner H, May A, Pech O. et al. Early Barrett's carcinoma with "low-risk" submucosal invasion: long-term results of endoscopic resection with a curative intent. Am J Gastroenterol 2008; 103: 2589-2597
• 11 Scholvinck D, Kunzli H, Meijer S. et al. Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease. Surg Endosc 2016; 30: 4102-4113
• 12 Gotink AW, van de Ven SEM, Ten Kate FJC. et al. Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study. Endoscopy 2022; 54: 109-117
• 13 Nieuwenhuis EA, van Munster SN, Meijer SL. et al. Analysis of metastases rates during follow-up after endoscopic resection of early "high-risk" esophageal adenocarcinoma. Gastrointest Endosc 2022; 96: 237-247 e233
• 14 Graham D, Sever N, Magee C. et al. Risk of lymph node metastases in patients with T1b oesophageal adenocarcinoma: A retrospective single centre experience. World J Gastroenterol 2018; 24: 4698-4707
• 15 Benech N, O'Brien JM, Barret M. et al. Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low-risk tumours are not associated with lymph node metastases. United European Gastroenterol J 2021; 9: 362-369
• 16 Doumbe-Mandengue P, Beuvon F, Belle A. et al. Outcomes of endoscopic submucosal dissection for early esophageal and gastric cardia adenocarcinomas. Clin Res Hepatol Gastroenterol 2021; 45
• 17 Sobin LH, Gospodarowicz MK, Wittekind C. , ed. TNM Classification of Malignant Tumours; UICC. Oxford: Wiley Blackwell; 2009
• 18 Westerterp M, Koppert LB, Buskens CJ. et al. Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction. Virchows Arch 2005; 446: 497-504
• 19 Molena D, Schlottmann F, Boys JA. et al. Esophagectomy following endoscopic resection of submucosal esophageal cancer: a highly curative procedure even with nodal metastases. J Gastrointest Surg 2017; 21: 62-67
• 20 Otaki F, Ma GK, Krigel A. et al. Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study. Gastrointest Endosc 2020; 92: 31-39 e31
• 21 Alvarez Herrero L, Pouw RE, van Vilsteren FG. et al. Risk of lymph node metastasis associated with deeper invasion by early adenocarcinoma of the esophagus and cardia: study based on endoscopic resection specimens. Endoscopy 2010; 42: 1030-1036
• 22 Pech O, May A, Manner H. et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 2014; 146: 652-660 e651
• 23 Manner H, Pech O, Heldmann Y. et al. The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns. Surg Endosc 2015; 29: 1888-1896
• 24 Kunzli HT, Belghazi K, Pouw RE. et al. Endoscopic management and follow-up of patients with a submucosal esophageal adenocarcinoma. United European Gastroenterol J 2018; 6: 669-677
• 25 Weusten B, Bisschops R, Dinis-Ribeiro M. et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2023; 55: 1124-1146