Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial

Cary C Cotton, W Asher Wolf, Bergein F Overholt, Nan Li, Charles J Lightdale, Herbert C Wolfsen, Sarina Pasricha, Kenneth K Wang, Nicholas J Shaheen, AIM Dysplasia Trial Group, Richard E Sampliner, David E Fleischer, Virender K Sharma, Glenn M Eisen, M Brian Fennerty, John G Hunter, Mary P Bronner, John R Goldblum, Ana E Bennett, Hiroshi Mashimo, Richard I Rothstein, Stuart R Gordon, Steven A Edmundowicz, V Raman Muthusamy, Kenneth J Chang, Michael B Kimmey, Stuart J Spechler, Ali A Siddiqui, Rhonda F Souza, Anthony Infantolino, John A Dumot, Gary W Falk, Blair A Jobe, Robert H Hawes, Brenda J Hoffman, Prateek Sharma, Amitabh Chak, Cary C Cotton, W Asher Wolf, Bergein F Overholt, Nan Li, Charles J Lightdale, Herbert C Wolfsen, Sarina Pasricha, Kenneth K Wang, Nicholas J Shaheen, AIM Dysplasia Trial Group, Richard E Sampliner, David E Fleischer, Virender K Sharma, Glenn M Eisen, M Brian Fennerty, John G Hunter, Mary P Bronner, John R Goldblum, Ana E Bennett, Hiroshi Mashimo, Richard I Rothstein, Stuart R Gordon, Steven A Edmundowicz, V Raman Muthusamy, Kenneth J Chang, Michael B Kimmey, Stuart J Spechler, Ali A Siddiqui, Rhonda F Souza, Anthony Infantolino, John A Dumot, Gary W Falk, Blair A Jobe, Robert H Hawes, Brenda J Hoffman, Prateek Sharma, Amitabh Chak

Abstract

Background & aims: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial.

Methods: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence.

Results: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined.

Conclusions: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.

Keywords: HGD; High Grade Dysplasia; LGD; Long-term Outcome; Low Grade Dysplasia; Prognostic Factor.