Durability of radiofrequency ablation for treatment of esophageal squamous cell neoplasia: 5-year follow-up of a treated cohort in China

Abstract

Background and aims: Radiofrequency ablation (RFA) is an accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study we aimed to evaluate longer term outcomes after RFA for ESCN.

Methods: Patients with flat unstained lesions (USLs) on Lugol's endoscopy containing moderate-/high-grade intraepithelial neoplasia (MGIN/HGIN) or mucosal cancer were treated with RFA every 3 months until complete remission (CR; no MGIN or a worse histologic grade). Patients with CR at 12 months (CR12) were included for follow-up and underwent annual Lugol's endoscopy with biopsy sampling and re-RFA for flat USLs. The clinical course of patients with persistent ESCN at 12 months (treatment failures) is also reported.

Results: Among the 78 patients in CR12, 67 (86%) had sustained CR during a median of 48 months (interquartile range, 48-48) of follow-up and 5 endoscopies (interquartile range, 4-6). Recurrence occurred in 7 of 78 patients (9%; MGIN, n = 6; HGIN, n = 1); all lesions were managed with RFA. Four other patients (5%) had progression (to HGIN, n = 1; submucosal esophageal squamous cell carcinoma, n = 3). During follow-up protocol violations occurred in 46 of 78 patients (59%). Of the 12 treatment failures, progression occurred in 6. Overall, 2 patients developed subepithelial disease that was not visible after Lugol's endoscopy. Based on post-hoc analysis, the pink-color sign at baseline (a pink color change after Lugol's endoscopy) significantly predicted failure after RFA.

Conclusions: RFA is relatively easy to apply and can efficiently treat large areas with ESCN. Despite protocol violations that may have interfered with the efficacy of RFA in 59% of patients, most patients with CR12 had sustained CR during follow-up. However, some patients progressed to advanced disease and 2 developed subepithelial disease, not visible after Lugol's endoscopy. Based on currently available data, we advise the restriction of the use of RFA for flat MGIN and HGIN without the pink-color sign on Lugol's chromoendoscopy. (Clinical trial registration number: NCT02047305.).

Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. A patient with a pink-color sign after Lugol’s staining.

(A) White light endoscopy image without visible abnormalities. (B) Directly after Lugol’s a large unstained lesion appeared from 3 to 7 o’clock and more proximally from 10 to 12 o’clock. Several minutes after application of Lugol’s, the entire USL turned pink (C).

Figure 2.. Patient flow during the full 5 years of treatment and follow-up.

Abbreviations: CR - Complete response, defined as absence of MGIN or worse; CR12 - CR at 12 months endpoint of the original study; ESCC - esophageal squamous cell carcinoma; ESCC-sm — Submucosal esophageal squamous cell carcinoma; FU - follow-up; HGIN - High Grade Intraepithelial Neoplasia; IQR – Interquartile range; LTFU - Lost to follow-up; MGIN - Moderate Grade Intraepithelial Neoplasia; mo - months; RFA – RadioFrequency ablation therapy.

Figure 3.. Kaplan Meijer Curve for durability of ESCN eradication after RFA

Black curve (grey zone representing 95% confidence interval) shows the durability of CR12 after RFA for MGIN, HGIN and early ESCN during the extended follow-up. Eleven patients with recurrent or progressive disease were considered to be failures, even if CR was re-established after Radiofrequency Ablation.

Figure 4.. A recurrent USL during follow-up was successfully retreated with RFA.

At baseline, the patient had a large USL after Lugol’s, extending from 3 to 11 o’clock (A), with HGIN histology, which was treated with circumferential RFA (B). At 12 months patient was in complete remission with absence of USLs after Lugol’s (C) and negative biopsies. One year later, a recurrent USL was found (D), with MGIN histology. The patient was re-treated with a single session of focal RFA (E), and during subsequent follow-up endoscopies through 60 months, the patient re-achieved and sustained a complete remission (F).

Figure 5.

Post-RFA development of submucosal ESCC under normal squamous epithelium