“Radiofrequency Ablation in Barrett’s Esophagus with Dysplasia”
Shaheen NJ, Sharma P, Overholt BF, et al.
N Engl J Med. 2009;360(22):2277-2288. [Full Text]
Esophageal adenocarcinoma (AC) has a poor prognosis and increasing incidence in the developed world. Most if not all esophageal ACs arise from Barrett’s metaplasia and addressing this precursor was the goal of this study.
But it should be noted that the risk of conversion of Barrett’s dysplasia to AC is quite low and actually lower than initial estimates, which were skewed by publication bias. Early estimates of AC risk from Barrett’s were 1 in 125 person years but are now more likely 1 in 769-860 person years . Additionally, patient’s with detected Barrett’s have the same life expectancy as those without and are very unlikely to die from esophageal AC [1,2].
So while this study addressed the management of dysplastic Barrett’s, once it is found, the still controversial and likely more meaningful clinical question of whom should be screened for Barrett’s has not been addressed by a high quality study (though multiple guidelines make recommendations based on available evidence, i.e. ).
All patients in this study had endoscopically-demonstrated non-nodular, dysplastic Barrett’s esophagus. Participants with high-grade dysplasia were screened for esophageal adenocarcinoma with endoscopic ultrasound prior to the study. Those with history of esophageal cancer, varices, active esophagitis or stricture were excluded. Patients were randomized in a 2:1 ratio into either radiofrequency ablation or sham procedure groups, then stratified based on the degree of their dysplasia and the length of their Barrett’s esophagus. All participants were treated with esomeprazole 40mg bid and underwent a 12-month assessment.
The primary outcome was complete eradication of dysplasia and intestinal metaplasia. Secondary outcomes included progression of dysplasia, the proportion of biopsy samples that were free of intestinal metaplasia at 12 months, patient discomfort and adverse events.
Of the 127 participants in the intention-to-treat population, 63 were classified as having high-grade dysplasia, 42 were then randomized to the ablation group and 21 to the sham group. There were 64 participants with low-grade dysplasia, 42 of which were placed in the ablation group and 22 in the sham group.
In the ablation group, eradication of dysplasia was achieved in 90.5% of patients with low-grade dysplasia, and 81% of the patients with high-grade dysplasia; the overall rate of eradication in the ablation group was 77.4%. In the control group, the primary outcome was achieved in only 2.3% of patients (P<.001). Progression of disease and incidence of esophageal adenocarcinoma was significantly lower in the ablation group, 3.6% vs 16.3% (P=.03) and 1.2% vs 9.3% (P=.045), respectively. Symptoms of chest pain were more common in the ablation group. Also in the ablation group, 6% of patients developed esophageal stricture and one patient experienced upper GI hemorrhage.
This study demonstrates a high rate of reversion to squamous epithelium after radiofrequency ablation and a reduced rate of disease progression and incidence of esophageal cancer in both dysplasia subgroups. While the decreased incidence of cancer in the ablation group is encouraging, it should be noted the study size is relatively small and if only one patient int the ablation group developed AC, the result would not reach statistical significance .
This study also reported a higher incidence of esophageal cancer at 1-year than prior studies, though this was postulated to be a product of the histologic requirement needed the for “high-grade dysplasia” categorization. Two pathologists had to agree on the diagnosis of high-grade dysplasia and this could have excluded borderline cases of high-grade dysplasia and created a more severe group. Lastly, at the time of this study, the long-term success of the eradication was unknown, so further studies looking at the long-term effects were warranted.
Before this trial, high-grade dysplasia in Barrett’s esophagus was being treated with esophagectomy. This study demonstrated an effective, relatively low-risk and minimally invasive solution to what would have otherwise come at the cost of major morbidity and mortality. This intervention is now one of the first-line therapies for any grade of dysplasia (other interventions include photodynamic therapy or spray cryotherapy).
Summary by Chancellor Shu
- Kahrilas PJ. The problems with surveillance of Barrett’s esophagus. N Engl J Med. 2011;365(15):1437-1438. doi:10.1056/NEJMe1108435
- Spechler SJ, Souza RF. Barrett’s esophagus. N Engl J Med. 2014;371(9):836-845. doi:10.1056/NEJMra1314704
- ASGE STANDARDS OF PRACTICE COMMITTEE, Qumseya B, Sultan S, et al. ASGE guideline on screening and surveillance of Barrett’s esophagus. Gastrointest Endosc. 2019;90(3):335-359.e2. doi:10.1016/j.gie.2019.05.012