Ablation Beats Surveillance for Barrett Esophagus and Low-Grade Dysplasia

By Megan Brooks

March 27, 2014

NEW YORK (Reuters Health) - Endoscopic ablation was superior to endoscopic surveillance for Barrett esophagus with low-grade dysplasia, in a multicenter randomized trial.

Compared with surveillance, ablation substantially cut the rate of progression to high-grade dysplasia and adenocarcinoma over three years follow-up. Due to the clear superiority of ablation, the trial was halted early.

"A young and fit Barrett patient with a confirmed diagnosis of low-grade dysplasia has his esophagus waiting for developing cancer and should therefore undergo ablation therapy," Dr. Jacques J. Bergman, from Academic Medical Center Amsterdam, who worked on the study, told Reuters Health by email.

Radiofrequency ablation is standard of care for high-grade dysplasia, as well as residual Barrett tissue after endoscopic resection of early cancer, the study team notes in JAMA March 26.

Yet no trial has ever evaluated the effect of radiofrequency ablation on risk of neoplastic progression in Barrett patients with low-grade dysplasia, until now. Most guidelines advise endoscopic surveillance every six to 12 months in these patients, the researchers say. But that should change given their results, they say.

In the study, 136 patients with a confirmed diagnosis of Barrett esophagus and low-grade dysplasia were randomly assigned to ablative therapy (five sessions maximum) or endoscopic surveillance. There were 68 patients in each group. The study was conducted at nine European centers between June 2007 and June 2011, with follow-up until May 2013.

The researchers found that ablation reduced the risk of neoplastic progression to high-grade dysplasia or cancer over three years (the primary outcome) from 26.5% to 1.5% (p<0.001).

"An absolute risk reduction of 25% in progression means that only four patients need to be treated to avoid one patient from progressing to high-grade dysplasia or cancer," Dr. Bergman said. "This reduction in progression rate already became apparent during a three-year follow-up period; extending the duration of follow-up likely would increase this difference more," he added.

Ablative therapy also reduced the risk of progression to adenocarcinoma from 8.8% to 1.5%, an absolute risk reduction of 7.4%, with 13.6 the number needed to treat (p=0.03).

For patients in the ablation group, 92.6% of dysplasia and 88.2% of intestinal metaplasia was completely eradicated, compared with 27.9% of dysplasia and 0% of intestinal metaplasia for patients in the surveillance group.

Treatment-related adverse events occurred in 19.1% of patients in the ablation group; however, these were mild. The most common adverse event was esophageal stricture (11.8%), which all resolved with a median of one endoscopic dilation. "Ablation therapy is safe and is performed as an outpatient procedure," Dr. Bergman noted.

He thinks this approach is "ready for widespread use provided that the histological diagnosis of low-grade dysplasia is reliably made."

Ideal candidates are "young patients with a Barrett esophagus containing low-grade dysplasia in whom the diagnosis is confirmed by a pathologist with extensive experience in diagnosing Barrett neoplasia and preferably with this diagnosis being found at multiple endoscopic sessions," Dr. Bergman said.

Dr. Klaus Monkemuller, from the University of Alabama Birmingham, comments on the study in an editorial.

"The rigorous conduct of the trial, the centralized expert pathology review, the low rate of loss to follow-up, the high-caliber quality control, the expert center participation, the hands-on training of investigators, and the inclusion of more than the minimum planned enrollment (136 instead of 126 patients) make this an important study in the field," Dr. Monkemuller writes.

He says the study "provides a strong argument to shift the current approach for earlier intervention in patients with Barret esophagus and low-grade dysplasia. A proactive endoscopic approach to eliminate dysplasia may result in reduced morbidity and mortality related to the progression of this disease."

However, Dr. Monkemuller says "several important points should be emphasized before proceeding with ablation procedures for all patients with Barrett esophagus and low-grade dysplasia."

He points out that only patients with expert pathologist-confirmed low-grade dysplasia were included in the trial.

He thinks "better ways to stratify risk among patients with Barrett esophagus are needed to ensure that ablative therapies are offered to those likely to have disease progression."

Dr. Monkemuller also notes that ablative therapy did not fully eliminate risk of disease persistence or progression, with one-fourth of patients needing additional endoscopic interventions to complete the tissue elimination.

The fact that only expert centers participated in the trial "may render the results less reproducible in general practice; however, settings that have well-trained staff and equipment may also perform these endoscopic resection and ablation techniques," Dr. Monkemuller adds.

SOURCE: http://bit.ly/1pxgx8o and http://bit.ly/1jDZTCv

JAMA 2014;311:1205-1206,1209-1217.


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