A study recently published in the Journal of the American Medical Association (JAMA) supports the use of Covidien's (Dublin, Ireland) endoscopic ablation therapy in treating certain Barrett's esophagus patients.
The SUrveillance vs. RadioFrequency ablation trial (SURF) was a multi-center, randomized, investigator-sponsored clinical trial that compared the Covidien Barrx RF Ablation System with endoscopic surveillance in patients with Barrett's esophagus and a confirmed diagnosis of low-grade dysplasia. The study enrolled 136 patients at nine European sites between June 2007 and June 2011.
"In patients with Barrett's esophagus containing confirmed low-grade dysplasia, endoscopic ablation significantly reduced disease progression to high-grade dysplasia and esophageal cancer as compared to surveillance alone," said principal investigator Jacques Bergman, MD, PhD, professor of gastrointestinal endoscopy, and director of endoscopy at the Academic Medical Center (Amsterdam, The Netherlands). "The difference in the disease progression outcome between the two groups was so large, in fact, that the data safety monitoring board overseeing the trial recommended early stoppage of the trial and patients in the control group were then offered endoscopic ablation."
Barrett's esophagus develops as a result of chronic injury from gastroesophageal reflux disease (GERD). The normal esophageal lining is replaced with abnormal cells (known as Barrett's tissue), putting patients at greater risk of developing cancer of the esophagus.
Patients with Barrett's who ultimately develop cancer typically do so through a series of steps, starting with early Barrett's, then low-grade dysplasia or high-grade dysplasia and then cancer.
Bergman told Medical Device Daily that over the past 40 years the incidence of esophageal cancer has increased dramatically, mostly in Western countries. Because of its sharp rising incidence rate, esophageal cancer has generated a lot of interest, he said. He also noted that the cancer has a poor prognosis, and that the five-year survival rate of people diagnosed with this form of cancer is poor.
About seven years ago, RF ablation came into play as a potential treatment option for high-grade dysplasia and, Bergman says, it worked "very, very well."
"With the results being so good and RF ablation being relatively easy and safe, the question came up, should we start treating all Barrett's esophagus patients?" He said that doing RF ablation for all Barrett's patients would probably be "pretty aggressive" but the gray area is low-grade dysplasia because the diagnosis for low-grade dysplasia is hard to make and is something that is currently diagnosed by the pathologist based on random biopsies taken during endoscopy.
"If the pathologist calls it cancer or high-grade dysplasia we would go back and start treating, but if it is called low-grade dysplasia, we're never really sure what we should be doing with it," Bergman said. In the literature, he said, the progression rate of low-grade dysplasia varies significantly and pathologists struggle to make a correct diagnosis.
"Pathologists get confused, is it inflammation or is it dysplasia, especially those pathologists who do not see a lot of dysplasia and do not see a lot of high-grade dysplasia and cancers," Bergman said.
In fact, Bergman told MDD, the diagnosis of low-grade dysplasia is so subjective that if the same biopsies are reviewed by a group of expert pathologists the diagnosis "dramatically changes" compared to a less experienced pathologist. "Low-grade dysplasia is over-diagnosed, but it's also underestimated," he said, adding that the low-grade dysplasia "really has a very high progression rate."
Knowing that, and knowing that RF ablation systems such as Covidien's Barrx has been proven to be a safe and effective tool for high-grade dysplasia and cancer, investigators wanted to look at treating low-grade dysplasia the same way.
The SURF trial was supported, in part, by a grant from Covidien GI Solutions and the Maag Lever Darm Stichting grant from the Dutch Digestive Diseases Foundation.
Covidien's Barrx RF Ablation System is used as part of an endoscopic procedure and uses radiofrequency energy to coagulate tissue and remove the Barrett's epithelial tissue. In the U.S., the Barrx system is indicated for use in the coagulation of bleeding and non-bleeding sites in the gastrointestinal tract including but not limited to, the esophagus. Indications include esophageal ulcers, Mallory-Weiss tears, arteriovenous malformations, Angiomata, Barrett's esophagus, Dieulafoy lesions, and Angiodysplasia.
While the SURF trial did confirm the investigators' expectations that endoscopic RF ablation in patients confirmed to have low-grade dysplasia significantly reduced disease progression as compared to surveillance alone, Bergman says the real issue is pathology diagnosis of low-grade dysplasia. The development of better risk stratification tools would be one strategy to address this problem, he said.
If there was a test that could measure for a specific biomarker, such as a protein or a gene, that would be more objective than assessment by a pathologist alone, Bergman said. "If we have that, then why stick to low-grade dysplasia?" If a patient with Barrett's esophagus was shown to have a high risk of the disease progressing, they too might be considered a candidate for endoscopic RF ablation.