The prevalence of esophageal adenocarcinoma is increasing in the United States,1 presenting a major concern for gastroenterologists and fellows tasked with evaluating and managing patients who may have this malignancy. Higher cancer rates have driven researchers to further study Barrett’s esophagus (BE), a known precursor to esophageal adenocarcinoma,2 and the efficacy of BE interventions including radiofrequency ablation (RFA).

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Barrett’s esophagus pictured before treatment (left), during the ablative procedure using radiofrequency ablation (middle), and following treatment (right).

The estimated risk for adenocarcinoma in patients with BE is 0.5% per year, according to the American Gastroenterological Association (AGA)3; patients with BE but no dysplasia should undergo endoscopic surveillance for esophageal cancer every 3 to 5 years with intervals shortening depending on dysplasia severity.3 Those with BE and low-grade dysplasia (LGD) have already demonstrated an increased propensity for progression; advancing to high-grade dysplasia (HGD) or adenocarcinoma is estimated at up to 13.4% per year.3 There are a number of challenges associated with surveillance of BE, including but not limited to, sampling error and pathologic discordance.

“Surveillance really does not work,” said F. Scott Corbett, MD, gastroenterologist at Gastroenterology Associates of Sarasota in Sarasota, Florida. Dr. Corbett cited problems such as insufficient tissue sampling and variability of opinion among pathologists regarding dysplasia. Once cancer develops, prognosis is poor: Five-year survival is less than 15%,4 leading Dr. Corbett to encourage prevention over detection. As a treatment option, RFA, is considered appropriate for HGD; in one study, more than 73% of patients with HGD achieved complete eradication of intestinal metaplasia and reduced progression to esophageal cancer following RFA use (19% for non-RFA control group vs 2.4% for RFA patients, P=0.04).5 Similar acceptance is growing for patients with LGD.3 Exceptions include cases in which tissue specimens are sought for pathologic evaluation or for raised, nodular lesions, according to Virender K. Sharma, MD, director of the Arizona Center for Digestive Health in Gilbert, Arizona. “I recommend RFA for most LGD patients unless there are specific procedural risks or they do not want ablation,” he said. “I do not offer PDT [photodynamic therapy] or cryotherapy for LGD, but I do use EMR [endoscopic mucosal resection] in those with nodular LGD to obtain a better tissue specimen.”

Dr. Corbett noted that the utility of RFA in BE has been well established with more than 100 published peer-reviewed papers supporting efficacy, safety, durability, and cost-effectiveness. A recent review of RFA in BE reconfirmed low rates (≤5%, 95% confidence interval) of serious adverse events (AEs)6; stricture was the most common AE6 although stricture related to RFA, “is usually relatively easy to treat because the ablation is superficial,” Dr. Corbett added.

In a recent randomized controlled trial enrolling 136 BE patients with a diagnosis of LGD that had been confirmed by an expert panel, RFA significantly reduced malignant transformation.7 In this trial, called SURF (SUrveillance vs. RadioFrequency ablation), progression to HGD or adenocarcinoma at variable follow-up times (median follow-up 3 years) was 26.5% in a control group managed with surveillance and 1.5% (P<0.001) in patients randomized to RFA.7 The absolute risk reduction of 25% translated into a number needed to treat of 4 patients for halting progression and 13.6 for preventing adenocarcinoma over the follow-up period.7

“The trial clearly associates RFA with a significant reduction in the risk for malignancy in patients with LGD,” said Charles J. Lightdale, MD, professor of medicine at Columbia University Medical Center in New York City. “It provides data useful for counseling patients about options for managing risk.”

Srinadh Komanduri, MD, director of interventional endoscopy in the Division of Gastroenterology and Hepatology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, agreed. “On the basis of these data, I offer endoscopic eradication to essentially all BE patients with confirmed LGD,” he said, adding that exceptions would include patients whose expected life span would be too short to gain an advantage from eradication.

Although the prevalence of patients with nondysplastic BE who develop esophageal adenocarcinoma is low —less than 0.5% per year8—the interviewed experts agreed that RFA use in this patient population may be worthwhile, particularly in light of family history of cancer, among other factors. Despite the lack of randomized trial data to quantify the relative protection of RFA over surveillance in this population, benefit is a logical expectation for patients with nondysplastic BE but with multiple risk factors for progression. “I discuss RFA for young patients, in patients with long-segment BE, and in those with family history of adenocarcinoma,” Dr. Sharma said. “Also, I will discuss the pros and cons of RFA as a strategy to reduce cancer risk in patients with nondysplastic BE who request ablation. I believe patients with any stage BE should be informed of all treatment options so they can make an informed medical decision for themselves.”

V. Raman Muthusamy, MD, director of interventional endoscopy in the Division of Digestive Diseases at the University of California in Los Angeles, also offers RFA selectively to BE patients with nondysplastic disease using similar criteria: He considers RFA or other forms of eradication of intestinal metaplasia in patients younger than age 60, those with a BE segment longer than 3 cm, and in those with a family history of esophageal cancer. In patients with dysplastic BE who achieve complete eradication of intestinal metaplasia, follow-up intervals can be lengthened. “In patients with HGD, we perform a follow-up endoscopy every 3 months during the first year and then at yearly intervals. In LGD, we endoscope at 6 months, 1 year, 2 years, and then every other year if we do not see recurrence or new lesions,” he said. “After successful RFA in nondysplastic BE, we do the first endoscopic evaluation at 1 year but if BE has not recurred, we do not take another look for another 4 years.”

Dr. Corbett reported that low rates of recurrence may be important for encouraging use of RFA in patients with nondysplastic BE. “My hope is that future studies will show that patients who have had RFA for nondysplastic disease and have had no recurrence 6 years post-treatment may be able to stop surveillance,” Dr. Corbett said. This “would enhance the cost-effectiveness” of RFA in this population, although Dr. Corbett added that he is less optimistic that surveillance can ever be discontinued in those treated once LGD has developed.

The value of RFA in BE has encouraged its use in producing hemostasis in gastric antral vascular ectasia (GAVE) and controlling proctopathy secondary to radiation, among other clinical areas. In an open-label study for which Dr. Komanduri served as senior author, 86% of patients with GAVE remained transfusion independent 6 months after RFA.9 Moreover, although the basic premise of RFA has not changed since these devices were first approved, new designs of catheters and electrodes are increasing their versatility, according to Dr. Lightdale. “There have been some incremental advances that make the latest devices easier to use and more efficient in achieving complete eradication of the targeted tissue,” he said.

References

  1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97(2):142-146.
  2. Wang KK, Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103(3):788-797.
  3. Spechler SJ, Sharma P, et al; American Gastroenterological Association. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology. 2011;140(3):1084-1091.
  4. Eloubeidi MA, Mason AC, Desmond RA, et al. Temporal trends (1973-1997) in survival of patients with esophageal adenocarcinoma in the United States: a glimmer of hope? Am J Gastroenterol. 2003;98(7):1627-1633.
  5. Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med. 2009;360(22): 2277-2288.
  6. Orman ES, Li N, Shaheen NJ. Efficacy and durability of radiofrequency ablation for Barrett’s Esophagus: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11(10):1245-1255.
  7. Phoa KN, van Vilsteren FG, Weusten BL, et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014;311(12): 1209-1217.
  8. Wani S, Falk G, Hall M, et al. Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol. 2011;9(3):220-227.
  9. McGorisk T, Krishnan K, Keefer L, et al. Radiofrequency ablation for refractory gastric antral vascular ectasia (with video). Gastrointest Endosc. 2013;78(4):584-588.

Barrx 360 RFA Balloon Catheter Animation

Click here to see a video of radiofrequency ablation performed using a 360-degree balloon catheter.