Assessing progression, impact of radiofrequency ablation in Barrett’s esophagus

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From the AGA Journals

Assessing progression, impact of radiofrequency ablation in Barrett’s esophagus

Publish date: September 1, 2015

By

Amy Karon

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Low progression rate in Barrett’s can be controlled with RFA

These two studies highlight two different hot topics in the management of patients with a Barrett’s esophagus. The first is the low rate of neoplastic progression in patients undergoing surveillance for nondysplastic BE. The second relates to the management of patients with low-grade dysplasia (LG

Dr. Jacques Bergman

Population-based BE surveillance studies have shown lower progression rates than have prospective surveillance studies. The biggest difference between these two is that not all patients in population-based studies actually undergo subsequent surveillance endoscopies and/or surveillance is carried out less rigorously than in prospective surveillance studies. Patients who have undergone a baseline endoscopy showing no neoplasia first need to develop early neoplasia (which is generally asymptomatic) that then needs to progress to a symptomatic stage before they are diagnosed. During this interval they may die from other causes or may be lost to follow-up. Patients in strict surveillance programs will be diagnosed at an earlier stage and at a higher rate. This is especially true in the first years of follow-up, when the initial screening endoscopy has its largest effect. Over time, the difference then fades away as suggested by the 9% progression rate of both types of studies at 20 years of follow-up. Both perspectives are relevant for patients. For elderly patients with significant comorbidity, the 5-year data from population-based studies reassure them not to undergo surveillance endoscopies because even when an early cancer develops it is unlikely to bear any clinical relevance, whereas for patients with a long life expectancy, the 9% cancer risk at 20 years and the dismal prognosis of a symptomatic Barrett’s cancer may be strong arguments for participating in a surveillance program.

For patients with LGD, the situation is different: The rate of progression is much higher than that reported for nondysplastic BE, and with radiofrequency ablation (RFA), an effective and safe tool is at hand to significantly reduce this rate of neoplastic progression. Small et al. reported that only three patients need to be treated with RFA to prevent one patient from progressing to high-grade dysplasia or cancer. These data are in agreement with data from a prospective randomized study on the use of RFA for patients with a confirmed diagnosis of LGD. Most societies therefore consider a confirmed histologic diagnosis of LGD a justified indication for prophylactic ablation with RFA.

However, this does not imply that all patients with LGD should be ablated. First, only patients in whom the histologic diagnosis of LGD is confirmed by an expert BE pathologist should be considered for RFA. In approximately 75% of patients, the LGD diagnosis will be downstaged to nondysplastic BE upon expert review. Second, the lessons learned from the Kroep study also apply here: For an elderly LGD patient with or without significant comorbidity, the decision to proceed to RFA is different from the decision for patients with a longer life expectancy, especially if an intermediate solution – to continue endoscopic surveillance and proceed to endoscopic management in case neoplasia is diagnosed – is also considered.

Jacques Bergman, M.D., Ph.D., is professor of gastrointestinal endoscopy, director of endoscopy, at the Academic Medical Center, Amsterdam. He received research support for clinical studies and consulted for Covidien/Medtronic GI solutions.

FROM GASTROENTEROLOGY

References

Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.

The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.

Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).

For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.

In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.

Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).

The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.

Assessing progression, impact of radiofrequency ablation in Barrett’s esophagus

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