Oct. 22, 2019
Individuals with Barrett's esophagus (BE) are at increased risk of progression to esophageal adenocarcinoma. This risk increases for individuals who are also diagnosed with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). In these patients, the standard of care is treatment with radiofrequency ablation (RFA) after endoscopic resection of visible lesions.
Treatment with RFA and resection can reduce the risk of cancer progression and induce complete remission of intestinal metaplasia (CRIM), both endoscopically and histologically. However, recurrence of intestinal metaplasia (IM) and dysplasia after successful ablation is well documented. The estimated annual incidence rate is 9.5% for any recurrence and 2% for dysplastic recurrences.
Current clinical guidelines thus recommend periodic endoscopic surveillance — every three months during the first year after CRIM, and every six months during the second year and yearly thereafter. Some recent study data suggest that recurrence rates in patients who have achieved CRIM may decline after the first year. These data have led some to consider whether wider surveillance intervals after the first year might be warranted.
To explore this issue, a group of researchers conducted a multicenter, international cohort study assessing the timeline, location and patterns of recurrence in patients achieving CRIM after RFA. The results of the study were published in Gut in 2019.
Study design
The researchers obtained data on patients undergoing RFA for BE from prospectively maintained databases provided by five tertiary referral centers. Study participants included patients age 18 and older with endoscopically and histologically confirmed BE, with or without dysplasia, who underwent RFA between 2003 and 2016. Using these criteria, researchers identified 594 study participants who achieved CRIM between March 2004 and May 2017.
Study subjects underwent RFA after endoscopic assessment until CRIM was confirmed. The researchers defined CRIM as the absence of IM on biopsies from both the gastroesophageal junction (GOJ) and tubular esophagus, confirmed via two consecutive endoscopies performed at least three months apart. In addition to RFA, study subjects could receive argon plasma coagulation or multipolar coagulation as rescue (adjuvant) techniques for minimal residual BE islands.
Once CRIM was achieved, study subjects underwent surveillance using high-definition white light endoscopy and narrow band imaging with random biopsy specimens at three, six, nine and 12 months, and every year thereafter.
Researchers documented the location, visibility and dysplasia status of all recurrences, which were defined as the histological presence of IM with or without dysplasia on biopsy specimens taken from either the tubular esophagus or the GOJ or both after CRIM was achieved.
Results
- Of the study participants, 151 developed recurrent BE over a median interquartile range (IQR) follow-up of 2.8 (1.4 to 4.4) years.
- The cumulative recurrence risk of any BE within two years was 19%, with an additional 49% risk over the next 8.6 years.
- Recurrence incidence and timeline: Researchers found no evidence of a decrease in recurrence risk over time, with no clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia or cancer over the duration of follow-up. When follow-up time was doubled, researchers noted an estimated 2% change in the rate of recurrence for BE (95% confidence interval, -7% to 12%).
- Recurrence location: The majority (74.2%) of BE recurrences developed at the GOJ, 24.1% of which were dysplastic, and 25.8% of recurrences developed in the tubular esophagus. A significant proportion of dysplastic recurrences in the GOJ were not visible endoscopically. In contrast, the majority of recurrences in the tubular esophagus were visible endoscopically, and the yield of random biopsy sampling in the absence of visible lesions was very low — 1% for BE and 0.2% for dysplasia.
Conclusions and implications for clinical practice
According to Prasad G. Iyer, M.D., a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, and senior author on the Gut article, this study demonstrated that BE recurrence risk after CRIM remained constant over time in patients who achieved CRIM after RFA, when strict criteria for the definition of CRIM are applied. "Overall, our findings suggest that yearly endoscopic surveillance remains important in these patients, especially in patients with high-grade dysplasia and cancer at baseline," explains Dr. Iyer. "Lengthening of follow-up intervals, at least in the first five years after CRIM, may not be advisable."
Co-author David E. Fleischer, M.D., a gastroenterologist at Mayo Clinic's campus in Scottsdale, Arizona, adds that the study's data about recurrence location may also have implications for clinical practice. "We learned that that careful imaging and sampling of the gastroesophageal junction, even when visible lesions are absent, are critical to detecting recurrence," says Dr. Fleischer.
Co-author Herbert C. Wolfsen, M.D., a gastroenterologist Mayo Clinic's campus in Jacksonville, Florida, says that the results obtained from random biopsy sampling in the tubular esophagus were also noteworthy. "The low yield obtained from biopsies in the tubular esophagus suggest that we may need to reevaluate the guideline recommending random biopsies in the entire neosquamous epithelium in the absence of visible lesions," explains Dr. Wolfsen.
For more information
Sami SS, et al. Timeline and location of recurrence following successful ablation in Barrett's oesophagus: An international multicentre study. Gut. 2019;68:1379.