Endoscopic Monitoring May Not Be Needed for Nonerosive GERD

Marilynn Larkin

September 27, 2023

Patients with confirmed nonerosive gastroesophageal reflux disease (GERD) are not at greater risk for esophageal cancer compared with the general population and are unlikely to need additional endoscopic monitoring for cancer, new research suggests.

By contrast, patients with erosive disease had more than double the incidence of esophageal cancer.

"We expected a less-strong association with cancer among patients with nonerosive GERD compared to those with erosive GERD, [and] the results do make sense in view of the fact that the nonerosive GERD patients had normal esophageal mucosa at endoscopy," Jesper Lagergren, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

The findings "suggest that in patients with GERD, a normal endoscopy indicates that the risk of cancer development in the esophagus is low," he said. "If future research confirms our results, no monitoring would be needed for patients with known nonerosive GERD."

However, a related editorial suggests there may be other reasons to endoscopically monitor patients with nonerosive GERD.

The study was published online September 13 in the BMJ, as was the editorial.

Erosive GERD Raises Risk

To assess the incidence rate of esophageal cancer among patients with nonerosive GERD compared with the general population, the investigators analyzed records from 486,556 patients in hospital and specialized outpatient centers in Denmark, Finland, and Sweden who underwent endoscopy from 1987 to 2019.

A total of 285,811 patients were included in the nonerosive GERD cohort, and 200,745 were included in a validation cohort of patients with erosive GERD.

Nonerosive GERD was defined by the absence of esophagitis and any other esophageal disorder at endoscopy. Erosive GERD was defined by esophagitis at endoscopy.

The incidence rate of esophageal cancer was assessed for up to 31 years of follow-up, with the median being 6.3 years.

In the nonerosive GERD cohort, 228 patients developed esophageal cancer during nearly 2.1 million person-years of follow-up. The incidence rate was 11 per 100,000 person-years, similar to that of the general population (standardized incidence ratio, 1.04) and did not increase with longer follow-up.

In the erosive GERD cohort, 542 patients developed esophageal cancer over almost 1.8 million person-years. This corresponded to an incidence rate of 31 per 100,000 person-years, or an increased overall standardized incidence ratio of 2.36, which became more pronounced with longer follow-up.

"This finding suggests that endoscopically confirmed non-erosive [GERD] does not require additional endoscopic monitoring for esophageal adenocarcinoma," the authors conclude.

'Dynamic' Progression

In a related editorial, Jerry Zhou, PhD, and Vincent Ho, MD, both of Western Sydney University, Penrith, New South Wales, Australia, write that the finding that patients with nonerosive disease do not have to undergo additional endoscopic evaluations for cancer is in line with previous research.

However, they add, "the more pressing rationale for re-evaluating these patients would be the potential for progression to conditions such as erosive reflux disease or Barrett's esophagus." Longitudinal studies have shown that GERD progression is dynamic, and so the development of erosive disease after nonerosive disease is feasible.

"Widespread use of proton-pump inhibitors complicates our understanding" of GERD progression, they note. Although study participants were advised not to take antireflux medications in the weeks prior to their endoscopy, "uncertainties about previous treatments remain due to the study's design." Some participants without erosive disease at baseline may have had it in the past.

Zhou and Ho also postulate that rather than being a progressive disease, nonerosive and erosive GERD might be two distinct conditions with different features and underpinnings.

Although valuable, the study "prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease. The changing progression of gastroesophageal reflux disease, the complex influence of proton pump inhibitors, and the potential for a range of underlying pathophysiological causes requires a more comprehensive diagnostic perspective," they conclude.

Lagergren said that his group plans to assess whether treatment of nonerosive GERD should be different from erosive GERD.

The study was funded by the Swedish Research Council, Swedish Cancer Society, and Nordic Cancer Union. No competing interests were declared.

BMJ. Published online September 13, 2023. Full text; Editorial

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