Non-Erosive GERD May Not Increase Risk of Esophageal Cancer

Patients with non-erosive gastroesophageal reflux disease (GERD) appear to have a similar incidence of esophageal adenocarcinoma as the general population, according to a large Nordic population-based cohort study with up to 31 years of follow-up.

In nearly 500,000 adults who underwent an endoscopy in Denmark, Finland, and Sweden, the incidence rate of esophageal adenocarcinoma was 11 per 100,000 person-years among those with non-erosive GERD, which was similar to that of the general population (standardized incidence ratio [SIR] 1.04, 95% CI 0.91-1.18), and did not increase with longer follow-up (SIR 1.07, 95% CI 0.65-1.65 for 15-31 years of follow-up), reported Jesper Lagergren, MD, PhD, of the Karolinska Institutet and Karolinska University Hospital in Stockholm, and colleagues.

In contrast, people with erosive GERD had an incidence rate of esophageal adenocarcinoma of 31 per 100,00 person-years, showing an overall SIR of 2.36 (95% CI 2.17-2.57), which became more pronounced with longer follow-up, they noted in The BMJ.

"Thus, this study suggests that physicians do not need to consider referring patients with GERD with a previous normal upper endoscopy for repeat endoscopy unless they develop warning symptoms of esophageal adenocarcinoma, mainly dysphagia, as recommended for all individuals," the authors wrote. "This message contrasts with today's clinical practice, in which many patients with diagnosed non-erosive GERD undergo repeated upper endoscopies, which might be both costly and ineffective."

GERD is the main risk factor for esophageal adenocarcinoma, and patients with GERD symptoms are often referred for upper endoscopy to look for mucosal abnormalities, including erosive esophagitis and metaplasia (Barrett's esophagus), the precursor conditions to esophageal adenocarcinoma, Lagergren and team said. While the link between esophagitis and esophageal adenocarcinoma is well established, no previous research has reliably examined the risk of developing esophageal adenocarcinoma in patients with endoscopically confirmed non-erosive GERD.

"Non-erosive reflux disease has distinguishing pathogenic features including low mucosal permeability, heightened visceral sensitivity, and psychological comorbidities," noted Jerry Zhou, PhD, and Vincent Ho, PhD, of Western Sydney University in New South Wales, Australia, in an accompanying editorial. "A nuanced diagnostic approach is needed encompassing symptom severity, oesophageal pH monitoring, and response to treatment with proton pump inhibitors."

This study "prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease," they added. "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."

For this study, Lagergren and colleagues used data from healthcare records in Denmark from 1995 to 2019, Finland from 1987 to 2018, and Sweden from 2006 to 2019. The 486,556 patients included in the study were diagnosed with GERD and had undergone at least one upper endoscopy; 285,811 had non-erosive GERD (median age 59, 58.7% women) and 200,745 had erosive GERD and were included in the validation cohort (median age 58, 55.4% men).

Follow-up started 12 months after the index endoscopy and ended either with esophageal cancer diagnosis, death, or the end of the study period, whichever came first.

Over 2,081,051 person-years of follow-up (median follow-time 6.3 years) in the non-erosive GERD cohort, 228 patients developed esophageal adenocarcinomas, 21.2% underwent a follow-up endoscopy, and 1.1% underwent anti-reflux surgery.

Women were found to have a slightly increased standardized incidence ratio of esophageal adenocarcinoma (1.38, 95% CI 1.08-1.73), but no major differences were noted for age.

Over 1,750,249 person-years of follow-up (median follow-up time 7.8 years) in the erosive GERD validation cohort, 542 patients developed esophageal adenocarcinomas, 26.9% underwent follow-up endoscopy, and 1.9% underwent anti-reflux surgery. Standardized incidence ratios were increased in all analyses stratified by age and sex.