Nonerosive GERD patients not prone to develop esophageal adenocarcinoma

Patients with nonerosive gastroesophageal reflux disease (GERD) show no higher incidence of esophageal adenocarcinoma (EAC) when compared with the general population, according to a study.

“This finding suggests that patients with confirmed nonerosive GERD are not susceptible to develop EAC and may not require repeated endoscopic examinations regarding assessment of cancer risk,” the researchers said.

All patients in hospital and specialized outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019 were included in this population-based study. A total of 486,556 adults who underwent endoscopy met the eligibility criteria. Of these, 285,811 were included in the nonerosive GERD cohort and 200,745 in the validation cohort with erosive GERD.

Nonerosive GERD referred to an absence of esophagitis and any other esophageal diagnosis at endoscopy, while erosive GERD, which was examined for comparison, referred to the presence of esophagitis at endoscopy.

The investigators assessed the incidence rate of EAC during 31 years of follow-up. They calculated the standardized incidence ratios (SIRs) by dividing the observed number of EAC in each cohort by the expected number, which was derived from the general populations in the three countries of the corresponding age, sex, and calendar period.

In the nonerosive GERD cohort, 228 patients developed EAC during 2,081,051 person-years of follow-up, corresponding to an incidence rate of 11.0 per 100,000 person years. Such incidence was comparable to that of the general population (SIR, 1.04, 95 percent confidence interval [CI], 0.91‒1.18) and did not increase during 15‒31 years of follow-up (SIR, 1.07, 95 percent CI, 0.65‒1.65). [BMJ 2023;382:e076017]

In the erosive GERD cohort, 542 patients developed EAC during 1,750,249 person-years of follow-up, which corresponded to an incidence rate of 31.0 per 100,000 person-years. This group showed a higher overall SIR at 2.36 (95 percent CI, 2.17‒2.57), which became more evident with longer follow-up.

“Patients with GERD symptoms, but with normal esophageal mucosa, seem to be largely unrelated to EAC, even after a long follow-up,” the researchers said.

“The finding may represent a shift in how to consider patients’ risk of tumour development based on endoscopic GERD phenotype, where patients with nonerosive GERD may be treated as the general population, whereas those with erosive GERD might benefit from being reassessed,” they added.

A previous study in a Danish population consisting of 7,655 patients examined the risk of EAC in those with nonerosive GERD and found only one patient who developed EAC during follow-up. Although the result was inconclusive, it suggested a low incidence of EAC in patients with nonerosive GERD. [Clin Gastroenterol Hepatol 2012;10:475-480]

Smaller natural history studies also reported that nonerosive GERD was less likely to progress to erosive GERD or Barrett’s esophagus. [Dig Liver Dis 2006;38:163-168; J Clin Gastroenterol 2006;40:398-404]

“[The current] 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 EAC, mainly dysphagia, as recommended for all individuals,” the researchers said.

“This message contrasts with today’s clinical practice, in which many patients with diagnosed nonerosive GERD undergo repeated upper endoscopies, which might be both costly and ineffective,” they added. [Dis Esophagus 2017;30:1-9]