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Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease.

BACKGROUND AND AIMS
Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with a decreased incidence and mortality in upper gastrointestinal cancer (esophageal, gastric, or duodenal cancer).


METHODS
Population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HR) with 95% confidence intervals (CI).


RESULTS
Among 1,062,740 patients with GERD (median age 58 years; 52% women) followed for mean 7.0 person-years, 5,324 (0.5%) developed upper gastrointestinal cancer and 4,465 (0.4%) died from such cancer. Patients who had undergone a negative upper endoscopy had 55% decreased risk of upper gastrointestinal cancer compared to those who did not undergo endoscopy (HR=0.45, 95% CI 0.43-0.48), a decrease which was more pronounced during more recent years (HR 0.34, 95% CI 0.30-0.38 from 2008 onwards), and was otherwise stable over sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR=0.39, 95% CI 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for five and at least ten years, respectively.


CONCLUSION
Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.