Oesophageal Adenocarcinoma after Surgery and Medication Against Gastro-Oesophageal Reflux Disease in a Nordic Cohort Study

Abstract

Background: Gastro-oesophageal reflux disease (GORD) increases risk of oesophageal adenocarcinoma (OAC), but whether antireflux therapy prevents OAC is uncertain. We aimed to clarify this issue and assess potential differences after surgical and medical treatment. Methods: Multinational, population-based cohort study including individuals with GORD from the five Nordic countries in 1964-2014. The exposure was antireflux surgery or medication and the outcome was OAC. First, OAC risk after antireflux surgery and medication in the cohort was compared with the respective corresponding background population by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (95%CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95%CIs, was used to compare antireflux surgery with medication in relation to OAC risk. Findings: Among 942,071 GORD patients, 48,863 underwent surgery and 893,208 received medication. Compared to the background population, OAC risk did not decrease following surgery (SIR=4.90 [95%CI 3.62-6.47] 1-<5 years and SIR=4.57 [95%CI 3.44-5.95] ≥15 years after surgery) or medication (SIR=2.37 [95%CI 2.17-2.59] 1-<5 years and SIR=3.07 [95%CI 2.65-3.54] ≥15 years after medication). Similarly, no decrease was found for patients with severe GORD over time after surgical (SIR=6.09 [95%CI 4.39-8.23] 1-<5 years and SIR=5.27 [95%CI 3.73-7.23] ≥15 years) or medical (SIR=3.61 [95%CI 3.19-4.07] 1-<5 years and SIR=3.82 [95%CI (3.19-4.55] ≥15 years) antireflux therapy. The HRs of OAC were stable over time over time after surgery compared with medication (HR=1.71 [95%CI 1.26-2.33] 1-<5 years and HR=1.69 [95%CI 1.24-2.30] ≥15 years after treatment), and remained stable over time after treatment in participants with severe GORD (HR=1.56 [95%CI 1.11-2.20] 1-<5 years and HR=1.57 [95%CI 1.08-2.26] ≥15 years after treatment). Interpretation: Medical and surgical treatment of GORD does not seem to reduce OAC risk. Funding: Nordic Cancer Union, Swedish Cancer Society and Swedish Research Council. Declaration of Interest: None. Ethical Approval: All required ethical and data permissions were retrieved from the relevant authorities within each country (The Danish Data Protection Agency; Population Register Centre, National Institute for Health and Welfare, Statistics Finland; The Icelandic Data Protection Authority, The National Bioethics Committee; Regional Ethics Committee, Norway; and Regional Ethics Committee, Sweden).