Age-Dependent Effects of Gastric Cancer Screening Endoscopy on Mortality: A Nationwide Cohort Study

Background and Aim: Endoscopic screening for gastric cancer (GC) reduces mortality, but the optimal upper age limit and modifying role of comorbidity remain unclear. Methods: In a nationwide retrospective cohort study using the Korean National Health Insurance Service database linked to national mortality records, we identified individuals aged ≥40 years who underwent screening esophagogastroduodenoscopy between 2005 and 2010 and propensity score-matched non-screened controls. The primary outcome was GC-specific mortality. Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Hazard ratios (HRs) were estimated in the matched cohort. Results: Among 555,904 propensity score-matched individuals (277,952 per group), GC-specific mortality HRs showed an age-dependent gradient: below 1.0 at 50–59 (HR, 0.56; 95% CI, 0.34–0.92), 60–64 (0.65; 0.40–1.07), and 65–69 (0.82; 0.58–1.17); near 1.0 at 70–74 (0.99; 0.75–1.30) and 75–79 (0.92; 0.68–1.24); and elevated at ≥80 years (2.21; 1.49–3.27). Comorbidity further modified this association: HRs were below 1.0 in individuals with CCI <3 (0.86; 0.74–1.01) but elevated in those with CCI ≥3 (1.88; 1.42–2.49). In age–CCI analyses, point estimates favored screening across age groups up to age 75–79 years among individuals with CCI 0, but HRs exceeded 1.0 in most age groups with CCI ≥3. Post-endoscopy respiratory or cerebro-cardiovascular events increased with age and comorbidity. Conclusion: The mortality benefit of gastric cancer screening endoscopy diminished with advancing age and comorbidity burden, becoming of questionable value beyond age 70. At age ≥80 or in individuals with substantial comorbidity (CCI ≥3, present in 26.5% of screened participants aged ≥70 years), potential harms may outweigh benefits.