The global, regional, and national burden of early, middle, and late-onset esophageal cancer and trends from 1990 to 2021: a systematic analysis of the Global Burden of Disease Study 2021.

Background: Although the overall burden has gradually decreased, our understanding of the differences in disease burden across various age groups remains incomplete and controversial. This study aimed to provide an updated estimate of the esophageal cancer burden, with a focus on temporal trends and age-specific patterns. Methods: We extracted data from the Global Burden of Disease Study (GBD) 2021. Esophageal cancer was grouped into three groups: early-onset (EOEC, 15-49 years), middle-onset (MOEC, 50-69 years), and late-onset esophageal cancer (LOEC, ≥70 years). Age-standardized rates (ASRs) ensured the comparability of age-standardized incidence rate (ASIR), mortality rate (ASMR), and disability-adjusted life-years (DALYs) rate (ASDR). Joinpoint regression identified temporal trends, and average annual percent change (AAPC) with 95% confidence intervals (CIs) was calculated. Furthermore, we conducted frontier, decomposition, cross-country inequality, and risk factor analyses. Bayesian age-period-cohort (BAPC) model was utilized to forecast future epidemiological trajectories from 2022 to 2035. Results: Globally, although the ASIR of EOEC declined from 1.95 per 100,000 in 1990 to 1.08 in 2021 with an AAPC of -1.9 (95% CI: -2.05 to -1.74, P<0.001), joinpoint regression analysis revealed that the ASIR of LOEC increased from 2014 to 2021. At regional levels, the highest ASRs of early, middle, and late-onset esophageal cancer were mainly observed in Sub-Saharan Africa and East Asia. Moreover, higher disease burden was found in lower sociodemographic index (SDI) countries. Smoking was the most important risk factor for esophageal cancer globally. Furthermore, the ASIR of EOEC and LOEC were projected to increase worldwide from 2022 to 2035. Conclusions: Our findings highlighted the need for targeted cancer control strategies that address population-specific needs, particularly with respect to age, gender, and sociodemographic disparities.