Age of onset by temporal and spatial changes and prognostic value for esophageal cancer

Abstract Background: Age plays a crucial role in the incidence and prognosis of esophageal cancer. In China, the age distribution of patients with esophageal cancer remains unclear, and comprehensive large-scale studies on its prognostic impact are lacking. Methods: Using a cohort of 294,523 patients with esophageal cancer, we compared onset age distributions across clinicopathological characteristics ( χ 2 test). Trends in the proportion of patients diagnosed under 60 years were analyzed using linear regression. Survival differences by age were assessed via Kaplan–Meier analysis and Cox regression (univariate and multivariate). Directed acyclic graphs defined causal relationships. Robustness was evaluated using multiple imputation and sensitivity analyses. Subgroup and propensity score matching analyses addressed confounding. Restricted cubic spline models explored nonlinear relationships between age and surgery rates, overall mortality risk, and perioperative mortality. Results: The proportion diagnosed under age 60 significantly declined over time ( P <0.05, R 2 = 0.96), with this younger demographic being more prevalent among males, high-incidence area, smokers, alcohol consumers, and those with family history (all P <0.001). Surgical rates decreased sharply beyond age 62. Advanced age was an independent predictor of poorer survival, with surgery offering the best prognosis compared with radiochemotherapy and symptomatic untreated, supported by subgroup and post-propensity score matching survival analyses. Mortality risk increased most rapidly with age in untreated patients (inflection at 65 years), followed by radiochemotherapy (63 years) and surgery (60 years), while perioperative mortality rose steeply beyond age 60. Conclusions: Male, residence in high-incidence area, smoking, alcohol intake, and positive family history were associated with earlier onset age of esophageal cancer; the proportion of patients under 60 years old declined significantly over time. While advanced age independently predicted poorer survival, it should not absolutely contraindicate surgery. A precise perioperative risk assessment system is crucial to balance surgical benefits and risks in the elderly.