Evolving epidemiology and prognostic impact of young age in endometrial cancer: a multicenter retrospective study

This multicenter retrospective study characterized epidemiological trends and high-risk factors in endometrial cancer (EC) in China from 2000 to 2019, and evaluated whether young age (≤45 years) is an independent prognostic factor, with tumor aggressiveness as a potential mediator.

We reviewed records of 16,798 EC patients from 29 centers; 11,019 with complete clinical data were included for survival analysis. Propensity score matching (PSM) balanced clinicopathological features between patients aged ≤45 and >45 years. Kaplan-Meier and multivariable Cox models assessed survival. Mediation analysis used a latent variable for tumor aggressiveness, incorporating grade, lymphovascular space invasion (LVSI), and myometrial invasion depth.

EC incidence markedly increased, with a modest decline in mean age at diagnosis. Patients aged ≤45 years exhibited less aggressive tumors: higher proportions of G1/G2 histology, absence of LVSI, and superficial myometrial invasion (all p<0.001). After PSM, which yielded 1,432 matched pairs, young age remained independently associated with improved overall survival (hazard ratio [HR]=0.54; 95% confidence interval [CI]=0.39-0.75; p=0.001) and disease-free survival (HR=0.64; 95% CI=0.46-0.89; p=0.008). Tumor aggressiveness significantly mediated the age-survival association (indirect effect coefficient, -0.101; p<0.001), accounting for a substantial portion of the survival advantage.

EC incidence is rising and age at diagnosis is declining in China. Young age is an independent prognostic factor for improved survival, with part of the benefit attributable to less aggressive tumor phenotypes. These findings support integrating age into risk stratification and developing age-stratified management strategies.