Sex disparities in papillary thyroid cancer survival: Divergent patterns of relative and absolute effects across the age spectrum

Abstract

Purpose This retrospective cohort study aimed to reevaluate the prognostic impact of sex and determine whether age modifies the effect of sex on cancer-specific survival (CSS) in PTC patients. Methods Data for PTC patients diagnosed between 2004 and 2015 were retrieved from the SEER database. The primary outcome was CSS. The effect of Sex was evaluated using both relative (hazard ratios, HRs) and absolute measures (survival differences). Additionally, the effect of sex modified by age was assessed using restricted cubic spline curves from the Cox and Poisson models, with further analysis of the interaction between sex and age. Results Of 77,349 patients, 16,152 (20.9%) were male. Men exhibited older age, more aggressive clinicopathological features, and received more radioactive iodine treatment. Multivariate Cox analysis determined male sex as an independent risk factor (adjusted HR: 1.46 (1.24–1.70). The 10-year and 15-year survival differences between men and women were 0.46% (95% CI, 0.25%−0.67%) and 0.77% (95% CI, 0.31%−1.22%), respectively. Moreover, a nonlinear effect for sex across age was observed, with HRs for men plateauing below age 50 and decreasing thereafter. Importantly and conversely, before age 50, the absolute survival difference increased slightly with age, but after 50, it significantly widened. Furthermore, A significant negative multiplicative interaction between sex and age was found. Conclusions Our analyses provide robust evidence that male sex is indeed an independent risk factor for CSS in PTC patients. Although younger female patients show a relative survival advantage, this does not translate into a substantial absolute benefit, which widens with advancing age.