Age Modifies the Prognostic Impact of Sex in Follicular Thyroid Carcinoma: A SEER Database Analysis.
retrospective_cohort · Level III
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- Also identified by DOI 10.1245/s10434-026-19343-4.
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Abstract
The prognostic significance of sex in follicular thyroid carcinoma (FTC) remains controversial. This study aimed to clarify the prognostic significance of sex and examine whether age modified this effect in FTC. Data for 9104 patients with FTC diagnosed between 2004 and 2021 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was disease-specific survival (DSS). The effect of sex was evaluated using both relative (hazard ratios [HRs]) and absolute measures (absolute survival differences). Additionally, the effect of sex modified by age was assessed using restricted cubic spline (RCS) curves derived from Cox models. The interaction between sex and age was further analyzed on multiplicative and additive scales. Among 9104 patients (72.5% female), male patients presented with more aggressive characteristics. While unadjusted analyses showed worse DSS in male individuals (HR: 1.53, 95% confidence interval [CI]: 1.17-2.00), multivariable adjustment eliminated this difference (HR: 1.06, 95% CI: 0.79-1.42). However, RCS analysis revealed significant age-dependent heterogeneity (P for nonlinearity < 0.001). Male patients under 55 years experienced markedly worse survival (adjusted HR: 2.23, 95% CI: 1.41-3.53) with a 1.0% absolute 10-year survival difference, while this disadvantage diminished and potentially reversed after 55 years (HR: 0.72, 95% CI: 0.50-1.05). Further interaction analysis confirmed significant antagonistic effects on both multiplicative (interaction ratio, 0.32; P < 0.001) and additive scales (relative excess risk due to interaction [RERI], -2.57; 95% CI: -4.52 to -0.63). Our findings reveal that age critically modifies sex-based prognosis in FTC. Young male individuals face a 2.23-fold higher mortality that diminishes and potentially reverses with advancing age. This significant interaction necessitates age-stratified, sex-specific risk assessment for personalized FTC management.