Comparative Performance of the 2015 and 2025 American Thyroid Association Initial Recurrence Risk Stratification Systems in Differentiated Thyroid Cancer

Background: The 2025 American Thyroid Association (ATA) guidelines have introduced refined clinicopathologic criteria for risk stratification in differentiated thyroid cancer (DTC). However, the real-world prognostic performance and reclassification consequences of this update compared with the 2015 system remain unevaluated. Methods: We conducted a retrospective cohort study at a tertiary referral center in China. Adult patients who underwent initial thyroidectomy for pathologically confirmed DTC between January 2008 and December 2018 were included, with follow-up extending through October 30, 2025. We compared the 2015 and 2025 ATA initial risk stratification systems. The primary outcome was structural recurrence-free survival. Performance was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and decision curve analysis (DCA). Findings: Among 1508 patients (median age 43 years [IQR 33–53]; 1147 [76.1%] female), 120 (8.0%) developed structural recurrence during a median follow-up of 8.9 years. The 2025 ATA system demonstrated superior discrimination compared with the 2015 system (5-year AUC 0.78 [95% CI 0.74–0.82] vs 0.73 [0.69–0.78]; p=0.004), although both systems showed significant risk stratification (log-rank p<0.001). Reclassification analysis revealed that the 2025 system reassigned 41.7% of patients with recurrence to higher-risk categories but also reassigned 38.8% of recurrence-free patients to higher-risk categories. This yielded an additive NRI of 9.7% (0.097) and an absolute NRI of −22.6%. Multivariable analyses identified the revised multifocality criteria and the presence of two or more low-to-intermediate risk features as the major contributors to this misclassification (risk inflation). Conversely, refined compartment-based lymph node stratification was associated with improved classification accuracy. Decision curve analysis demonstrated greater net clinical benefit for the 2025 system across clinically relevant threshold probabilities. Interpretation: The 2025 ATA risk stratification system improves the identification of high-risk patients compared with the 2015 system. However, the revised criteria may lead to risk inflation for recurrence-free patients. Clinicians should balance the enhanced sensitivity against the potential risk of overtreatment when applying the 2025 guidelines.​