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 introduced significant modifications to the initial risk stratification system for differentiated thyroid cancer (DTC). However, the real-world prognostic performance and stage migration effects of these updates 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 disease-free survival (SDFS). Performance was assessed using area under the receiver operating characteristic curve (AUC), reclassification analysis, and decision curve analysis (DCA).

Results

Among 1508 patients (median age 43 years, interquartile range [IQR] = 33-53; 1147 [76.1%] female), 120 (8.0%) developed events during a median follow-up of 8.9 years (IQR = 7.56-10.80). The 2025 ATA system demonstrated superior discrimination compared with the 2015 system (ΔAUC 0.0455 [confidence interval or CI: 0.0147-0.0764], 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. 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 reclassification (risk inflation). Conversely, refined compartment-based lymph node stratification was associated with improved classification accuracy. DCA demonstrated greater net clinical benefit for the 2025 system across clinically relevant threshold probabilities.

Conclusions

The 2025 ATA initial risk stratification system significantly improves prognostic discrimination compared with the 2015 system. However, the enhanced sensitivity comes with a specificity trade-off, leading to substantial upward risk reclassification for recurrence-free patients. These real-world findings provide critical insights for clinicians to balance intensified surveillance against the potential for overtreatment under the new guidelines.