ArticleBalkan medical journal2026
Integrating the Interaction Between Extrathyroidal Extension and Tumor Size to Optimize T Stage in Differentiated Thyroid Cancer.
Article in Balkan medical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The American Joint Committee on Cancer (AJCC) T stage for differentiated thyroid cancer (DTC) has limited prognostic stratification capability, and the interaction between extrathyroidal extension (ETE) and tumor size remains inadequately characterized. Aims: To investigate the interaction between ETE and tumor size and to develop a modified T stage with improved prognostic stratification for DTC. Study Design: Retrospective, population-based cohort study. Methods: We analyzed 163,616 patients with DTC from the Surveillance, Epidemiology, and End Results database, divided into development (n = 106,516; 2004-2015) and validation (n = 57,100; 2016-2021) cohorts. Disease-specific survival was the primary outcome. We evaluated the interaction between ETE and tumor size on additive and multiplicative scales and developed a modified T stage using recursive partitioning analysis. Performance assessment included discrimination (C-index), calibration (Brier score), and five standard cancer staging criteria. Results: Significant positive additive interactions were observed between ETE and tumor size, with relative excess risk due to interaction (RERI) increasing from minimal ETE (MinETE) [RERI = 1.90; 95% confidence interval (CI): 1.02-2.78] to Gross4b ETE (RERI = 6.55; 95% CI: 2.74-10.35). In tumors > 2 cm, MinETE was associated with a 4.58-fold increased risk (95% CI: 3.77-5.55), compared with a 2.34-fold increase (95% CI: 2.05-2.66) in smaller tumors, indicating size-dependent prognostic effects. The modified T stage incorporating these interactions demonstrated improved discrimination (C-index: 0.775; 95% CI: 0.770-0.779) compared with the AJCC 8 Conclusion: The modified T stage incorporating size-dependent effects of ETE was associated with improved prognostic stratification compared with the AJCC 8
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