Age as a Risk Stratification Factor in Surgically Treated Low-Risk Indeterminate Thyroid Nodules: insight from the TIRETA Study

Abstract Objectives To evaluate whether age acts as a clinically meaningful risk stratification factor in surgically treated TIR3A/Bethesda III nodules. Methods We retrospectively reviewed consecutive adult patients with TIR3A cytology who underwent thyroid surgery between 2015 and 2025 at a single tertiary centre. Only cases with definitive histology were included. The primary outcome was malignancy at final histology. Age was analysed as both a continuous and categorical variable using univariable and multivariable logistic regression models. Non-linear associations were explored with restricted cubic splines. Discriminative performance was assessed by receiver operating characteristic (ROC) curve analysis and decision curve analysis. Results Among 435 surgically treated patients (mean age 54 ± 14 years; 23.7% male), 76 (17.5%) had differentiated thyroid cancer. Increasing age was independently associated with a lower risk of malignancy (adjusted OR per year 0.98; 95% CI 0.96–0.99; p=0.015). Age demonstrated modest discriminative performance (AUC 0.608; 95% CI 0.536–0.681). Model-based estimates indicated that age alone was associated with an absolute shift in malignancy probability of approximately 8–10 percentage points between 40 and 60 years. Conclusions In TIR3a/Bethesda III nodules, age functions as a clinically meaningful risk modifier rather than a stand-alone diagnostic tool. Although insufficient to guide surgery independently, age may help contextualize malignancy probability and support shared decision-making, particularly when molecular testing is unavailable or inconclusive.