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

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.