Abstract
OBJECTIVE: High-risk differentiated thyroid cancer (DTC) patients show variable outcomes. While postoperative stimulated thyroglobulin (STg) is a recognized predictive marker, the prognostic significance of unstimulated thyroglobulin (UTg) is still unexplored. This study aims to assess the prognostic value of postoperative UTg in high-risk DTC patients. DESIGN: Retrospective cohort study (2015-2024) at two Brazilian tertiary hospitals. PATIENTS: One thousand DTC patients were identified, of which 144 were high-risk. Fifty seven patients met the inclusion criteria. METHODS: Clinical, pathological, and laboratory data were collected. Outcomes were categorized as favorable (excellent/indeterminate responses) or unfavorable (biochemical/structural incomplete responses). Receiver Operating Characteristic (ROC) curves determined cutoff values for predicting outcomes and metastases. RESULTS: Significant predictors of unfavorable outcomes included advanced age (p = 0.048), larger tumor size (p = 0.002), higher UTg (p < 0.001), and STg (p < 0.001). UTg was an independent risk factor for 1-year outcomes (OR = 0.008; 95% CI: 0.001-0.088; p < 0.001). UTg cutoff of 2.1 ng/mL distinguished outcomes with high sensitivity (83.3%), specificity (96.0%), and accuracy (90.7%). A higher cutoff of 3.8 ng/mL identified metastases (sensitivity 86.4%, specificity 90.5%). UTg showed non-inferiority to stimulated thyroglobulin (STg) in predicting outcomes (p = 0.964) and metastasis (p = 0.980). CONCLUSION: Postoperative UTg is a strong prognostic marker in high-risk DTC patients, providing a non-inferior alternative to STg with greater accessibility and fewer side effects. We propose a clinical algorithm to optimize the management of these cases. When UTg levels exceed 2.1 ng/mL, particularly higher than 3.8 ng/mL, investigation of potentially resectable metastatic foci should be considered before radioiodine therapy. Prospective studies are needed to validate this algorithm.