Differentiated Thyroid Cancer Long-Term Outcomes and Risk Stratification in Pediatric and Adolescent Patients: A 44-Year Retrospective Study

Background: Differentiated thyroid cancer (DTC) in children and adolescents is a rare but significant malignancy, often presenting at more advanced stages compared to adults, although it is associated with favorable long-term outcomes. This study aimed to identify prognostic factors and perform risk stratification with the goal of identifying low-risk patients who would benefit from a less radical treatment approach. Methods: This retrospective cohort study included patients aged 21 years and younger with DTC treated at the Institute for Oncology and Radiology of Serbia between 1980 and 2024. Results: The study analyzed 99 patients (39 children, 60 adolescents) with a median follow-up of 15.6 years (range: 0.6–43.6 years). No significant differences in long-term outcomes were observed between children and adolescents. Multivariate regression analysis identified a total number of more than 10.5 positive lymph nodes and extrathyroidal tumor extension as independent predictors of adverse events and event-free interval (EFI). Using these prognostic factors, patients were stratified into three groups: low-risk (no risk factors), intermediate-risk (one of two risk factors), and high-risk (both risk factors). Statistically significant differences in EFI were observed among the three groups. Notably, none of the patients in the low-risk group had evidence of disease after treatment. Patients classified as having no evidence of disease after treatment demonstrated significantly better EFI compared to those with evidence of disease. Conclusions: Our findings highlight the importance of meticulous risk stratification in predicting long-term outcomes and might serve as a basis for developing personalized therapeutic strategies. Identifying low-risk patients who may benefit from a less aggressive treatment approach while ensuring optimal treatment and follow-up for high-risk patients remains a central objective in the modern management of DTC.