Less is more? Evaluating the role of radioiodine therapy in pediatric differentiated thyroid cancer management

Abstract

Purpose: Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy in children and adolescents. Pediatric DTC often presents with extensive nodal disease or pulmonary metastases, yet disease-specific survival consistently exceeds 95-98%. This paradox challenges the historical practice of routine postoperative radioiodine (RAI) therapy, especially in low-risk children who may derive little oncologic benefit while remaining vulnerable to lifelong radiation-related harm. To critically evaluate whether routine RAI remains justified in pediatric DTC, using a PICO-based narrative review focused on oncologic efficacy, long-term toxicity, risk-adapted indications, and emerging alternatives. Methods: A narrative review of 37 studies published between 2000 and 2025 was conducted, including pediatric cohorts, registry analyses, meta-analyses, and international guidelines. Eligible studies involved patients younger than 18 years with DTC and reported RAI-related outcomes, including remission, recurrence, survival, biochemical or structural response, and treatment-related toxicity. Results: RAI appears most beneficial in selected intermediate- and high-risk patients, particularly those with iodine-avid pulmonary metastases. Conversely, low-risk children generally achieve excellent outcomes with surgery alone, without a demonstrated survival advantage from routine adjuvant RAI. Reported toxicities include salivary dysfunction, marrow suppression, gonadal impairment, second primary malignancies, and rare fatal pulmonary fibrosis. Contemporary ATA and ETA recommendations, supported by registry data, confirm a marked shift away from routine RAI toward individualized treatment. Conclusion: RAI remains indispensable for selected high-risk pediatric DTC, but its universal use is no longer defensible. In modern pediatric thyroid cancer care, a risk-adapted "less is more" strategy offers the most rational balance between cure and long-term safety.