Abstract

In differentiated thyroid cancers (DTC), iodine-131 (I-131) therapy is a cornerstone of treatment in combination with surgery. I-131 has long been routinely administered after thyroidectomy for remnant ablation, adjuvant therapy, or treatment of known residual or metastatic disease. However, accumulating evidence has demonstrated that in patients with a favorable prognosis and a low risk of residual or recurrent disease, routine I-131 therapy does not provide an additional survival benefit. Consequently, current clinical guidelines have introduced more selective criteria for patient eligibility for I-131 therapy. TNM classification system, which is widely used for staging thyroid cancer, is effective in predicting disease-specific survival but has limited utility in estimating the risk of residual or recurrent disease. To address this limitation, the American Thyroid Association developed an initial risk stratification system that incorporates histopathological and clinical features to better estimate recurrence risk. Also, response to therapy has emerged as a key prognostic factor. Dynamic risk stratification, based on post-treatment clinical, biochemical, and structural responses, allows reclassification of patients over time and supports individualized decisions regarding follow-up and additional therapy. Accordingly, treatment and surveillance strategies should integrate staging, risk stratification, imaging and laboratory findings, patient-related factors, healthcare system conditions, and, when available, molecular cytology, molecular pathology, and molecular imaging data. Although current guidelines share common principles regarding risk assessment and I-131 therapy, full consensus has not been achieved. There is universal agreement that I-131 is indicated for patients with high-risk features or metastatic disease. In contrast, I-131 has not been recommended for many years in low-risk DTC patients with intrathyroidal tumors ≤1 cm and no additional adverse features. The role of I-131 in other low- and intermediate-risk patient groups remains controversial, with notable differences among guidelines. This review summarizes initial and dynamic risk stratification approaches in DTC and examines current guideline-based indications for I-131 therapy.