Clinical and Histopathological Risk Factors for Radioactive Iodine-Refractory Follicular and Oncocytic Thyroid Carcinoma

Context Risk factors for radioactive iodine (RAI)-refractory disease in follicular (FTC) and oncocytic thyroid carcinoma (OTC) are unknown.Objective The aim of this study is to identify clinical and histopathological risk factors for RAI-refractory disease in FTC and OTC patients, facilitated by an extensive histopathological revision.Methods All adult FTC and OTC patients treated at Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. The 2015 American Thyroid Association guidelines were used to define RAI-refractory disease. An extensive histopathological revision was performed applying the 2022 World Health Organization Classification using PALGA, the Dutch Pathology Databank. Logistic regression was used to identify risk factors for RAI-refractory disease, stratified by histological subtype.Results Ninety FTC and 52 OTC patients were included, of whom 14 FTC (15.6%) and 22 OTC (42.3%) patients developed RAI-refractory disease over a follow-up time of 8.5 years. RAI-refractory disease occurred in OTC after fewer cycles than in FTC (2.0 [interquartile range (IQR): 1.0-2.0] vs 2.5 [IQR: 2.0-3.75]), and it substantially decreased 10-year disease-specific survival, especially in OTC (46.4%; FTC 85.7%). In FTC, risk factors were higher age at diagnosis, pT3/pT4 stage, N1 stage, widely invasive tumors, and extrathyroidal extension. N1 stage and M1 stage were the strongest risk factors in OTC, rather than histopathological characteristics of the primary tumor.Conclusion To our knowledge, this is the first study that correlates clinical and histopathological risk factors with RAI-refractory disease in FTC and OTC, facilitated by a histopathological revision. In FTC, risk factors for RAI-refractory disease were foremost histopathological characteristics of the primary tumor, whereas in OTC presentation with lymph node and distant metastasis was associated with RAI-refractory disease. Our data can help clinical decision-making, particularly in patients at risk for RAI-refractory disease.