Endocrine Abstracts

Introduction: Historically, treatment of follicular thyroid carcinoma (FTC) and oncocytic thyroid carcinoma (OTC) is based on thyroidectomy followed by radioiodine (RAI) therapy. Both tumor types have a good prognosis (10-year survival 80-94%), but this changes significantly once RAI-refractory disease occurs (median 3.5 years), which limits further treatment possibilities. The main risk factors for developing RAI-refractory disease in FTC and OTC are unknown. Our aim was to identify clinicopathological risk factors for developing RAI-refractory disease in FTC and OTC patients, facilitated by an extensive histopathological revision.

Methods: All adult FTC and OTC patients treated at the Erasmus MC between 2000 and 2016 were retrospectively included (n =142). The 2015 ATA Guidelines were used to define RAI-refractory disease. An extensive histopathological revision was performed independently by two pathologists, applying the 2022 WHO Guidelines. Risk factors were identified using logistic regression, and a sensitivity analysis on histological subtype was performed to distinguish between FTC and OTC.

Results: Of the 142 included patients, 36 became RAI-refractory (25.4%; n =16 FTC) over a median follow-up time of 8.5 years [IQR: 5.0-11.4]. Patients developed RAI-refractory disease after a median of 2 years [IQR: 0.9-4.4] and 2 therapies [IQR: 2-3] after initial diagnosis. RAI-refractory disease was mostly diagnosed based on the criterion of disease progression despite sufficient RAI dosage (38.9%). Patients with refractory disease had a significantly worse 10-year survival than the RAI-sensitive group (62.4% vs 95.9%; P < 0.001). Clinical risk factors were higher age at diagnosis (OR 1.05; 95%CI 1.02-1.08) and presentation with distant metastasis (OR 4.99; 95%CI 2.03-12.3). Histopathological risk factors were ≥4 foci of vascular invasion (OR 8.13; 95%CI 2.58-25.6), no encapsulation (OR 6.83; 95%CI 2.76-16.9), extra-thyroidal extension (OR 5.43; 95%CI 2.12-13.9) and oncocytic cell metaplasia (OR 3.98; 95%CI 1.80-8.79). Results remained unchanged after correction. Compared to FTC, presentation with distant metastasis was the strongest risk factor in OTC patients for RAI-refractory disease, rather than classical histopathological features.

Conclusion: To our knowledge, this is the first study that extensively revises histopathology in a large cohort of FTC and OTC patients, and that correlates clinical and histopathological risk factors with development of RAI-refractory disease. Age at diagnosis, distant metastasis at presentation and tumors showing no encapsulation, extensive vascular invasion or oncocytic cell metaplasia are risk factors for RAI-refractory disease. Our data can aid clinical decision making, particularly in those who have a high probability to develop RAI-refractory diseases, such as patients with OTC presenting with distant metastasis.