Prognostic Factors in Lenvatinib-Treated Differentiated Thyroid Cancer: A Real-World Study with Extended Follow-Up

Background Lenvatinib is a standard first-line treatment for progressive radioiodine-refractory differentiated thyroid cancer (RAI-R DTC), but real-world outcomes over extended follow-up and prognostic factors remain insufficiently characterized. Methods We retrospectively analyzed 97 patients with progressive RAI-R DTC treated with lenvatinib at a single institution between 2015 and 2024. Patients with anaplastic or medullary thyroid carcinoma and those treated for less than six months were excluded. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards models. Results Median age at treatment initiation was 68 years, and 38% of patients had bone metastases. With a median follow-up of 36 months, median PFS and OS were 25 months (95% confidence interval [CI], 21–31) and 59 months (95% CI, 45–82), respectively. The objective response rate was 58%, and the disease control rate was 97%. Multivariate analysis identified older age as an independent predictor of shorter PFS (Hazard ratio [HR] 1.34 per decade of age, p<0.01) and OS (HR 1.63 per decade of age, p<0.005). Bone metastasis was independently associated with worse OS (HR 2.25, p<0.05) but not PFS. Receiver operating characteristic analyses suggested age cutoffs of approximately 70 years. Bone metastasis was associated with significantly poorer OS among older patients. Conclusions Lenvatinib provided durable disease control in patients with RAI-R DTC. Older age at treatment initiation and bone metastasis were independent determinants of survival and may help guide risk stratification and treatment timing in clinical practice.