Association of Free Thyroxine with Progression-Free Survival in Intermediate and High Risk Differentiated Thyroid Cancer

Abstract Context Supraphysiologic T4 doses are used in intermediate- and high-risk patients with differentiated thyroid cancer (IR/HR-DTC) to suppress tumor progression by TSH. However, preclinical data suggest that T4 can also act as a growth stimulus for cancer, but there is no clinical evidence supporting this claim. Objective We analyzed the association between free T4 (FT4) and progression-free survival (PFS) in patients with IR/HR-DTC. Methods This longitudinal cohort study, approved by multi-institutional review board, included patients with IR/HR-DTC treated uniformly with total thyroidectomy, radioiodine, and TSH suppression therapy, with at least 3 TSH and FT4 values available. Association between FT4 and PFS at landmarks 6, 12, and 18 months was assessed by Kaplan-Meier survival curves, whereas competing risks were assessed through Cox proportional hazards model. Results From 739 screened patients, 382 met the inclusion criteria and were characterized by a median age of 46 (34-59) years, 64.1% women, and treated with a median radioiodine dosage of 159 (110-410) mCi. During follow up of 7.1 (3.4-12.7) years, 34.6% experienced disease progression. Elevated FT4, observed in 29.3% of patients, was not associated with worse PFS (hazard ratio [HR], 0.9; CI, 0.54-1.5; P = .69), whereas age (HR, 1.02; CI, 1.004-1.04; P = .01), tumor size (HR, 1.15; CI, 1.04-1.28; P = .01) and metastases to the lateral neck lymph nodes (HR, 2.9; CI, 1.7-4.74; P < .001), bones (HR, 4.87; CI, 1.79-13.3; P = .002), and brain (HR, 5.56; CI; 2.54-12.2; P < .001) were associated with shorter PFS. Conclusion Contrary to preclinical evidence, elevated FT4 levels do not affect PFS in patients with IR/HR-DTC.