Radioiodine Treatment of Metastatic Thyroid Cancer: Relative Efficacy and Side Effect Profile of Preparation by Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin

Background: To effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum thyrotropin (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The aim of our study was to compare the relative efficacy and side effect profile of rhTSH versus THW preparation for RAI therapy of metastatic DTC. Methods: Fifty-six patients (31 women and 25 men) with RAI-avid distant metastases of DTC treated with either rhTSH-aided (n = 15) or THW-aided RAI (n = 41) and followed for 72 +/- 36.2 months were retrospectively analyzed. The groups were comparable in regard to mean size of target lesions (rhTSH vs. THW 6.4 vs. 4.8 cm, p = 0.41), mean baseline thyroglobulin level (6995 vs. 5544 ng/mL, p = 0.83), distribution of micronodular and macronodular pulmonary metastases (67% vs. 63%, p = 0.54, 13% vs. 15% p = 0.64, respectively), osseous (53% vs. 29%, p = 0.09), brain (0% vs. 2%, p = 0.73), and liver/kidney metastases (13% vs. 2%, p = 0.61). Patients in the rhTSH group were older (rhTSH vs. THW mean 62 vs. 49 years, p = 0.01), and received lower cumulative RAI dose (256 vs. 416 mCi, p = 0.03), which was more frequently based on dosimetric calculations (80% vs. 46%, p = 0.024). Responses to treatment were based on RECIST 1.1 criteria. Results: Adjusted by age rates of complete response (CR), stable disease (SD), progressive disease (PD), and progression free survival (PFS) were not different between the groups (rhTSH vs. THW CR hazard ratio [HR] 0.97, 95% CI 0.08-11.42, p = 0.982; SD HR 3.22, 95% CI 0.79-13.18, p = 0.104, PD HR 0.26, 95% CI 0.52-1.26, p = 0.094; PFS HR 0.41, 95% CI 0.14-1.23, p = 0.112). The only independent risk factor for nonresponding to treatment and presentation with PD was age (HR 1.06, 95% CI 1.02-1.11, p = 0.008). Age was also an independent factor affecting PFS (HR 1.04 for each year, 95% CI 1.02-1.07, p = 0.001). Rates of leukopenia, thrombocytopenia, xerostomia, and restrictive pulmonary disease after RAI were not significantly different (rhTSH vs. THW 30% vs. 28%, p = 0.61, 10% vs. 0%, p = 0.37, 0% vs. 12%, p = 0.20, 0% vs. 2%, p = 0.73, respectively). Conclusions: Patients with metastatic DTC prepared with rhTSH achieve comparable benefit of RAI therapy as those treated after THW.