On-demand L-thyroxine replacement therapy in post-lobectomy papillary thyroid cancer: a prospective non-randomized controlled study

Background: The necessity of thyrotropin (TSH) suppression therapy for papillary thyroid cancer (PTC) after lobectomy has been challenged. This study aims to evaluate on-demand L-thyroxine replacement therapy for post-lobectomy PTC. Methods: This prospective study cohort included adult patients with low- to intermediate risk PTC, who underwent lobectomy (2021-2023). L-thyroxine supplementation was given after surgery only if serum TSH exceeded the upper limit of reference range (>5.91 mU/L). Retrospective controls were selected from the institute database (2000 to 2014) after matched with prospective patients and treated according to guideline (TSH, 0.5-2 mU/L). The primary endpoint was prognosis, including structural recurrence and biochemical response. Secondary endpoint was the euthyroidism rate without thyroxine. Kaplan-Meier curve was used to estimate RFS and euthyroidism rates, and compared using the log-rank test. Results: Among 381 patients who were enrolled in the present study [median age 39 years, 70.6% female], no new cases were detected requiring L-thyroxine for elevated TSH at greater than year post surgery. In the prognostic evaluation, 333 cases were included, with a mean follow-up of 17 months, 72.3% never underwent L-thyroxine supplementation. Comparison with the historical control group was conducted in 204 pairs of cases. No significant difference was observed in either 2-year RFS (test group vs. control group, 99.4% vs. 98.5%, P = 0.917) or biochemical responses among patients with negative thyroglobulin antibody (rate of patients with increasing thyroglobulin, 21.6% vs 21.6%, P>0.05). Conclusions: On-demand L-thyroxine replacement therapy benefit three-fourths of post-lobectomy low- to intermediate-risk PTC patients avoid L-thyroxine supplementation, while preserving equivalent short-term treatment response and RFS.