A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol

Abstract

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate-and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The followup period is 5 years. Conclusion:The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Outcomes and Trends of Treatments in High‐Risk Differentiated Thyroid Cancer

“…14,43 Recently, however, some studies have suggested that such low levels of thyroidstimulating hormone may not only have a nonsignificant impact on survival and tumor recurrence but may actually be counterproductive to a patient's quality of life due to THST's associated cardiovascular and metabolic adverse effects. 35,44,45 Hence, in 2015, the ATA revised its guidelines on THST to primarily recommend thyroid-stimulating hormone suppression in certain high-risk cases, providing a potential explanation for the observed trend reversal in THST usage that seemingly began in 2015. 46 Although a relatively more subtle change than that of THST, a mild decrease in RAI usage was observed during the study years.…”

“…Additionally, in 2009, the ATA released a revision of its guidelines that expanded the candidacy for thyroid‐stimulating hormone suppression therapy, where patients at low/intermediate risk and high risk were recommended to maintain thyroid‐stimulating hormone levels of 0.1‐0.5 mU/L and <0.1 mU/L, respectively, as opposed to 0.3‐2.0 mU/L and 0.1‐0.5 mU/L, as previously advised by 2006 guidelines 14,43 . Recently, however, some studies have suggested that such low levels of thyroid‐stimulating hormone may not only have a nonsignificant impact on survival and tumor recurrence but may actually be counterproductive to a patient's quality of life due to THST's associated cardiovascular and metabolic adverse effects 35,44,45 . Hence, in 2015, the ATA revised its guidelines on THST to primarily recommend thyroid‐stimulating hormone suppression in certain high‐risk cases, providing a potential explanation for the observed trend reversal in THST usage that seemingly began in 2015 46 …”

The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research

“…Thyroid cancer recurrence, complications, and quality of life were compared as measures of effectiveness between the two interventions. Furthermore, researchers at the Korean Thyroid Association launched a practical clinical trial (the Multicenter Randomized Controlled Study for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid lobEctomy in Low to Intermediate Risk Thyroid Cancer Patients [MASTER] study) for thyroid cancer patients who underwent lobectomy for low-risk and intermediate-risk cancer to compare recurrence, quality of life, and complications (including cardiovascular disease, osteoporosis, and metabolic disease, and musculoskeletal disease) [ 46 ]. For the first study, if the effects of the two interventions are the same, the economic benefit can be evaluated through CMA.…”

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)

“…Patients were selected from the cohort of the MASTER study, the protocol of which was detailed previously [ 12 ]. Inclusion criteria were as follows: (1) male or nonpregnant female aged between 19 and 79 years old, (2) biopsy-proven papillary thyroid cancer (PTC) requiring TL, (3) no gross extrathyroidal extension to adjacent structures (nerve, vessel, trachea, etc.)…”

“…The randomization was finalized prior to the postoperative 2-week follow-up visit, at which point the dosage adjustment began. Patients received thyroid function tests as part of a routine clinical assessment at every visit, and LT4 dosages were adjusted when the TSH levels were out of target ranges, according to our previously determined adjustment protocol [ 12 ].…”