Moderate THST Improves Outcomes in Differentiated Thyroid Cancer

Aubrey A. Carhill, MD

Long-term moderate thyroid hormone suppression therapy (THST) is associated with improved outcomes in patients with differentiated thyroid cancer (DTC), according to data from 1987 to 2012 presented by Aubrey A. Carhill, MD, on behalf of the National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG) registry analysis.

"In the absence of prospective studies detailing the ultimate longitudinal effects of initial and long-term therapy for patients with differentiated thyroid cancer, clinicians have had to rely on retrospective studies and expert opinion,” said Carhill, as Assistant Professor in the Endocrine Neoplasia and Hormonal Disorders group at the University of Texas, MD Anderson Cancer Center in Houston. “Consequently, debate remains as to the appropriate extent of surgery, post-operative radioiodine, and thyroid-stimulating hormone-suppressive therapy."

The NTCTCSG registry prospectively collects data related to clinical outcomes from multiple institutions following treatment of patients with DTC. The predictive value of the NTCTCSG Registry clinicopathologic staging system for thyroid cancer, which uses patient age at diagnosis, tumor size and histology, and differentiation, metastases, intrathyroidal multifocality, and extraglandular invasion, has been consistently shown to be among the highest for disease-free survival (DFS) and overall survival (OS).

The registry data showed that stage III patients who received RAI (relative risk [RR] 0.66, P = .04) and stage IV patients who received both total/near-total thyroidectomy (T/NTT) and RAIs (RR 0.66 and 0.70, combined P = .049) exhibited improved OS. Patients of all stages exhibited significantly improved OS (stage I-IV: RR=0.13, 0.09, 0.13, 0.33, respectively) and DFS (stage I-III: RR=0.52, 0.40, 0.18, respectively) with moderate THST but not aggressive THST treatment. Furthermore, when distant metastatic disease was diagnosed in long-term follow-up, moderate THST was associated with significantly improved OS, and moderate THST and lower initial disease stage were independently predictive of improved OS. In follow-up of patients who were rendered disease free after initial therapy, moderate THST was shown to be independently predictive of DFS for at least the first 3 years of follow-up.

In multivariate analysis of primary treatments for DTC, in all stages, only THST was associated with both improved OS and DFS. Like others, this study has its limitations, including institutional bias, assignment of disease status at entry, treatment selection, and others. However, when examining the degree of THST, aggressive THST confers no additional survival advantages as compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease.

"This registry update increases by more than 2,000 the number of patients followed to 4,941 in the overall cohort and 3,238 patients in the THST cohort, with a mean follow-up time of 6 years," Carhill said. Since the last registry update in 2001 with data from 14 institutions, the registry now includes a total of 34,631 person-years of documented follow-up time with some patients followed for as long as 25 years. For all registry patients, the effects of initial therapies, including thyroidectomy and radioactive iodine (RAI), as well as long-term THST were documented, the NTCTCSG staging system was applied, and OS and DFS were assessed. Moderate THST was defined as a TSH level in the subnormal to normal range, while aggressive THST was defined as a TSH level maintained in the undetectable to subnormal range.

"We confirm previous findings that T/NTT followed by RAI is associated with survival benefit in high-risk but not low-risk patients. In contrast with our earlier reports, only moderate THST is associated with better outcomes in all stages, including low-risk stage I patients, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow up," she said. "The challenge for clinicians is to balance the benefits and risks of treatment. Moderate THST continued at least 3 years after diagnosis may be indicated in higher risk patients," Carhill concluded.

Reference

Carhill A, Litofsky DR, Ain K, Brierley J, Cooper DS, Fein, H, et al. Long-term moderate thyroid hormone suppression therapy is associated with improved outcomes in differentiated thyroid carcinoma: national thyroid cancer treatment cooperative study group registry analysis 1987—2012. Presented at: the 84th Annual Meeting of the American Thyroid Association; October 29-November 2, 2014; Coronado, CA.Clinical Oral Abstract #11.

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