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Molecular Testing of Bethesda III/IV Thyroid Nodules: A Cost-Effectiveness Analysis

Nicholson KJ, Roberts MS, McCoy KL, Carty SE, Yip L


Molecular tests (MT) using gene expression and/or mutational analysis have been developed to reduce the need for diagnostic surgery for indeterminate (Bethesda III/IV) thyroid nodules. Prior cost effectiveness studies have shown mixed results but none have included the recent and more comprehensive versions of the 2 commonly utilized MT. The aim of this study is to compare the cost-effectiveness of diagnostic lobectomy (DL), the Afirma Gene Sequencing Classifier (GSC), and Thyroseq Next-Generation Sequencing version 3 (TSv3).


A decision tree from the payer perspective was created using a base case of a 40-year-old euthyroid woman with a solitary 2 cm Bethesda III or IV thyroid nodule. In this model, all patients in the DL arm had lobectomy, which was also performed for patients with positive MT, while those with negative MT underwent 20 years of surveillance. The outcome was a correct diagnosis, defined as malignant histology after DL or 20 years of nodule stability after negative MT. Costs were obtained from CMS data and existing literature, and probabilities were obtained from the literature. Sensitivity analysis was performed for costs, pre-test probability of malignancy, and performance parameters.


The cost per correct diagnosis was $14,277 for TSV3, $17,873 for GSC, and $38,408 for DL. TSv3 was preferred over both GSC and DL. One-way sensitivity analysis between TSv3 and GSC demonstrated that the results were robust to variations in cost, cancer prevalence, and length of surveillance. In two-way sensitivity analysis, TSv3 was preferred over GSC at all considered test costs, and in probabilistic sensitivity analysis, TSv3 was the preferred management strategy in 68.5% of cases.


In hypothetical modeling to determine whether surgery versus MT is optimal for indeterminate (Bethesda III/IV) nodules, either of the major molecular tests was considerably more cost-effective than diagnostic lobectomy, although TSv3 was more likely to be cost-effective than GSC. Use of either MT adjunct should be strongly considered in the absence of other indications for thyroidectomy.



Thyroid. 2019;

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