Molecular Testing Versus Diagnostic Lobectomy in Bethesda III/IV Thyroid Nodules: A Cost-Effectiveness Analysis

Abstract

Background: 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 has included the recent and more comprehensive versions of the two 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 version 3 (TSv3). Methods: 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 the Centers for Medicare & Medicaid Services (CMS) data and existing literature, and probabilities were obtained from the literature. Sensitivity analysis was performed for costs, pretest probability of malignancy, and performance parameters. Results: 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 the 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. Conclusions: In hypothetical modeling to determine whether surgery versus MT is optimal for indeterminate (Bethesda III/IV) nodules, either of the major MT was considerably more cost-effective than DL, 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.

Keywords: Bethesda III/IV nodule; cost-effectiveness; diagnostic lobectomy; molecular testing; thyroid nodule.

FIG. 1.

Decision tree used to compare rates of correct diagnosis for DL, TSv3, and GSC (16). 1: effectiveness of optimal management, 0: effectiveness of nonoptimal management. In the Markov model, remaining in the “Well” category at the conclusion of the model results in an effectiveness value of 1, while transitioning to the “Detect cancer” or “Dead” states at any time results in an effectiveness of 0. DL, diagnostic lobectomy; GSC, Gene Sequencing Classifier; TSv3, ThyroSeq version 3.

FIG. 2.

Tornado diagram: one-way sensitivity analysis of incremental cost-effectiveness of TSv3 over GSC. Black bars represent higher parameter values and gray bars represent lower parameter values. Values on x-axis represent cost savings per correct diagnosis of TSv3 over GSC.

FIG. 3.

Probabilistic sensitivity analysis: cost-effectiveness scatter plot demonstrating cost and probability of correct diagnosis over 10,000 iterations with simultaneous variation of input values. Circle: diagnostic lobectomy; triangle: GSC; square: TSv3.