Management of Indeterminate Thyroid Nodules: A Model Comparing Surgery, Molecular Testing, and Observation.

Objective: Optimal management of indeterminate nodules remains a controversial area of endocrine surgery. The purpose of this study is to compare observation, molecular testing, and immediate thyroid surgery for the management of Bethesda Classes III and IV nodules in patients age 50 to 90 years.

Study Design: A decision analysis was performed from April 22, 2021, to September 29, 2023, using a Markov model constructed with TreeAgePro 2023. Model variables and ranges were selected based on literature review data.

Setting: TreeAgePro.

Methods: A 1-way sensitivity analysis was performed to evaluate the age threshold at which each management pathway, immediate thyroid surgery, additional molecular testing, or observation, would be favored. A Monte Carlo probabilistic sensitivity analysis was performed 5 times with model patients assigned starting ages of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would impact model results. Outcomes were measured with quality-adjusted life-years and accounted for perioperative complications including permanent recurrent laryngeal nerve injury, permanent hypoparathyroidism, and medical complications.

Results: In the study models, molecular testing was more beneficial than surgery and observation across all ages. The age threshold at which observation became more beneficial than surgery as the next best option was 83.1 years. However, the clinical difference between all 3 treatment algorithms was relatively minimal.

Conclusions: Decision-making regarding indeterminate thyroid nodules is complex. Given the clinically similar results across all 3 treatment algorithm, this study reinforces that treatment modalities should be individually tailored and based on shared physician-patient decision making.