Indeterminate Thyroid Nodule Management: Comparing Surgery, Molecular Testing, and Observation

Introduction: Optimal management of indeterminate nodules remains a controversial area of thyroidology. The purpose of this study is to compare 1) observation, 2) molecular testing, or 3) immediate thyroid surgery for the management of Bethesda Class III and IV nodules in patients 50 and older.

Methods: A decision analytical model was performed from April 22, 2021 to January 25, 2023 using a Markov model constructed with TreeAgePro 2021. Model variables and ranges were selected based on literature review data. Observation consisted of annual ultrasound surveillance, in which nodules with greater than 20% growth in size underwent hemithyroidectomy with subsequent completion total thyroidectomy if malignant. Molecular testing efficacy values were obtained, and those with positive results underwent thyroidectomy. Immediate surgery involved upfront total thyroidectomy. A one-way sensitivity analysis was performed. A Monte Carlo probabilistic sensitivity analysis was performed 5 times with patients assigned starting ages of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would impact results. Outcomes were measured with quality-adjusted life-years (QALYs) and accounted for complications including perioperative recurrent laryngeal nerve injury and permanent hypoparathyroidism, cancer-related death, perioperative morbidity and death, and unrelated death.

Results: Among patients diagnosed between 50-90 years of age, surgery provided the best outcomes followed by observation then molecular testing. However as age at diagnosis increased, the benefit of surgery over observation and molecular testing decreased (50 years: observation= -0.91 QALYs, molecular testing= -0.039 QALYs; 90 years: observation= -0.65 QALYs, molecular testing= -0.16 QALYs).

Conclusions: Optimal management of indeterminate thyroid nodules remains challenging, and may include upfront surgery, molecular testing, or observation. While immediate surgery may offer superior outcomes, its favorability relative to observation and molecular testing may be less pronounced among older patients.