BACKGROUND
Thyroid nodules are present in up to 65% of the general population, however, only 5-10% are cancerous. Thyroid biopsy is the best test available to differentiate between benign and cancerous thyroid nodules. The thyroid biopsy results are usually reported using the Bethesda System. This is a standardized reporting system with six categories, each category having a different cancer risk and specific recommendations for patient management: Bethesda I (nondiagnostic); Bethesda II (benign); Bethesda III (indeterminate – atypia of undetermined significance/ AUS); Bethesda IV (indeterminate – follicular neoplasm); Bethesda V (suspicious for cancer), and Bethesda VI (cancer).

The two indeterminate categories for malignancy, Bethesda III and IV, include specimens with abnormal thyroid cells that have a risk of cancer between the benign and cancer categories (10 to 40%). In the past, these thyroid nodules required surgical removal for a definitive diagnosis. More recently, molecular tests to identify cancer- related genes in the biopsy cells have been developed to further clarify the cancer risk of indeterminate thyroid nodules and avoid unnecessary surgery. Molecular tests have been confirmed to be effective in reducing unnecessary surgeries and they are also cost-effective in the management of thyroid nodules in Western countries.

In many Asian countries, molecular tests are expensive and not commonly used since they are not covered by insurance. In addition, a more conservative approach is preferred for indeterminate thyroid nodules. This is frequently done with active surveillance on ultrasound (following the nodules by ultrasound instead of up-front thyroid surgery). Surgery is also less expensive in the Asian compared to Western countries. The goal of this study is to evaluate whether it would be cost-effective to routinely use a commercially available molecular test — Thyroseq V3 — for the management of indeterminate thyroid nodules in Hong Kong.

THE FULL ARTICLE TITLE
Fung MHM et al. High rates of unnecessary surgery for indeterminate thyroid nodules in the absence of molecular test and the cost-effectiveness of utilizing molecular test in an Asian population: a decision analysis. Thyroid 2005;35(2):166-176; doi: 10.1089/thy.2024.0436. PMID: 39835971.

SUMMARY OF THE STUDY
The study evaluated 1957 thyroid biopsies performed at a single endocrine surgery center in Hong Kong between January 2018 and December 2021. Among these, 365 biopsies (19%) showed indeterminate results (Bethesda III or IV) with 36% of these patients opting for up-front surgery, 42% for repeat biopsy, and 22% for active surveillance on ultrasound. Molecular tests were not available for these patients. Among the patients who underwent up-front surgery, 28% were diagnosed with thyroid cancer, while 72% had benign thyroid nodules, thus the surgical intervention was unnecessary for these patients. The same thyroid cancer rates were noted in patients who underwent surgery later after first undergoing repeat biopsy or active surveillance on ultrasound.

A decision analysis based on the simulation of 10,000 patients over a two-year period was then used to evaluate the cost-effectiveness of indeterminate thyroid nodule management with and without molecular tests and determine the impact of these on costs and reduction in unnecessary surgeries. The routine use of molecular tests increased effectiveness by avoiding 26% more unnecessary surgeries as compared to the current model without molecular tests. However, this came with a higher average cost. The routine use of molecular tests would be cost saving, only with a cost less than the equivalent of $1,031.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Despite a more conservative approach with a lower rate of initial surgery than in the Western countries, the proportion of unnecessary surgical interventions for indeterminate thyroid nodules (Bethesda III/IV) remains high (72%) in an Asian population. Routine use of molecular testing can reduce the rate of unnecessary surgeries by 26%, however it is currently limited due to high cost. Molecular tests use would become cost-effective if the cost was substantially reduced.

— Alina Gavrila, MD, MMSc

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