BACKGROUND
Thyroid nodules are commonly discovered in clinical practice, either during physical examination or incidentally during various imaging procedures. The purpose of evaluating thyroid nodules is to determine which nodules are cancerous and require surgery. Ultrasound of the thyroid is very useful in evaluating thyroid nodules. There are 2 major ultrasound-based algorithms are currently being used to help risk-stratify the nodules: the American Thyroid Association (ATA) risk stratification system and the American College of Radiology Thyroid Image Reporting system (ACR-TIRADS). These ultrasound algorithms identify high-risk nodules that require further assessment with a thyroid biopsy. Once a nodule is biopsied, the results are reported in 1 of 6 risk categories ranging from benign to indeterminate to cancer.

Indeterminate biopsy results means the thyroid cells do not look clearly normal or abnormal and occurs in 10-15% of nodules. The uncertainty associated with indeterminate biopsy results can lead to unnecessary thyroid surgery. Companies have developed molecular tests to detect genes often present in cancerous cells to address this dilemma. One test called ThyroSeq™ can help identify those indeterminate nodules that are benign and thus do not need surgery.

This study examines whether combining results of molecular testing with ultrasound characteristics and other clinical variables could improve the accuracy of risk stratification of indeterminate thyroid nodules even more than is currently achieved through molecular testing or ultrasound alone.

THE FULL ARTICLE TITLE
Figge JJ et al. 2021 Do ultrasound patterns and clinical parameters inform the probability of thyroid cancer predicted by molecular testing in nodules with indeterminate cytology? Thyroid. Epub 2021 Sep 1. PMID: 34340592.

SUMMARY OF THE STUDY
The authors examined data from 257 nodules (from 232 patients) that a) were classified as indeterminate by thyroid biopsy, b) had molecular testing results with ThyroSeq™ and c) were surgically removed. For each nodule, the authors went back and examined the initial ultrasound images and assigned scores using both the ATA ultrasound risk stratification system and the ACR-TIRADS. Finally, they recorded clinical variables such as sex, age and family history of thyroid cancer. All this data was compared with the final diagnosis after surgery to see which variables improve the ability to predict thyroid cancer.

In nodules classified as indeterminate by thyroid biopsy, a positive ThyroSeq™ result was the strongest predictor of cancer. However, neither of the ultrasound scoring systems improved the ability to predict thyroid cancer, nor did any of the clinical variables that the authors examined. The results of this study suggest that, while ultrasound scoring systems are very helpful in identifying nodules that need to be biopsied, they cannot be used to decide if which nodules need to be surgically removed surgically when the result of the biopsy is indeterminate. When the biopsy result is indeterminate, the ThyroSeq™ molecular test is the best test to predict thyroid cancer.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that thyroid ultrasound is best used to select the thyroid nodules that need thyroid biopsy. This is because ultrasound can accurately determine which nodules need surgery and which nodules can be monitored most of the time. However, with indeterminate thyroid biopsy results, a molecular test such as ThyroSeq™ is the best test to predict which nodules are cancerous.

— Philip Segal, MD

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