Each year in the U.S, approximately 75,000 patients undergo surgery to remove cytologically indeterminate thyroid nodules—small growths of cells near their thyroid gland that can’t be classified as benign or malignant with a traditional biopsy.
But UC professor of otolaryngology and endocrinology David Steward, MD, recently participated in a study that could exclude up to a third of those patients from surgery by using a new gene-expression test to rule out malignancy.
"Currently, a fine needle biopsy conducted on a thyroid nodule has a 20 percent chance of coming back indeterminate--containing suspicious or aytpical cells--and a 20 percent risk of malignancy,” says Steward. "Most patients with indeterminate nodules are referred for diagnostic surgery, which removes the side of the thyroid with the nodule to make a definitive diagnosis.”
But Steward, who also practices clinically as a UC Health otolaryngologist, says the majority of indeterminate nodules turn out benign—and for those patients, even the minor surgery exposes them to a risk of complications, including damage to the nerves of the vocal cords causing hoarseness, or the need for hormone replacement therapy.
"Our overriding goal is to minimize the number of diagnostic or unnecessary thyroid surgeries,” he says.
In the study, otolaryngology and endocrinology experts evaluated a new gene-expression classifier that measures the expression of 167 genes in the sample cells for mutations suspicious of malignancy.
The test was performed on 265 cytologically indeterminate thyroid nodule samples from 49 sites across the country, comparing the results of the gene-expression test against the results of physician-recommended biopsies. Thyroid surgery was performed on the basis of the clinical judgment of the treating physician at each site, without knowledge of the results of the gene-expression classifier.
Of the nodules tested in the study, the classifier correctly identified the benign nodules with a negative predictive value of 95 percent.
"To be of best use for clinicians, the test needed to have a high sensitivity and high negative predictive value for benign nodules,” says Steward. "This trial validated the usefulness of the gene-expression classifier for those patients.”
Steward says he’s already incorporated the test into his clinical practice, and it could provide a new model for managing these nodules in a clinical setting. With a more reliable way to classify indeterminate samples, more patients can avoid a thyroid surgery.
"This can be a very significant new option for some patients,” he says. "If the gene-expression classifier finds no suspicious mutations, the risk of malignancy is reduced to fewer than 5 percent and we can recommend watchful monitoring.”
Steward cautions that the test is not useful for all patients, as management of thyroid nodules requires an ongoing discussion between physicians and patients. Patients with a family history of thyroid cancer or history of radiation exposure, for example, may still need surgery for a full evaluation of the nodule.
The trial was sponsored by VeraCyte, Inc. Steward reports no financial interest in the company.