Gene expression test reduced decision to operate on indeterminate nodules

Implementing a new gene expression test in the diagnosis of patients with thyroid nodules with indeterminate fine-needle aspiration cytology could result in the potential avoidance of tens of thousands of surgeries per year in the United States, according to Bryan McIver, MD.

“It has been shown that up to 50% of adult women have a nodule in her thyroid gland, and one out of every four men over the age of 50 has a lump in his thyroid gland. So these things are incredibly common beyond the age of 50. In fact, in women it is normal to have a lump in her thyroid gland,” McIver told Endocrine Today.

“The rates at which we are diagnosing thyroid cancer are going up as well. While the majority of thyroid nodules are benign, the number of cancers we are finding is going up very significantly,” he said.

McIver, of the department of medicine at the Mayo Clinic in Rochester, Minn., and other researchers sought to evaluate how the Afirma gene expression classifier (AGEC) affected the decision of endocrinologists and their patients on whether to operate when fine-needle aspiration (FNA) cytology was indeterminate and the AGEC reading of the nodule was benign.

The diagnostic test was developed by Veracyte. The assay identifies nodules as either benign or suspicious for malignancy.

The researchers conducted a cross-sectional cohort study with data contributed retrospectively by 51 endocrinologists at 21 practice sites that had previously obtained more than three benign AGEC readings in nodules larger than 1 cm with indeterminate FNA cytology readings.

“This is a test that I’m excited about. It has great potential to improve the health of our patients, and that is what we are all in this business for,” McIver said.

Historically, the rate of surgery for cytologically indeterminate nodules was 74% vs. a decrease to 7.6% during the period that AGEC readings were taken in clinical practices, researchers wrote.

The rate of surgery on cytologically indeterminate nodules ruled benign by the AGEC reading was no different from the historically reported rate of operation on cytologically benign nodules (P=.41).

Physicians reported four primary reasons for operating on nodules with a benign AGEC reading:

• Large nodule size; 46.4%.
• Symptomatic nodules; 25%.
• Rapidly growing nodules; 10.7%.
• Second suspicious or malignant nodule in the same patient; 10.7%.

“Before this test was available, roughly 90% of everybody who had an indeterminate biopsy would go to the operating room. What we were able to show was when that test was used, we could turn that around, and less than 10% of the patients went to the operating room instead,” McIver said.

In the past 40 years, McIver said various indeterminate biopsy results led many patients to the operating room. In those cases of indeterminate biopsy, less than one in six turns out to be cancer, whereas the remaining five of six turns out benign.

“[After biopsy] we tell the patient there’s good news; it wasn’t cancer, and the patient is generally happy about that. In the meantime, we’ve done, in reality, what was probably an unnecessary surgery. If we had known it was benign, we wouldn’t have needed to do anything. We’ve exposed our patient to the risk of the surgery and the anesthetic, and increased the chance that they will need thyroid hormone treatment in the future because we’ve removed 50% of their thyroid gland,” McIver said.

“If what we found in our study translates across the country as a whole, and I have no reason to think that it won’t, then we are talking about tens of thousands of surgeries that can be avoided per year in the US and saving millions of dollars in the health care system. So it is dramatic,” he said.

Disclosure: Dr. McIver reports no relevant financial disclosures. The study was funded by a research grant provided by Veracyte to the institutions of Drs. Duick and Klopper. Ms. Friedman and Drs. Diggans, Kennedy and Lanman are employees of Veracyte.