Gene Classifier 'Great Rule-Out Test' for Thyroid-Nodule Surgery

Miriam E Tucker

May 10, 2017

AUSTIN, Texas — Use of a commercially available gene-expression classifier (GEC) for indeterminate thyroid nodules results in about one-third fewer patients undergoing surgery and significant cost savings at 6 years, a new study suggests.

Results from a single-center study of the Afirma (Veracyte) (GEC)  were presented May 7 here at the American Association of Clinical Endocrinologists (AACE)  2017 Annual Scientific & Clinical Congress by Brian E Michael, MD, an endocrinologist formerly with Wellspan Health, Gettysburg, Pennsylvania.

In up to 6 years of follow-up so far, none of 16 nodules deemed benign by the GEC have developed malignancies and only three of those patients have undergone surgery for other reasons.

The new study is believed to be the longest follow-up to date of thyroid nodules analyzed with the Afirma GEC, which is licensed for clinical use with indeterminate fine-needle aspiration specimens.

It is designed to help physicians decide which of those patients can be safely monitored rather than sent for surgery; the latter costs between $12,000 and 15,000 per procedure, Dr Michael said.

"This is reassuring data that nothing bad is likely to happen with routine clinical follow-up," Dr Michael told Medscape Medical News, noting that patients still need to be followed with regular physical exams and ultrasounds at guideline-recommended intervals. But if that is carried out, "you certainly won't miss a lot of cancers....It's a great rule-out test."

However, session moderator David Lieb, MD, associate professor of internal medicine and program director of the endocrinology fellowship program at Eastern Virginia Medical School, Norfolk, cautioned that the performance of any of the GECs currently on the market can vary by location.

"We're hearing more and more about different molecular diagnostic tests. They have different characteristics. I think it's really important when you're choosing whether to use one of these tests to go to the literature and understand how and where the test was validated and what the population was like."

Doctors will then be able to determine for themselves whether the patients they are seeing where they live "match well enough to the patients that were studied," he observed.

The Gettysburg, Pennsylvania center is one of several sites nationwide for which pooled 3-year data were previously reported (Endocr Pract. 2016;22:666-672).

Although the combined data are useful, Dr Lieb said, "rates of malignancy differ around the country…..Veracyte has very good negative predictive value, but you have to know the prevalence of disease where you are, because that's part of the calculation."

Test Performs Well in Long-term Follow-up

Dr Michael began using Afirma as soon as it became available, and his data collection spanned the first 26 months that it entered the US market. A total of 447 individual thyroid nodules >1 cm in size were evaluated between January 2011 and March 2014.

Of those, GEC was successfully run on preserved RNA samples from 44 nodules with indeterminate cytology. Of those, 28 specimens were deemed suspicious and the patients referred for surgery, while the other 16 patients with nodules classified as benign were followed with physical exam and ultrasound at 6 months post–initial biopsy and annually thereafter.

Of those 16, three underwent surgery within the first year — one was for a large symptomatic nodule with benign histopathology, and another, in a pregnant woman, was for a nodule that was also benign but was rapidly enlarging and symptomatic. The third surgery was in a patient who had two nodules, one that had been deemed benign by GEC and the other suspicious. On final pathology, the GEC had been correct on both counts.

Of the remaining 13 GEC-benign patients who did not undergo surgery, six have been followed for 5 to 6 years, four for 3.5 to 5 years, and three for 3 to 3.5 years.

Thus far, they've all remained asymptomatic and physically stable, with serial ultrasounds showing no changes in appearance, volume, or other characteristics of the nodules under surveillance.

Preventing Surgery, Saving Money?

Thus, Dr Michael said, "37% of patients in this indeterminate group who previously would have been referred for surgery have been observed using Afirma/GEC results for guidance. Long-term follow-up of GEC benign thyroid nodules in a 'reasonably busy' community practice setting for a time period of up to 6 years appears to be a viable option to surgery in many patients with indeterminate cytology on initial biopsy, which of course is the main selling point of the test when it was brought to market."

Based on average Medicare reimbursement for thyroid surgery in South-Central Pennsylvania, plus facility fees — and minus the cost of genetic testing — Dr Michael calculated that the potential savings to the medical system in his sample would be around $91,000, noting that periodic office visits and ultrasounds are the only remaining costs.

But Dr Lieb pointed out that questions remain about how long and how frequently the GEC-benign patients who don't go to surgery should be followed. And "are there certain people with a more concerning-looking nodule whom you advise to come back in 6 months? Are there patients who don't need another ultrasound for 3 years, or don't ever need another ultrasound again? I think a lot of the increased costs in thyroid nodules are patients who have a lot of ultrasounds who don't really need them."

Dr Michael added that the Afirma/GEC's false negative rate in clinical practice also still needs to be determined, since the numbers were too small in this study to be meaningful. In the future, larger numbers of GEC benign patients who undergo surgery for other reasons will be needed to answer that question, he noted.

In the meantime, he said, "In 2017 clinical judgment using all the historic and diagnostic data still trumps any single test.…I think we're still obligated intellectually to continue examining this issue and if we forget, I'm sure our friends at the various paying groups…will remind us."

Dr Michael is on the speaker's bureau for Veracyte and Genzyme. Dr Lieb has no relevant financial relationships.  

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American Association of Clinical Endocrinologists 2017 Annual Scientific & Clinical Congress. May 7, 2017; Austin, Texas. Abstract 1067.

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