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Molecular testing may mitigate mystery of indeterminate thyroid nodules
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Recently, Argentine President Cristina Fernandez underwent a total thyroidectomy — one that physicians now know was unnecessary — to treat what was thought to be thyroid cancer. Unfortunately, many physicians are familiar with this scenario.
“This is a well-known event in thyroid fine-needle aspiration (FNA) of nodules,” R. Michael Tuttle, MD, professor of medicine and attending physician at Memorial Sloan-Kettering Cancer Center, told Endocrine Today, noting that most large studies show that FNA has a false-positive rate of 1% to 2%.
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Additionally, according to Jeffrey R. Garber, MD, president-elect of the American College of Endocrinology and an Endocrine Today Editorial Board member, the possibility for misclassification of a nodule can be “either unusual or common.”
“If the cytopathologist calls [the nodule] papillary thyroid cancer, in good hands, the false-positive rates are generally around 1%,” Garber said in an interview. “If the cytopathologist deems it suspicious for papillary cancer, it turns out to be cancer somewhere between 50% and 70% of the time, depending on the institution. On the other hand, if it is called a follicular neoplasm or indeterminate, including follicular variant of papillary thyroid cancer, it turns out to be malignant as infrequently as 10% and generally no more than 25% of the time.”
If the odds that the nodule is cancer exceed 50%, bilateral surgery is recommended, Garber said, and if the odds are significantly lower, a discussion about more limited surgery and the possible need for a second “completion” thyroidectomy may be necessary.
New tests, new possibilities
Results from an article published in 2010 in the Journal of Clinical Endocrinology & Metabolism, however, showed that approximately 80% of patients with indeterminate cytology results undergo partial or complete thyroidectomy, raising the question of whether more accurate diagnoses could help prevent unnecessary procedures.
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In the study detailed in the article, researchers developed a molecular test designed to distinguish benign and malignant thyroid nodules using fine-needle aspirates. The test, now available as the Afirma Gene Expression Classifier (Veracyte), is a trained classifier that uses genes known to be present in thyroid cancer cells to diagnose nodules. Results from the study indicated that the gene expression test had a negative predictive value of 96% and a specificity of 84%, suggesting clinical utility in the management of patients considering surgery.
Data from a second study presented at the International Thyroid Congress in 2010 yielded similar results. When compared with expert histopathology over-reads, researchers also found that the molecular classifier had a sensitivity of 95%, specificity of 63% and negative predictive value of 96% for patients with indeterminate FNA cytology. Further, results suggested that, with the test, 63% of patients with indeterminate cytopathology could have safely avoided surgery.
Cutting costs
Besides increasing diagnostic accuracy, recent data from a study, also published in the Journal of Clinical Endocrinology & Metabolism, showed that the gene expression classifier is cost-effective. According to the data, use of the molecular test decreased the number of surgeries for benign nodules by 74%, with no increase in the amount of untreated cancers. During 5 years, mean discounted cost estimates were $12,172 for current practice and $10,719 with the molecular test. Further, the savings to overall direct medical costs were more than $600 million.
In January, Veracyte announced that Palmetto GBA, a national contractor that administers Medicare benefits, established coverage for the Afirma Gene Expression Classifier. The decision means the genomic test is now available to 30 million Medicare patients worldwide, according to a press release.
“This decision will help Medicare patients with inconclusive FNA results access our Afirma Gene Expression Classifier, enabling them to potentially avoid surgery, while also saving money for the Medicare program,” Bonnie Anderson, co-founder and CEO of Veracyte, said in the release.
Current practice
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At present, diagnosis of thyroid nodules still remains fairly accurate, according to Endocrine Today Editorial Board member Stephanie L. Lee, MD, PhD, associate chief of the section of endocrinology, diabetes and nutrition, and associate professor of medicine at Boston Medical Center. She said, for example, that results from a 2009 study published in CA: A Cancer Journal for Clinicians showed that the Bethesda System for Reporting Thyroid Cytopathology confirmed FNA biopsies categorized as malignant 100% of the time. For suspicious nodules, however, confirmation of malignancy was 87%.
“It is very unusual that a FNA positive for thyroid cancer is not a cancer after thyroidectomy, but it can occasionally occur with a ‘suspicious of malignancy’ FNA biopsy,” Lee said.
Tuttle said it is important to keep this information in mind.
“For endocrinologists, it is worth remembering that FNA results are never 100% accurate, so it is important to tell patients that there is a very small chance that even if the FNA is interpreted as showing papillary thyroid cancer, the final histology after surgical removal may show a benign nodule,” he said. – by Melissa Foster
For more information:
- Chudova D. J Clin Endocrinol Metab. 2010;95:5296-5304.
- Haugen BR. LB137. Presented at: the 14th International Thyroid Congress; Sept. 11-16, 2010; Paris.
- Layfield LJ. CA Cancer J Clin. 2009;59:99-110.
- Li H. J Clin Endocrinol Metab. 2011;96:e1719-e1726.
Disclosure: Dr. Garber reports no relevant financial disclosures. Dr. Lee reports no relevant financial disclosures. Dr. Tuttle is a paid consultant for the Genzyme Corporation.