Recent Study Shows That, Yes, We Can Leave More Thyroids Intact


Lindsay Lipe, MS, CGC
Joshua Klopper, MD

July 27, 2022

For many years, thyroid nodules with indeterminate cytology have been a conundrum for physicians. Historically, most of these nodules were managed with diagnostic surgery (often a lobectomy), which frequently turned out to be unnecessary.1-3 Fortunately, we’ve made major strides in the management of patients with indeterminate nodules, including the advent of advanced genomic testing.3-5

Current American Thyroid Association guidelines include molecular testing as a recommended option to achieve definitive diagnosis for nodules classified as indeterminate following fine needle aspiration (FNA) biopsy.6  A recent publication in the Journal of the Endocrine Society adds to the body of evidence supporting molecular testing among these patients, specifically exploring how use of the Afirma Genomic Sequencing Classifier (GSC) impacted the surgical rate among patients with indeterminate thyroid nodule cytology in a large practice.7

The Afirma GSC is a commercially available molecular test designed to reduce unnecessary diagnostic thyroid surgeries. Multiple, previous studies have demonstrated the validity and clinical utility of this genomic test. 3, 4, 8

In the recent study, Dr. Preethi Polavarapu and colleagues at the University of Nebraska Medical Center assessed patients with Bethesda III (AUS/FLUS) and Bethesda IV (SFN/FN) nodules over a seven-year period from January 2013 to December 2019, comparing surgical and malignancy rates among those without molecular testing to those tested with the Afirma GSC and the predecessor Afirma Genomic Expression Classifier.

A total of 468 indeterminate nodules were included in the study and analysis; 273 (58%) had no molecular testing, 124 were tested with the Afirma GSC (26%), and 71 were tested with the Afirma GEC (16%). Researchers found that surgical rate decreased by 28% among patients who whose nodules were tested with the genomic test vs. those who received no molecular testing (40% vs. 68%).

There was an even more striking difference in surgical rates among patients with Bethesda IV nodules: 33% of those tested with the Afirma GSC underwent surgery compared to 79% in the group without molecular testing – a 46% difference. As expected, malignancy rates also differed by group, with patients tested with the Afirma GSC almost twice as likely to have cancer upon surgery as those who were not tested.

A final important finding was that among those patients who did not undergo molecular testing, the primary reason given was that it was not offered by the treating physician (56%).

This study provides compelling additional evidence that genomic testing can help us resolve a long-standing challenging in thyroid nodule diagnosis, improving decision-making and outcomes for patients with indeterminate FNA cytology.


1 Wang CC, et. al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011 Mar;21(3):243-51. Epub 2010 Dec 29.

2 Cibas ES, et. al. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Ann Intern Med. 2013 Sep 3;159(5):325-32.

3 Patel KN, et. al. Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules. JAMA Surg. 2018 Sep 1;153(9):817-824.

4 Endo M, Nabhan F, Porter K, Roll K, Shirley LA, Azaryan I, Tonkovich D, Perlick J, Ryan LE, Khawaja R, Meng S, Phay JE, Ringel MD, Sipos JA. Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules. Thyroid. 2019 Aug;29(8):1115-1124.

5 Endo M, et. al. Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules. Thyroid. 2019 Aug;29(8):1115-1124.

6 Haugen BR, et. al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016, 26 (1), 1-133

7 Polavarapu P, et. al. Comparison of Afirma GEC and GSC to Nodules Without Molecular Testing in Cytologically Indeterminate Thyroid Nodules. J Endocr Soc. 2021 Oct 7;5(11).

8 Gortakowksi M, et al. Single institution experience with Afirma and Thyroseq testing in indeterminate thyroid nodules