Multigene Classifier Test for Thyroid Nodules With Indeterminate Cytology


Key Points

  • The test had a negative predictive value of 97% and positive predictive value of 66%.
  • Based on study findings, use of the test could allow up to 61% of patients with indeterminate cytology to avoid diagnostic surgery.

In a study reported in JAMA Oncology, Steward et al found that the use of a multigene genomic classifier test (ThyroSeq v3) could reduce the need for diagnostic surgery in a substantial proportion of patients with thyroid nodules with indeterminate cytology.

The blinded prospective cohort study recruited 782 patients with 1,013 thyroid nodules who were evaluated at 9 sites in the United States and 1 in Singapore between January 2015 and December 2016. Of these, 286 nodules in 256 patients were cytologically indeterminate, with fine-needle aspiration samples from these nodules being analyzed with the genomic classifier test. The primary outcome measure was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology.

Genomic Classifier Test Accuracy

Based on central pathology review, of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) were malignant, and 11 (4%) were noninvasive follicular thyroid neoplasms with papillary-like nuclei. Genomic classifier molecular analysis was successful for 257 nodules (90%), including 154 with Bethesda III, 93 Bethesda IV, and 10 Bethesda V cytology; of these, 61% of nodules were classified as negative and 39% as positive.

For Bethesda III and IV nodules combined, with a prevalence of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclei of 28%, the genomic classifier test had 94% sensitivity and 82% specificity, negative predictive value of 97%, and positive predictive value of 66%. The 3% of false-negative cases were all low-risk tumors. Among the nodules with positive genomic classifier test findings, the specific groups of genetic alterations had cancer probabilities ranging from 59% to 100%.

The investigators concluded: “In this prospective, blinded, multicenter study, the multigene genomic classifier test demonstrated a high sensitivity/[negative predictive value] and reasonably high specificity/[positive predictive value], which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from [fine-needle aspiration] may help inform individualized treatment of patients with a positive test result.”

The study was supported by a Head and Neck Cancer SPORE grant to University of Pittsburgh and a Thyroid Cancer SPORE grant to The Ohio State University.

Yuri E. Nikiforov, MD, PhD, of the Department of Pathology, University of Pittsburgh, is the corresponding author for the JAMA Oncology article.

Disclosure: See study authors’ full disclosures at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.