The multigene classifier test ThyroSeq Version 3 (University of Pittsburg/CBLPath) shows high accuracy in diagnosing indeterminate thyroid nodules, allowing for more than 60% of patients with such nodules to avoid diagnostic surgery, according to the final results of a multicenter, double-blinded study.

"Our study showed ThyroSeq can help avoid surgery in the vast majority of patients with benign nodules where the initial biopsy returns an ambiguous result," senior author Yuri Nikiforov, MD, PhD, professor of pathology and director, Division of Molecular and Genomic Pathology, University of Pittsburgh School of Medicine, Pennsylvania, said in a press statement from his institution.

"With such a high proportion of preventable surgeries, this test should practically resolve the decades-long struggle and inefficiency of medical care for patients with indeterminate cytology thyroid nodules," he added. The research was previously described at the 2017 annual meeting of the American Thyroid Association. Final results were published online November 8 in JAMA Oncology.

All False Negatives Were Low-Risk Cancers

Although fine-needle aspiration (FNA) biopsy is highly effective in classifying most nodules as being either benign or malignant, approximately 20% of nodules remain indeterminate and require surgery to confirm a diagnosis.

Molecular testing of the nodules with genetic classifiers has emerged in the past decade and has improved the diagnostic accuracy of FNA. However, such tests have relatively low specificity and positive predictive value (PPV), provide limited clinical validation, or are limited in their capacity to provide specific molecular information, the researchers explain.

In the prospective evaluation of the ThyroSeq V3 genetic classifier, which is designed to detect up to 112 genes, a total of 286 nodules from 256 patients were subjected to blinded molecular analysis at 10 medical centers.

Of 257 indeterminate nodules that could be analyzed by ThyroSeq as well as by diagnostic surgery, 154 were classified as Bethesda category III, 93 as Bethesda IV, and 10 as Bethesda V.

For the primary outcome of accuracy in diagnosing Bethesda III and IV nodules, the ThyroSeq test showed high sensitivity, with a PPV of 94%, as well as high specificity, with a negative predictive value (NPV) of 82%. For 61% nodules, test results were negative.

Of the 28% of nodules that were malignant (24%) or noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP; 4%), the ThyroSeq test had an NPV of 97% and a PPV of 66%. The false negative rate was 3%, which is similar to that of FNA for benign nodules. All of the cancers that were incorrectly diagnosed as negative were low-risk tumors, the authors note.

"Although no test has perfect accuracy, it is reassuring that all false-negative cases in the study were low-stage and low-risk cancers by the American Thyroid Association criteria," the investigators noted.