University of Cincinnati Researchers Study Novel Diagnostic Test for Suspicious Thyroid Nodules
High negative predictive value can prevent unnecessary diagnostic biopsy surgeries in 50% of patients
Thyroid surgery has been traditionally used to diagnose cancer in the presence of cytologically indeterminate thyroid nodules. However, a new gene mutation test may be able to replace surgery for many patients. The feasibility of analyzing DNA and RNA from thyroid nodules of patients undergoing fine-needle biopsy was initiated at the University of Cincinnati Medical Center, says David L. Steward, MD, Professor of Otolaryngology – Head and Neck Surgery. The addition of DNA and RNA mutation testing proved to be more accurate than fine needle biopsy for cytology alone, but gaps in diagnostic ability to exclude cancer still existed.1 In partnership with industry, a gene-expression classifier was developed to exclude malignancy for indeterminate nodules.1 When its performance was assessed, results published in the New England Journal of Medicine demonstrated that the gene-expression classifier correctly identified 92% of the indeterminate nodules as benign, and 94-95% of the atypical or possible follicular neoplasms as benign.2
Despite having only been reported on two years ago, the diagnostic test is already part of the National Comprehensive Cancer Network (NCCN) guidelines, and will be likely included in the upcoming revision of the American Thyroid Association Thyroid Cancer guidelines.
The test has the potential to allow patients to avoid diagnostic surgery when their fine-needle biopsy cytology results are indeterminate for possible thyroid cancer, with an estimated risk in the 30% range for those nodules deemed cytologically atypical or possible follicular neoplasm, Steward explains. Clinicians must weigh each patient’s clinical risk factors along with the sonographic risk assessment of the nodule and determine whether to perform this new test or proceed with diagnostic surgery. This is a “rule-out” cancer test with a high negative predictive value.
Another test with high positive predictive value may be used to determine if the nodule is cancerous but is less able to exclude cancer and thus avoid surgery for the patient. Says Steward, “We as clinicians want it both ways. We want a test that says ‘yes, it’s cancer’ or ‘no, it’s not’ every time, but it turns out that you can’t have it both ways. However, a next-generation test is currently undergoing multi-institutional study, including at the University of Cincinnati, that will hopefully be able to improve both sensitivity and specificity so that cancer can be ruled out or in with one test.”
“This would allow us as surgeons to avoid unnecessary surgery on those patients who have benign thyroid nodules, and optimize oncologic surgery for those patients with malignancies.”
References:
1. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules.
Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN. J Clin Endocrinol Metab. 2009 Jun;94(6):2092-8. doi: 10.1210/jc.2009-0247. Epub 2009 Mar 24. PMID: 19318445
2.Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J et al. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. N Engl J Med 2012;367:705-15.
David L. Steward, MD
Professor of Otolaryngology
University of Cincinnati Medical Center
Director, Division of Thyroid/Parathyroid Disorders, UC Department Otolaryngology-
Head and Neck Surgery
Director, Clinical Research Program and Co-Director, Resident Research Program,
UC Department Otolaryngology-Head and Neck Surgery,
Medical School: University of Cincinnati College of Medicine
(513) 558-4199
Stewardd@ucmail.uc.edu