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Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing
Catherine Y Zhu1, Ines Donangelo2, Deepashree Gupta2
1Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Context:
Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited.
Objective:
Determine the delayed rate of surgical resection in indeterminate nodules with benign/negative molecular testing and the risk of false-negative molecular test results.
Design:
Prospective follow-up of the Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules randomized controlled trial comparing the diagnostic test performance of Afirma Gene Expression Classifier and ThyroSeq v2.
Setting:
University of California, Los Angeles.
Participants:
Patients who underwent thyroid biopsy with indeterminate (Bethesda III/IV) cytology (April 2016 to July 2017).
Intervention:
Ultrasound surveillance.
Main Outcome Measure:
False-negative rate of molecular testing.
Results:
Of 95 indeterminate nodules with negative/benign molecular test results, 12 nodules underwent immediate resection (11 benign nodules, 1 noninvasive follicular thyroid neoplasm nodule with papillary-like nuclear features). Nonoperative management was pursued for 83 (87.4%) nodules. The median surveillance was 26.7 months. Ten nodules were resected during surveillance and malignancy was identified in 4 nodules (overall false-negative rate of 5.8%). In the 4 malignant nodules that underwent delayed operation, surgery was prompted by sonographic changes during surveillance.
Conclusions:
The majority of indeterminate nodules with negative molecular testing have a stable clinical course over 3 years of follow-up, but our finding of a 6% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.

