Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing

Abstract

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 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 (GEC) 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 nodules benign, 1 nodule noninvasive follicular thyroid neoplasm 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 5% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.

Longitudinal Assessment of Quality of Life Following Molecular Testing for Indeterminate Thyroid Nodules

“…Third, we do not have surveillance data for benign molecular test patients who may have experienced nodule progression that could have impacted QOL. However, based on our previous results from ultrasound surveillance over a median follow-up of 27 months, 84% of nodules remained stable in size and appearance, 28 therefore this variable is unlikely to significantly affect QOL outcomes observed in our study. Lastly, there was loss of patients during longititudinal follow-up, which may introduce nonresponse bias.…”

Comparison of Afirma GEC and GSC to Nodules Without Molecular Testing in Cytologically Indeterminate Thyroid Nodules

“…Another limitation of this study is the inability to formally characterize patients with benign molecular testing who did not undergo surgery for confirmation of benignity. Up to a 6% false-negative rate has been reported in those with benign molecular testing, discovered by changes on serial ultrasound assessment longitudinally [ 29 ]. However, this is a limitation of all retrospective indeterminate thyroid FNA molecular studies, given surgery is avoided in all those with benign molecular test results.…”

Differences in the management of thyroid nodules in children and adolescents as compared to adults

“…An adult group detailed their use of next-generation sequencing in these lesions, noting the results led to safe, nonoperative surveillance in >80% of lesions and a four-fold increased rate of malignancy in resected nodules [69 ▪ ]. Another institutional study looked at molecular testing in both Bethesda III and IV lesions, and showed successful 3–4 years surveillance of those with benign testing, with about a 5% false negative rate for molecular testing [70]. In pediatric patients with Bethesda category III cytology, molecular testing showing a gene fusion (e.g.…”