Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules

Abstract

Context Molecular testing has reduced the need for diagnostic hemithyroidectomy for indeterminate thyroid nodules. No studies have directly compared molecular testing techniques. Objective Compare the diagnostic performance of Afirma Gene Expression Classifier (GEC) with that of ThyroSeq v2 next-generation sequencing assay. Design Parallel randomized trial, monthly block randomization of patients with Bethesda III/IV cytology to GEC or ThyroSeq v2. Setting University of California, Los Angeles. Participants Patients who underwent thyroid biopsy (April 2016 to June 2017). Intervention Testing with GEC or ThyroSeq v2. Main Outcome Measure Molecular test performance. Results Of 1372 thyroid nodules, 176 (13%) had indeterminate cytology and 149 of 157 eligible indeterminate nodules (95%) were included in the study. Of nodules tested with GEC, 49% were suspicious, 43% were benign, and 9% were insufficient. Of nodules tested with ThyroSeq v2, 19% were mutation positive, 77% were mutation negative, and 4% were insufficient. The specificities of GEC and ThyroSeq v2 were 66% and 91%, respectively (P = 0.002); the positive predictive values of GEC and ThyroSeq v2 were 39% and 57%, respectively. Diagnostic hemithyroidectomy was avoided in 28 patients tested with GEC (39%) and 49 patients tested with ThyroSeq v2 (62%). Surveillance ultrasonography was available for 46 nodules (45 remained stable). Conclusions ThyroSeq v2 had higher specificity than Afirma GEC and allowed more patients to avoid surgery. Long-term surveillance is necessary to assess the false-negative rate of these particular molecular tests. Further studies are required for comparison with other available molecular diagnostics and for newer tests as they are developed.