Real-world Comparison of Afirma GEC and GSC for the Assessment of Cytologically Indeterminate Thyroid Nodules

Abstract

Context

Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC.

Objective

The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules.

Design, Settings, and Participants

Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance.

Results

The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant.

Conclusions

GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.