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.

Contemporary Thyroid Nodule Evaluation and Management

“…Compared with the previous version, the new test correctly classifies more indeterminate nodules as benign and displays improved specificity (68.3%) and positive predictive value (47.1%), with a sensitivity of 91.1% and a negative predictive value of 96.1% ( 67 ). It is expected to further reduce the frequency of diagnostic surgery, based on the results of independent studies ( 72-74 ). In short, the ThyroSeq and Afirma assays currently have positive and negative predictive values that make them suitable for use in both rule-in and rule-out testing.…”

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis

“…This implies an effort to develop US RSSs able to intercept FTC and MTC cases. On the other hand, a great effort is underway in validating molecular tests to improve cytological diagnosis [42][43][44][45]. In the meantime, international guidelines have sped up this process by promoting the potential of molecular tests in clinical practice [12,41].…”

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

“…For the Afirma-GSC, San Martin and colleagues found that the second generation test has a higher specificity (94 vs. 60%) while retaining similar negative predictive value (96.3 vs. 98.6%) compared to the GEC. This resulted in improved performance within specimens with Hürthle cell cytology, improved overall benign call rate of 68% ( vs. 41%) and a decrease in surgery rate from 48 to 35% for the population as a whole ( 36 ). Wei and colleagues have documented that the benign call rate for GSC is considerably higher than GEC (66.7 vs. 45.4%), and Endo and colleagues have reported a benign call rate of 88.8 vs. 25.7% for GSC vs. GEC for samples with Hürthle cells ( 37 , 38 ).…”

“…Prospective studies assessing the impact of these tests on the rate and appropriateness of surgical intervention are lacking, and most of the information is gleaned from retrospective data only. Moreover, many of the series suggesting that implementation of molecular testing leads to reduction in number of surgeries are correlative in nature, i.e., they show that fewer surgeries were done during period of molecular testing use compared to historical time period when testing was not used, but they do not directly show a causal effect at the individual patient/nodule level ( 36 , 39 , 42 ).…”