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

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 3; pp. e428 - e435
• Main Authors: San Martin, Vicente T, Lawrence, Lima, Bena, James, Madhun, Nabil Z, Berber, Eren, Elsheikh, Tarik M, Nasr, Christian E
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.03.2020; Copyright Oxford University Press
• Subjects: Aged; Aged, 80 and over; Benign; Biomarkers - analysis; Biopsy, Fine-Needle; Case-Control Studies; Cytodiagnosis - methods; Cytology; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Follow-Up Studies; Gene expression; Gene Expression Profiling; Humans; Male; Middle Aged; Nodules; Prognosis; Retrospective Studies; Software; Statistical analysis; Surgery; Thyroid; Thyroid cancer; Thyroid gland; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - surgery; Thyroid Nodule - diagnosis; Thyroid Nodule - surgery; thyroid nodule; Genomic Sequencing Classifier; Afirma; Gene Expression Classifier; indeterminate cytology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz099

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.