Real World Performance of The Afirma Genomic Sequencing Classifier (GSC) - A Meta-analysis

Context: The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real world (RW) post-validation studies have been published. Objective: This study\u27s objective is to compare the RW GSC performance to the VS metrics. Methods: Rules and assumptions applying to this analysis include: 1. At least one patient with molecular benign results must have surgery for that study to be included in SN, SP and NPV analyses. 2. Molecular benign results without surgical histology are considered true negatives (TN) (as are the molecular benign results with benign surgical histology) 3. Unoperated patients with suspicious results are either excluded from the analysis (observed PPV (oPPV) and observed SP (oSP)) or assumed as histology negatives (false positives - conservative PPV (cPPV) and conservative SP (cSP)) 4. NIFTP is considered malignant. Results: In RW studies, the GSC demonstrates a SN, oSP, oPPV and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS save for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (p \u3c 0.05). Conclusion: RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance compared to the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery