The following is a summary of “Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis,” published in the June 2023 issue of Endocrinology & Metabolism by Nasr, et al.

The Afirma® Gene Sequencing Classifier (GSC) is used to risk stratify indeterminate thyroid nodule cytology (ITN). The previously conducted 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 independently published. For a study, researchers sought to compare the real-world performance of the GSC to the metrics reported in the validation study.

The analysis was conducted based on certain rules and assumptions: For inclusion in SN, SP, and NPV analyses, a study must have at least one patient with molecular benign results who underwent surgery. Molecular benign results without surgical histology and benign results with surgical histology are considered true negatives. Unoperated patients with suspicious results are either excluded from analysis (observed positive predictive value [oPPV] and observed specificity [oSP]) or assumed to be histology negatives, i.e., false positives, leading to conservative positive predictive value (cPPV) and conservative specificity (cSP). Noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered malignant.

In the real-world studies, the GSC demonstrated a sensitivity, oSP, oPPV, and NPV of 97%, 88%, 65%, and 99%, respectively. Conservative real-world performance showed cSP of 80% and cPPV of 49%, all significantly higher than the metrics reported in the validation study, except for sensitivity and cPPV. Additionally, there was a higher benign call rate (BCR) of 67% in the real-world studies compared to 54% in the validation study (P < 0.05).

The real-world data for the Afirma GSC indicates significantly better-observed specificity and positive predictive value than the validation study, leading to an increased yield of cancers in surgically resected GSC suspicious nodules. The higher BCR may contribute to a higher overall rate of clinical observation instead of surgery.

Source: academic.oup.com/jcem/article/108/6/1526/6873948