Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Abstract

BackgroundMolecular tests are being used increasingly as an auxiliary diagnostic tool so as to avoid a diagnostic surgery approach for cytologically indeterminate thyroid nodules (ITNs). Previous test versions, Thyroseq v2 and Afirma Gene Expression Classifier (GEC), have proven shortcomings in malignancy detection performance.ObjectiveThis study aimed to evaluate the diagnostic performance of the established Thyroseq v3, Afirma Gene Sequencing Classifier (GSC), and microRNA-based assays versus prior iterations in ITNs, in light of “rule-in” and “rule-out” concepts. It further analyzed the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification and Bethesda cytological subtypes on the performance of molecular tests.MethodsPubmed, Scopus, and Web of Science were the databases used for the present research, a process that lasted until September 2020. A random-effects bivariate model was used to estimate the summary sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and area under the curve (AUC) for each panel. The conducted sensitivity analyses addressed different Bethesda categories and NIFTP thresholds.ResultsA total of 40 eligible studies were included with 7,831 ITNs from 7,565 patients. Thyroseq v3 showed the best overall performance (AUC 0.95; 95% confidence interval: 0.93–0.97), followed by Afirma GSC (AUC 0.90; 0.87–0.92) and Thyroseq v2 (AUC 0.88; 0.85–0.90). In terms of “rule-out” abilities Thyroseq v3 (NLR 0.02; 95%CI: 0.0–2.69) surpassed Afirma GEC (NLR 0.18; 95%CI: 0.10–0.33). Thyroseq v2 (PLR 3.5; 95%CI: 2.2–5.5) and Thyroseq v3 (PLR 2.8; 95%CI: 1.2–6.3) achieved superior “rule-in” properties compared to Afirma GSC (PLR 1.9; 95%CI: 1.3–2.8). Evidence for Thyroseq v3 seems to have higher quality, notwithstanding the paucity of studies. Both Afirma GEC and Thyroseq v2 performance have been affected by NIFTP reclassification. ThyGenNEXT/ThyraMIR and RosettaGX show prominent preliminary results.ConclusionThe newly emerged tests, Thyroseq v3 and Afirma GSC, designed for a “rule-in” purpose, have been proved to outperform in abilities to rule out malignancy, thus surpassing previous tests no longer available, Thyroseq 2 and Afirma GEC. However, Thyroseq v2 still ranks as the best rule-in molecular test.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier CRD42020212531.

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada

“…Advances in thyroid tumor molecular characterization have resulted in the development of multiple molecular commercial tests to supplement cytology and US and improve risk stratification and management decision-making for thyroid nodules [ 51 ] ( Table 1 ). The molecular tests are categorized as either a rule in or rule out tests depending on their capacity to either confirm or exclude malignancy [ 51 ]. To rule out malignancy, a test needs to have a high sensitivity and a high negative predictive value (NPV).…”

Down-regulation of miR-7-5p and miR-548ar-5p predicts malignancy in indeterminate thyroid nodules negative for BRAF and RAS mutations

“…A recent meta-analysis has investigated the diagnostic performance of the main commercial tests dedicated to thyroid cytology, including ThyroSeq v3 and Afirma Genome Sequencing Classifier (GSC) [ 19 ]. These two tests were confirmed as having a good NPV, higher than 90%.…”

The Autoantibodies against Tumor-Associated Antigens as Potential Blood-Based Biomarkers in Thyroid Neoplasia: Rationales, Opportunities and Challenges

“…The state-of-the-art molecular testing (reviewed in [ 87 ]), in particular, the ThyroSeq ® v3 platform [ 88 , 89 , 90 ], proved to be very useful in TBSRTC DC3 and TBSRTC DC4 nodules. With the unprecedentedly high DSn (pooled value 99% [95% CI 90–100%] reported in a recent meta-analysis [ 91 ]), ThyroSeq ® v3 is capable of accurately ruling out malignancy in approximately three-quarters of TBSRTC DC3 and TBSRTC DC4 nodules [ 89 ]. However, the most frequent genetic alterations characteristic of FPT (e.g., HRAS , KRAS , and NRAS mutations) demonstrate comparable prevalence in benign, borderline, and malignant FPT [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ], resulting in only moderate DSp of this test (pooled value 64% [95% CI 32–87%] [ 91 ]), with other diagnostic tests available on the market demonstrating even lower DSp values (Afirma Gene Expression Classifier (GEC) [ 99 ]: 19% [95% CI 15–24%]; Afirma Gene Sequencing Classifier (GSC) [ 100 , 101 ]: 51% [95% CI 33–69%] [ 91 ]).…”