Comparing the diagnostic accuracy of Afirma GSC to ThyroSeq V3 in cytologically indeterminate thyroid nodules

Objective To compare the diagnostic test accuracy of Afirma GSC and ThyroSeq v3 in cytologically indeterminate thyroid nodules. Methods PubMed, Embase, Cochrane Library, Medline, and the Web of Science were searched from the date of inception to May 9, 2025. Two independent reviewers screened articles for eligibility. Studies assessing Afirma gene sequencing classifier (GSC) or ThyroSeq v3 for indeterminate thyroid nodules were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines were followed. Statistical analysis was performed using R. Results A total of 26 studies met the eligibility criteria. For surgically confirmed Afirma GSC results, the sensitivity, specificity, and negative predictive value (NPV) were 94, 42, and 96%, respectively. For unoperated negative cases, the values were 96, 86, and 99%. For ThyroSeq v3, the sensitivity, specificity, and NPV for surgically confirmed cases were 96, 40, and 93%, respectively, and for unoperated negative cases, they were 97, 83, and 99%. Conclusion Both molecular tests demonstrate high NPV but low specificity; neither is clearly superior. Future research should prioritise randomised controlled trials, long-term follow-up of unoperated nodules, and direct comparisons of molecular tests.