Molecular genetic tests are increasingly used to determine the need for surgery in thyroid nodules with indeterminate fine-needle aspiration (FNA) cytopathology. However, the accuracy of these tests remains uncertain. This systematic review and meta-analysis analyze the diagnostic performance of molecular testing in pre-operative FNA biopsies from indeterminate thyroid nodules (ITN). We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The preoperative FNA cytopathology from patients over 14 years old, and the postoperative histopathology results were extracted. It was also essential to include true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) counts, along with genetic testing results. Sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) were calculated for each molecular panel using a random-effects bivariate model. Overall, 68 studies (2018–2024) were eligible discussing 7 different panels, from 16 countries. Multigene Point-of-care Test (MPTX v1) demonstrated the strongest ability to rule out malignancies (NLR 0.12; n = 4) and exhibited the highest diagnostic value (DOR 18; n = 4). ThyroSeq v2 Next-Generation Sequencing Test for Thyroid Cancer (ThyroSeq v2) followed with a DOR of 10 (n = 9). The PCR groups(n = 20) could not be merged due to significant methodological heterogeneity. This meta-analysis highlights the role of molecular testing in improving the diagnostic accuracy of indeterminate thyroid nodules, potentially reducing unnecessary surgeries. However, further standardization and validation are needed due to study heterogeneity.
Liao et al. (2025) studied this question.