Abstract / Summary
Molecular testing (MT) aids in the management of indeterminate thyroid nodules; however, regional differences remain unexamined. This meta-analysis compares MT's clinical impact between Western and Asian cohorts. This study hypothesized that regional disparities in malignancy prevalence, molecular platforms, and practice patterns would yield divergent clinical applications of MT. A systematic review up to April 2025 identified studies reporting the surgical management and histopathological outcomes of indeterminate nodules in Asian and Western cohorts, stratified by use of MT versus no MT. Pooled proportions were calculated via random-effects models. Of 127 included studies (100 Western; 27 Asian), MT was performed in 96 Western and 21 Asian studies. Western studies predominantly used commercial panels, whereas Asian studies favored smaller, mutation-specific assays. Without MT, resection rates were 66.8% (95% CI, 55.1%-76.7%) in Western studies versus 53.9% (95% CI, 43.5%-64.0%) in Asian studies (p = .11). With MT, rates fell to 42.5% versus 37.4% (p = .275), respectively. Risk of malignancy (ROM) was significantly higher in Asian cohorts, both without MT (48.0% vs. 29.5%; p = .005) and with MT (62.7% vs. 37.1%; p < .001), which persisted after exclusion of follicular thyroid neoplasm with papillary-like nuclear features. In Western studies, second-generation platforms achieved lower resection rates (36.1% vs. 48.3%; p = .001) but higher ROM (42.8% vs. 34.4%; p = .005) than first-generation tests. MT reduces surgical interventions across both regions by serving divergent roles. In the West, MT functions as a rule-out tool to avoid surgery via comprehensive panels. In Asia, where baseline malignancy is higher and practice is relatively conservative, MT provides confirmatory risk stratification via focused mutation panels. Regionally tailored guidelines are warranted.