A Stepwise Diagnostic Strategy Combining a Simplified US-Based Node-RADS with Postvascular Phase Perfluorobutane-CEUS for Indeterminate Cervical Lymph Nodes: A Dual-Center Retrospective Study.

OBJECTIVE: To develop a conventional ultrasound (US)-based Node-reporting and data systems (US-Node-RADS) for cervical lymph nodes (CLNs) and to evaluate whether the subsequent application of postvascular phase perfluorobutane-contrast-enhanced ultrasound (CEUS) can reclassify its indeterminate (Node-RADS 3) category and reduce unnecessary biopsies. METHODS: In this dual-center retrospective study, data were analyzed from patients whose imaging had been prospectively acquired under a standardized protocol. A 5-point US-Node-RADS was developed in a training set (n = 356) and validated internally (n = 152) and externally (n = 45). For nodes classified as indeterminate Node-RADS 3, PVP-CEUS was applied: iso-/hyperenhancement prompted downgrading to Node-RADS 2 (follow-up), while no-/hypoenhancement prompted upgrading to Node-RADS 4 (biopsy). Histopathology and follow-up served as the reference standard. Diagnostic performance metrics were statistically evaluated. RESULTS: The US-based Node-RADS showed moderate diagnostic performance (AUC 0.78 in training) but left a substantial proportion (40.2%) of nodes in the indeterminate Node-RADS 3 category. Applying PVP-CEUS to these nodes successfully reclassified them, safely avoiding 14.7% to 40.0% of unnecessary biopsies across the cohorts. This was achieved while maintaining high malignancy identification rates, which increased to 79.3%-100% after reclassification, exceeding the baseline malignancy rates for Node-RADS 3 (training set: 67.8%; internal validation: 69.0%; external validation: 60.0%). CONCLUSION: Applying PVP-CEUS to Node-RADS 3 nodes effectively resolves diagnostic ambiguity for indeterminate CLNs. This two-step strategy significantly reduces unnecessary biopsy procedures while preserving high sensitivity for malignancy identification, can serve as a potential standardized and actionable pathway to aid preoperative decision-making in appropriately selected patients.