EBUS-guided transbronchial mediastinal cryobiopsy for diagnosing non-metastatic lymphadenopathy: a randomized controlled trial

BACKGROUND: Non‐metastatic lymphadenopathy is challenging to diagnose. The comparative diagnostic performance of endobronchial ultrasound (EBUS)‐guided transbronchial mediastinal cryobiopsy (TBMC) vs. EBUS‐transbronchial needle aspiration (TBNA) remains debated. METHODS: This multicenter randomized trial was conducted in three hospitals. Patients with at least one mediastinal and/or hilar lesion of ≥1 cm in the short axis who required diagnostic bronchoscopy were included. The patients were randomized in a 1:1 ratio to receive either EBUS‐TBNA followed by EBUS‐TBMC (EBUS‐TBNA‐first group) or EBUS‐TBMC followed by EBUS‐TBNA (EBUS‐TBMC‐first group). The primary outcome was the diagnostic yields of EBUS‐TBMC and EBUS‐TBNA. FINDINGS: The overall diagnostic yield of EBUS‐TBMC for non‐metastatic lymphadenopathy was significantly higher than that of EBUS‐TBNA for specific benign etiologies and lymphomas (97.1% vs. 79.9%, p < 0.001). In the subgroup analysis, EBUS‐TBMC showed a higher sensitivity for sarcoidosis than EBUS‐TBNA (98.0% vs. 82.7%, p < 0.001). All patients experienced grade 1 airway bleeding. CONCLUSIONS: EBUS‐TBMC demonstrated a higher diagnostic yield than EBUS‐TBNA for non‐metastatic lymphadenopathy in a cohort almost exclusively composed of sarcoidosis cases, with a good safety profile. EBUS‐TBMC is a potential first‐line diagnostic tool for non‐metastatic lymphadenopathy. FUNDING: This work was financially supported by the Noncommunicable Chronic Diseases‐National Science and Technology Major Project (2024ZD0528900 and 2024ZD0528902 to G.H.).