Gang Hou, Mingming Deng, Ziwen Zheng
Background: The best endobronchial ultrasound (EBUS)-guided approach for diagnosing mediastinal and/or hilar lymphadenopathy (MHL) among transbronchial needle aspiration (EBUS-TBNA), transbronchial mediastinal cryobiopsy (EBUS-TBMC), and transbronchial forceps biopsy (EBUS-TBFB) remains unclear.
Methods: This open-label, multicenter, parallel randomized controlled trial involved 11 centers in China. Adults with MHL needing tissue diagnosis were randomized to EBUS-TBNA, EBUS-TBMC, or EBUS-TBFB in a 1:1:1 ratio. The primary endpoint was diagnostic yield, with secondary outcomes including diagnostic sensitivity and safety assessed by complication and bleeding rates. The trial is registered at ClinicalTrials.gov (NCT06262620).
Results: From March 5, 2024, to November 25, 2025, 972 participants were randomized, all successfully undergoing their assigned biopsy. EBUS-TBMC had a higher diagnostic yield than EBUS-TBNA (86.1% vs 72.8%, p<0.001) and EBUS-TBFB (86.1% vs 77.2%, p=0.003). EBUS-TBFB did not significantly outperform EBUS-TBNA (77.2% vs 72.8%, p=0.20). EBUS-TBMC showed the highest sensitivity for diagnosing malignant (89.0%) and benign (93.0%) diseases compared to EBUS-TBNA and EBUS-TBFB. Grade 2 bleeding rates were 11.4%, 15.7%, and 12.4% in EBUS-TBNA, EBUS-TBMC, and EBUS-TBFB, respectively. No deaths were reported.
Conclusions: EBUS-TBMC is recommended as the primary diagnostic method for MHL in high-volume centers with cryobiopsy capabilities due to its superior diagnostic yield and safety.