What is the key question?

• What is the safety profile and added value of the combined use of transbronchial mediastinal cryobiopsy and standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of mediastinal diseases?

What is the bottom line?

• This is an open-label, randomised trial at three hospital sites in Europe and Asia where participants were randomly assigned (1:1) to the combined use of EBUS-TBNA and transbronchial mediastinal cryobiopsy (combined group, n=136) or EBUS-TBNA alone (control group, n=135).
• The coprimary outcomes were differences in procedure-related complications and diagnostic yield (defined as the proportion of participants for whom mediastinal biopsy led to a definitive diagnosis). A fully paired, intraindividual diagnostic analysis in participants who had both needle aspiration and mediastinal cryobiopsy was conducted, in addition to interindividual comparisons.
• The addition of cryobiopsy to standard sampling was found to significantly increase the overall diagnostic yield for mediastinal lesions, as shown by both interindividual (p=0·0039) and intraindividual (p=0·0026) analyses.
• In subgroup analyses in the intraindividual population, diagnostic yields were similar for mediastinal metastasis (p=1·00), whereas the combined approach was more sensitive than standard needle aspiration in benign disorders (p=0·0009).
• The combined approach also resulted in an improved suitability of tissue samples for molecular and immunological analyses of non-small-cell lung cancer.
• The incidence of adverse events related to the biopsy procedure did not differ between trial groups, as grade 3--4 airway bleeding occurred in three (2%) patients in the combined group and two (1%) in the control group (p=1·00). There were no severe complications causing death or disability.

Why read on?

• The addition of mediastinal cryobiopsy to standard EBUS-TBNA may represent a valid first-line diagnostic tool for mediastinal diseases.