Cryobiopsy versus conventional bronchoscopic sampling for peripheral pulmonary lesions (Cryo-RCT): an open-label, parallel-group, randomised trial.

Summary

In this six-centre randomized trial of 627 patients, stand-alone cryobiopsy produced a higher histology-based diagnostic yield than conventional bronchoscopic sampling. Yield was 83% versus 75% in the overall cohort and 77% versus 65% when the probe was adjacent to or eccentric from the lesion. Moderate bleeding was more common with cryobiopsy, while severe bleeding and serious adverse events remained uncommon.

Key Findings

• Among lesions with adjacent-to or eccentric probe positioning, diagnostic yield was 77% with cryobiopsy versus 65% with conventional sampling; estimated difference 12.4 percentage points, p=0.0060.
• In the overall randomized cohort, diagnostic yield was 83% with cryobiopsy versus 75% with conventional sampling; estimated difference 8.9 percentage points, p=0.0023.
• Moderate bleeding occurred in 38% versus 19% and pneumothorax in 2% versus less than 1% with cryobiopsy versus conventional sampling, respectively.

Clinical Implications

Cryobiopsy can be considered as a tissue-acquisition strategy for peripheral pulmonary lesions, particularly when radial endobronchial ultrasound shows an adjacent-to or eccentric probe-lesion relationship. Programs should ensure expertise in bleeding control and pneumothorax management because these complications were more frequent than with conventional sampling.

Limitations

• The trial was open-label, and procedural expertise may not be generalizable to all bronchoscopists or institutions.
• Cryobiopsy caused more moderate bleeding and pneumothorax, and the study does not establish the optimal number or size of cryobiopsy specimens.

Future Directions

Future studies should identify lesion- and operator-specific criteria for selecting cryobiopsy, compare different cryoprobe sizes and sampling protocols, and evaluate effects on molecular testing, repeat procedures, cost, and patient-centred outcomes.