CRYOBIOPSY improves the diagnostic yield of bronchoscopy for small peripheral lung lesions, according to an international randomised trial.
The Cryo-RCT study found that cryobiopsy provided a definitive histological diagnosis more often than conventional sampling, with particular benefit when the ultrasound probe was positioned adjacent to, or eccentrically relative to, the lesion.
Researchers conducted the open-label trial across six centres in Japan, Malaysia, South Korea, and Taiwan. Between November 2022 and March 2025, 660 patients were enrolled, and 627 were randomly assigned to cryobiopsy or conventional sampling.
Eligible participants were adults with peripheral pulmonary lesions measuring no more than 30 mm that could be visualised using radial endobronchial ultrasound. Randomisation took place after lesion visualisation, allowing the trial to compare the diagnostic contribution of the sampling techniques.
Cryobiopsy uses a cooled probe to freeze and retrieve tissue. The technique can obtain larger specimens with less damage than conventional sampling, potentially supporting both histological diagnosis and molecular testing.
Bronchoscopists using cryobiopsy aimed to obtain one to three specimens with single-use probes. Conventional sampling involved forceps, aspiration needles, or both, with at least five specimens collected where feasible.
In the overall analysis, histology-based diagnostic yield was 83% with cryobiopsy, compared with 75% using conventional sampling.
Among patients with an adjacent-to or eccentric probe-lesion relationship, diagnostic yield reached 77% with cryobiopsy versus 65% with conventional sampling. The estimated difference was 12.4 percentage points (95% CI: 2.8–22.0).
These results indicate that cryobiopsy may be particularly useful where the probe’s position relative to the lesion makes conventional tissue acquisition more difficult.
Moderate bleeding occurred in 38% of patients receiving cryobiopsy, compared with 19% receiving conventional sampling. Severe bleeding was uncommon, occurring in two and three patients, respectively.
Pneumothorax occurred in six cryobiopsy patients and one conventional sampling patient. Five patients in the cryobiopsy group required chest-tube drainage, compared with none in the conventional group. Serious adverse events were infrequent in both groups.
The findings support cryobiopsy as a valuable tissue-acquisition option for peripheral pulmonary lesions visualised using radial endobronchial ultrasound.
However, improved diagnostic yield must be weighed against the greater frequency of moderate bleeding and pneumothorax. Implementation requires appropriate procedural expertise, bleeding-control measures, and facilities to manage complications.
The trial provides evidence to inform technique selection, while reinforcing the importance of assessing diagnostic benefit and procedural risk together.
Matsumoto Y et al. Cryobiopsy versus conventional bronchoscopic sampling for peripheral pulmonary lesions (Cryo-RCT): an open-label, parallel-group, randomised trial. Lancet Respir Med. 2026. doi:10.1016/S2213-2600(26)00191-8.
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