Radial Endobronchial Ultrasound-guided Transbronchial Cryobiopsy versus Forceps Biopsy for the Diagnosis of Solitary Pulmonary Nodules: A Prospective Randomised Trial

Michael Brown1, 2, *, Phan Nguyen1, 2, Hubertus Jersmann1, 2, Mark Holmes1, 2, Michelle Wong1, 3
1 Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia
2 Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, Australia
3 Department of Respiratory and Sleep Medicine, Lyell McEwin Hospital, Adelaide, Australia

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 259
Abstract HTML Views: 111
PDF Downloads: 122
ePub Downloads: 70
Total Views/Downloads: 562
Unique Statistics:

Full-Text HTML Views: 135
Abstract HTML Views: 62
PDF Downloads: 76
ePub Downloads: 47
Total Views/Downloads: 320

Creative Commons License
© 2023 Brown et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Thoracic Medicine, Royal Adelaide Hospital 1 Port Road, Adelaide SA 5000, Australia;
Tel: +61 8 7074 0000; E-mail:



Improvements in pulmonary diagnostic imaging and the development of lung cancer screening are increasing the prevalence of Solitary pulmonary nodules (SPNs). Fluoroscopically guided radial endobronchial ultrasound (EBUS) with transbronchial forceps biopsy (TB-FB) has been the conventional diagnostic method. Transbronchial cryobiopsy (TB-CB) is an alternative biopsy method. We sought to compare transbronchial cryobiopsy to transbronchial forceps biopsy for the diagnosis of SPNs.


A prospective, single-centre, randomised controlled trial was conducted at the Royal Adelaide Hospital (RAH). Patients with SPNs were randomised to either 5 transbronchial forceps biopsies or one transbronchial cryobiopsy. Complete blinding of investigators and participants was not possible, as transbronchial cryobiopsy required general anaesthesia. The primary outcome was diagnostic yield with secondary outcomes of specimen size, diagnostic yield for subsets challenging to access with forceps and safety.


The overall diagnostic yield for the 28 enrolled subjects was 76.8%(22/28). The diagnostic yield was 91.7% (11/12 patients) for transbronchial cryobiopsy and 68.8% (11/16 patients) for forceps biopsy (p=0.14). Median biopsy sizes were consistently larger for the cryobiopsy arm at 7.0mm compared to 2.5mm(p<0.0001). An eccentric EBUS image signalling the probe was adjacent to the nodule occurred in 4/28 cases, and TB-CB confirmed a diagnosis in 3/3 randomised to this arm. There were no major complications with either technique.


Transbronchial cryobiopsy under the guidance of fluoroscopy and radial EBUS facilitates larger biopsy specimens without a significant increase in major complications. Further research is required to confirm the effect on diagnostic yield; however, our study supports a role for TB-CB in the diagnosis of SPNs and small, nodule-adjacent biopsies.

Clinical Trial Registration Number:

Reference number of R20160213(HREC/16/RAH/37).

Keywords: Endobronchial ultrasound, Transbronchial cryobiopsy, Cryobiopsy, Solitary Pulmonary Nodule, Lung cancer, Peripheral pulmonary nodule.