Small Cryoprobe Outperforms Forceps in Lung Biopsy Trial

Accurate diagnosis of pulmonary nodules, post-transplant allograft dysfunction, and diffuse parenchymal lung disease depends on high-quality tissue obtained during bronchoscopy. Conventional forceps biopsy can crush small samples and may lower diagnostic yield, while pneumothorax and bleeding remain procedural concerns. Clinicians need methods that raise accuracy without increasing risk in routine transbronchial lung biopsy. A new randomized study reports higher diagnostic yield using a cryoprobe compared with forceps to help address this challenge.

The FROSTBITE-2 randomized trial, conducted within the Interventional Pulmonary Outcomes Group, enrolled 500 adults across nine U.S. medical centers, including Vanderbilt Health. Researchers from Vanderbilt University Medical Center compared a 1.1-millimeter cryoprobe with 2.0-millimeter forceps during transbronchial lung biopsy for pulmonary nodules or masses, recent lung transplant, and diffuse parenchymal lung disease. The findings were published in JAMA on May 18 2026.

Transbronchial lung biopsy advances a bronchoscope through the upper airway to peripheral targets. A cryoprobe uses localized freezing to adhere to and extract tissue while preserving architecture. Forceps pinch tissue for removal but can crush specimens. The 1.1-millimeter cryoprobe is small enough to retrieve the sample through the bronchoscope’s working channel without removing the scope, a feature that increases procedural safety.

Diagnostic yield reached 88.6% with the 1.1-millimeter cryoprobe versus 78.8% with 2.0-millimeter forceps, a nearly 10-point difference. Among patients with pulmonary nodules or masses, yield was 83.2% with cryoprobe and 70.1% with forceps. Safety outcomes favored cryobiopsy: pneumothorax requiring chest tube occurred in 1.6% of forceps biopsies and in none of the cryoprobe cases. No significant bleeding or respiratory failure events occurred in either group.

Prior work with a 1.9-millimeter cryoprobe produced larger, higher-quality specimens but was linked to more bleeding and pneumothorax. The present results suggest the smaller 1.1-millimeter device may mitigate those risks while maintaining yield. Certain lots of the cryoprobe underwent a Food and Drug Administration (FDA) Class I recall in March due to reports of rupture during activation; no such events occurred in this trial.

“A structurally intact, sufficiently large tissue sample from a targeted area in the lung increases the likelihood of an accurate diagnosis, which is what we strive for every time we perform a transbronchial lung biops,” said interventional pulmonologist Fabien Maldonado, MD, MSc, Professor of Medicine and Thoracic Surgery, and Director of Interventional Pulmonology at the Vanderbilt Lung Institute.

"We're continually investigating ways we can improve these procedures, as accurate diagnoses up-front save time, which may help get patients the treatment they need faster. Evaluating the tools we use, particularly as innovations in this area occur, is an important avenue of investigation. Individuals who have known or suspected lung issues deserve to have the best possible diagnostic procedures, so they and their clinical teams have clear evidence of what is occurring in their lungs so informed treatment decisions can be made," added Dr. Maldonado.

“These promising results bring us one step closer to making these vital diagnostic procedures even more safe, accurate and effective. Our team is currently conducting FROSTBITE-3, a randomized controlled trial comparing the 1.1-millimeter cryoprobe with instruments for lymph node biopsies, to determine whether this novel tool may help with molecular testing in patients diagnosed with lung cancer,” said Robert Lentz, MD, Associate Professor of Medicine and Thoracic Surgery at Vanderbilt Health.

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