NASHVILLE — The FROSTBITE-2 randomized trial found that a 1.1-millimeter cryoprobe achieved a higher diagnostic yield and fewer complications than traditional 2.0-millimeter forceps in transbronchial lung biopsies. Among 500 patients randomly assigned to either method, the cryoprobe produced a diagnostic yield of 88.6% compared to 78.8% with forceps.
In a subgroup of patients with pulmonary nodules or masses, the cryoprobe yielded a diagnosis in 83.2% of cases, while forceps succeeded in 70.1%. The trial was conducted at nine U.S. medical centers that perform at least 100 transbronchial biopsies annually and have affiliated centers specializing in lung cancer, lung transplant, and interstitial lung disease.
A secondary safety analysis showed that four patients in the forceps group (1.6%) experienced pneumothorax requiring chest tube placement, while none occurred in the cryoprobe group. No cases of bleeding or respiratory failure were reported in either group during the trial.
The 1.1-millimeter cryoprobe used in the study is small enough to retrieve tissue through the bronchoscope’s working channel without withdrawing the scope. Earlier studies using a larger 1.9-millimeter cryoprobe produced higher-quality specimens but were linked to more bleeding and pneumothorax events.
Although certain lots of the cryoprobe underwent a U.S. Food and Drug Administration Class I recall in March 2026 due to reports of rupturing during activation, no such incidents occurred during the FROSTBITE-2 trial. The study was an investigator-initiated trial funded by Erbe, a surgical systems manufacturer, which had no role in trial design, data analysis, or publication decisions. The research was conducted under the auspices of the Interventional Pulmonary Outcomes Group.
"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 biopsy," said Fabien Maldonado, Professor of Medicine and Thoracic Surgery. He added, "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." Maldonado also stated, "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."
Robert Lentz, Associate Professor of Medicine and Thoracic Surgery, said, "These results bring us one step closer to making these vital diagnostic procedures even more safe, accurate and effective."