Preliminary diagnostic performance of probe-based confocal laser endomicroscopy for peripheral pulmonary nodules, a multicenter prospective registry trial

Background: Current bronchoscopic methods to diagnose Peripheral Pulmonary Nodule (PPN) have a low yield and high false negative rate. Probe-based Confocal Laser Endomicroscopy (pCLE) enables in-vivo real-time visualization of alveolar microstructure during navigational bronchoscopy. Objectives: This primary objective was to identify and to validate pCLE criteria for the diagnosis of malignant PPN. Methods: Patients with suspicious PPN were recruited prospectively in a multicenter trial. Navigational bronchoscopy was performed to guide the pCLE probe and video images were recorded prior to transbronchial biopsy (TBB). Seven pCLE criteria were identified by expert pulmonologists and validated in a blinded fashion with a standard TBB histopathology. A linear regression combining pCLE criteria with the pre-test nodule malignancy calculation (PNMC) score based on CT, demographics and clinical data was performed. Results: 70 patients (73 PPN) were enrolled in six centers. pCLE criteria were conclusive in 72% of the cases compared to TBB. Complete loss of tissue architecture was identified as the most accurate and reproducible pCLE criterion predicting malignancy. Combining pCLE findings to PNMC significantly improved the sensitivity from 0.67 to 0.92, the negative predictive value from 0.65 to 0.88, the accuracy from 0.68 to 0.82 and the area under the receiver operating curve from 0.74 to 0.87. There were three technical failures (4.3%) and three small pneumothoraces (4.3%) not attributed to pCLE. Conclusions: pCLE criteria could improve the performance of the pre-test probability of PPN malignancy.