The Diagnostic Yield of Cone Beam CT Combined With Radial-Endobronchial Ultrasound for the Diagnosis of Peripheral Pulmonary Nodules: Systematic Review and Meta-Analysis.

Background: Identification of peripheral pulmonary nodules (PPNs) is becoming increasingly common with modern imaging and lung cancer screening programs. Navigational bronchoscopy has been developed to augment the diagnostic yield of sampling these nodules. Cone beam CT (CBCT) scan is one navigational tool which can be used alongside the historical criterion standard of fluoroscopy and radial endobronchial ultrasound (r-EBUS). Research Question: What is the diagnostic yield and safety profile of combining CBCT scan with r-EBUS for the diagnosis of PPNs? Study Design and Methods: Embase, PubMed, and Cochrane Central Register of Controlled Trials were searched in March 2023. Eligible studies used CBCT scan with r-EBUS as the primary navigation technique. The primary outcome, diagnostic yield, was analyzed using random effects meta-analysis. Additional subgroup analysis was based on the use of additional navigational technologies. Risk of bias was assessed using the Critical Appraisal Skills Programme tool for diagnostic studies. The Grading of Recommendations Assessment, Development, and Evaluation tool was used to assess the quality of outcomes. Results: Fourteen studies (865 patients and 882 lesions) were included. The risk of bias was significant as assessed using the Critical Appraisal Skills Programme tool, which identified multiple confounders. The pooled diagnostic yield of combined CBCT scan and r-EBUS-guided biopsy for the diagnosis of PPNs was 80% (95% CI, 76%-84%). Subgroup analysis of diagnostic yield for CBCT scan and r-EBUS alone was 80% (95% CI, 76%-83%). The diagnostic yield of CBCT scan and r-EBUS combined with additional navigational technology (electromagnetic navigational bronchoscopy, virtual bronchoscopic navigation, and robotic-assisted bronchoscopy) was 80% (95% CI, 73%-87%). The quality of outcomes was assessed as low to very low using the Grading of Recommendations Assessment, Development, and Evaluation tool. There was a 2.01% pneumothorax rate and 1.08% bleeding rate. Although heterogeneously reported, the total radiation dose was between 19.59 and 85.9 Gy.cm Interpretation: CBCT scan and r-EBUS for the diagnosis of PPNs has a high diagnostic yield and acceptable safety profile. Studies showed moderate heterogeneity with significant bias; hence, generalizability of the study is limited and further prospective trials are required. Clinical Trial Registration: PROSPERO; No.: CRD42023410221; URL: https://www.crd.york.ac.uk/prospero/.