Navigational Bronchoscopy vs CT Scan-Guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: Protocol and Rationale for the Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study Multicenter Randomized Trial

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant causes. The gold standard for minimally invasive biopsy, CT scan-guided transthoracic needle biopsy (CT-TTNB), has not been compared directly with navigational bronchoscopy, a method that recently has seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rates. Current estimates of the diagnostic usefulness of both methods are based largely on noncomparative data with significant risk for selection, referral, and publication biases. Research Question: Is contemporary navigational bronchoscopy noninferior to CT scan-guided transthoracic needle biopsy for the diagnosis of indeterminate pulmonary nodules? Study Design and Methods: Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study, is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10 to 30 mm in diameter with before testing probability of malignancy of at least 10%. The primary end point is diagnostic accuracy through 12 months of follow-up. Secondary end points include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Results: This article describes the protocol and rationale for the Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study, designed to answer the study question. Interpretation: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity that often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are reviewed centrally by an independent interventional pulmonology and radiology adjudication panel relying on prespecified exclusions to ensure enrolled nodules are amenable to sampling by both methods while protecting against selection bias favoring either method. Conservative diagnostic yield and accuracy definitions with prespecified criteria for what nonmalignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic usefulness. Trial Registry: ClinicalTrials.gov; No.: NCT04250194; URL: www.clinicaltrials.gov