Advanced Robotic Techniques and Rapid Onsite Evaluation for Minimally Invasive Diagnosis and Next-Generation Sequencing.

Pulmonary nodules are an incredibly common finding, with millions incidentally detected in the US every year. Biopsy is often needed for diagnosis. Robotic assisted bronchoscopy (RAB) with integrated cone beam computed tomography (CBCT) has achieved diagnostic yields exceeding 80% in some studies, significantly higher than traditional methods without advanced imaging, due to the added ability to correct alignment of the bronchoscopy catheter with the target lesion in real-time. Given this, the added value of rapid on-site cytologic evaluation (ROSE) with modern bronchoscopy is an area of debate. ROSE involves immediate intraprocedural microscopic assessment of biopsy specimens (typically by a cytotechnologist) to confirm adequacy of biopsy samples for malignant diagnosis during the bronchoscopy. This study will aim to test the hypothesis that modern bronchoscopy done without ROSE guidance is non-inferior to bronchoscopy with ROSE available. Patients undergoing RAB to biopsy a lung lesion will be approached for enrollment and assigned to either ROSE vs no ROSE if they agree to participate. Randomization will be revealed before procedures are started. All decisions regarding procedure tools, techniques, and patient management will be per usual care and at the discretion of the treating physician.

• Rapid onsite evaluation (Other): ROSE involves immediate intraprocedural microscopic assessment of biopsy specimens (typically by a cytotechnologist) to confirm adequacy of biopsy samples for malignant diagnosis during the bronchoscopy

Primary outcomes

• Strict diagnostic yield, defined as the proportion of procedures that result in acquisition of lesional tissue. [7 days post procedure]: Lesional tissue is defined by the presence of specific pathological findings that readily explain the presence of a pulmonary lesion. The following common pathological findings are pre-specified: 1. Malignancy 2. Specific benign pathologic findings including: organizing pneumonia, frank purulence/robust neutrophilic inflammation with a pathogen isolated, granulomatous inflammation, hamartoma, amyloidoma or other uncommon causes of peripheral pulmonary lesions with distinctive pathological patterns.

Secondary outcomes

• Sufficiency of malignant specimens for Next-Generation Sequencing [30 days post procedure]: Proportion of malignant biopsies with sufficient material to send for NGS

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* ≥ 18 years of age at time of bronchoscopy
* Undergoing robotic assisted bronchoscopy to biopsy a pulmonary lesion

Exclusion Criteria:

* Declines to participate or inability to provide informed consent.
* Clinician determination that the use of ROSE is required or contraindicated for the optimal care of an individual patient
* Patient enrolled in another trial that requires ROSE for PPL biopsy
* Patient previously consented for this trial
* Pregnant or incarcerated patients

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• Fabien Maldonado, MD, Principal investigator, Vanderbilt University Medical Center