Bhargava, Rohan

Abstract Introduction Multiple pulmonary nodules (MPNs) are commonly encountered in patients at elevated risk for thoracic malignancy and represent a spectrum of disease states and stages. We evaluated the safety, and procedural outcomes of a combined robotic assisted bronchoscopy (RaB) and linear endobronchial ultrasound (EBUS) approach to patients with MPNs during a single bronchoscopic procedure. Methods This multicenter observational registry included patients who underwent RaB for evaluation of MPNs. Data were prospectively collected from six centers between 2019 and 2025. Demographics, imaging characteristics, safety events, and procedural outcomes were analyzed and associated with final diagnosis. Results A total of 191 patients underwent RaB with biopsy of MPN during a single procedure; 167 patients also underwent linear EBUS lymph node sampling. The strict per nodule diagnostic yield was 71.5% overall (first nodule 70.7%, second 74.3%, third 71.4%). At least one malignant nodule was identified in 127 patients (66.8%), and 85 patients (44.5%) had two or more malignant nodules; 15 patients (17.6%) demonstrated heterogeneous histopathology between malignant nodules. Among patients with non–small cell lung cancer, adequate cellularity for next generation sequencing was achieved in 82.6% of nodules. Malignant lymph nodes were identified in 10.8% (18/167). No patients with two pure ground glass nodules (0/8) had malignant nodal involvement. Pneumothorax occurred in 7.3% of cases, with 2.1% requiring chest tube placement; unplanned admissions occurred in 3.7%. Conclusion This study provides a large multisite registry evaluation of performance of simultaneous bronchoscopic sampling of multiple pulmonary nodules with EBUS staging during a single anesthesia event demonstrating an acceptable safety profile and adequacy for molecular profiling.

8049 Background: Multiple pulmonary nodules (MPN) pose significant challenges for accurate staging of non-small cell lung cancer (NSCLC). As next generation sequencing (NGS) technologies have become more widely available on smaller amounts of tissue, the prevalence and clinical implications of heterogeneity between MPNs are poorly understood. This study retrospectively evaluates the histopathological and NGS findings after MPN biopsy in a single robotic-assisted bronchoscopy (RaB) procedure. Methods: 191 patients were retrospectively enrolled at 6 geographically diverse centers in the US. All patients had 2+ pulmonary nodules biopsied and staging EBUS in the same procedure. An expert molecular pathologist reviewed NGS data between nodule pairs to determine if they were discordant, concordant, or indeterminate. Results: Of 191 patients, 85 patients had 2 malignant nodules with 15 of those demonstrating histopathologic heterogeneity (e.g., one adenocarcinoma, one squamous cell carcinoma). 26 patients with 2 malignant nodules of similar histopathology demonstrated molecular heterogeneity between nodules. These cases were reviewed by an expert molecular pathologist who determined the following breakdown: -15 discordant pairs (57.7%) -3 concordant pairs (11.5) -8 indeterminate pairs (30.8%) Breakdown by nodule density: -Discordant: 7 same density, 8 different density -Concordant: 3 same density -Indeterminate: 5 same density, 3 different density Breakdown by nodule laterality: -Discordant: 7 ipsilateral, 8 contralateral -Concordant: 2 ipsilateral, 1 contralateral -Indeterminate: 4 ipsilateral, 4 contralateral Staging EBUS was performed in all 26 cases with malignancy identified in 2 cases. NGS sufficiency for NSCLC from three sites with standardized NGS reporting was as follows: 1 st nodule biopsied: 42/54 (77.8%), 2 nd nodule biopsied: 37/51 (72.5%), 3 rd nodule biopsied: 2/4 (50%). In total, 90/109 (82.6%) NSCLC samples had adequate tissue for NGS. In 85 cases with 2 malignant nodules, 35 (41.2%) had all nodules Stage IIB or lower. Notably, 25 (29.4%) of the cases did not have NGS available on one or more of the nodules, thus precluding staging. Conclusions: This study highlights the frequency and clinical relevance of histopathologic and molecular heterogeneity among synchronous MPNs. Importantly, heterogeneity was not limited to contralateral or anatomically distant lesions, challenging the assumption that spatial proximity implies clonal relatedness. Further, this study shows that relying solely on density or radiographic features of a nodule is an incomplete discriminator between separate primary lung cancers and intrapulmonary metastasis. Our findings support the need for an integrated diagnostic paradigm in which sampling of multiple lesions is used to inform clonality, refine staging, and guide precision therapy.