| Summary: | <b>Background/Objectives</b>: Patients with non-small cell lung cancer (NSCLC) being evaluated for stereotactic body radiation therapy (SBRT) are frequently staged non-invasively with positron emission tomography/computed tomography (PET/CT). Performing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in addition to PET/CT scanning may increase clinical certainty in lymph node staging, but the magnitude of added benefit of EBUS-TBNA over non-invasive staging methods is unclear. <b>Methods</b>: A single-center prospective cohort study involving patients with suspected or confirmed Stage I or IIa NSCLC referred for EBUS-TBNA prior to SBRT was performed. The primary outcome was concordance between PET/CT and EBUS-TBNA for nodal metastases. Secondary endpoints included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT, and clinical outcomes based on staging results. <b>Results</b>: Among 115 patients, the concordance between PET/CT and EBUS-TBNA was 84.3% (95% CI: 0.76 0.90). EBUS-TBNA led to a stage shift in 15.7% of cases: 4 of 98 PET/CT N0 patients (4.1%) had nodal metastases, while 14 of 17 PET/CT N1 patients (82.4%) were downstaged to N0. PET/CT sensitivity was 42.9% (95% CI: 0.09–0.81), specificity 87% (95% CI: 0.79–0.93), PPV 17.6% (95% CI: 0.04–0.43), and NPV 95.9% (95% CI: 0.90–0.99). PET/CT-positive, EBUS-TBNA-negative patients had worse survival (HR 4.25, 95% CI: 1.24–14.53, <i>p</i> = 0.021) compared with double-negative patients. <b>Conclusions</b>: EBUS-TBNA improves staging accuracy over PET/CT in early-stage NSCLC, impacting SBRT candidacy. However, PET/CT-positive, EBUS-TBNA-negative patients had worse outcomes in comparison to double-negative patients, suggesting a need for additional therapy or surveillance in that population.
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