Outcomes For Nsclc Patients Treated With Empiric Sbrt Are Similar To Patients With Biopsy-Proven Disease

Early stage non-small cell lung cancer (NSCLC) is becoming more common, often found via screening or incidentally. These patients often have substantial comorbidities which limit their ability to have a biopsy and/or surgical resection. Increasingly, such patients are treated empirically with SBRT for presumed early stage NSCLC without definitive pathologic diagnosis, based on clinical/radiologic findings. A recent meta-analysis of empiric SBRT studies for NSCLC emphasizes the need for more rigorous investigation. All patients treated with SBRT for early stage (T1-3N0) NSCLC at a single institution from 2008-2018 were retrospectively analyzed. Patients were standardly staged with PET/CT scans (98%), index lesions biopsied by bronchoscopy or CT-guided approach (74%) and treated with SBRT 48-60Gy in 3-5 fractions. Empiric SBRT was recommended for lesions that likely represented NSCLC by lesion growth, FDG avidity on PET/CT and clinical characteristics based on multidisciplinary tumor board consensus. We estimated overall (OS), disease-free (DFS), regional DFS and distant metastasis-free (DMFS) survival as well as local control (LC) using Kaplan-Meier method and compared patients with biopsy-proven (pathologic cohort) versus those without a definitive biopsy (empiric cohort) with a two-sided log-rank test. Our review identified 211 lesions treated in 170 patients with primarily peripherally located T1N0 NSCLC. Of these, 55 lesions were treated empirically (25 with a nondiagnostic biopsy, and 30 with no attempted biopsy), and 156 lesions were included in the pathologic cohort. Patients were treated to a median SBRT dose of 48 Gy in 4 fractions; dose did not differ between the cohorts (p = 0.21). Lesions in the empiric cohort had lower Mayo and Brock malignancy risk scores (p = 0.055 and p = 0.0007, respectively), suggesting lower malignancy risk based on clinical history and imaging. Despite this, 3-year OS (∼64%), DFS (∼49%), regional DFS, DMFS and LC were similar between the two cohorts (HR 0.88-1.12). Thirty- and 90-day mortalities after SBRT were low in the cohort overall: 0.47% and 0.95%, respectively. Among the 173 lesions biopsied prior to SBRT, bronchoscopy was used in 98 (57%) and CT-guided biopsy in 75 (43%). Thirty-eight of these 173 patients (22%) had a complication requiring hospital admission. Complications were more common in patients undergoing a CT-guided biopsy (25/75; 33%) than bronchoscopic biopsy (13/98; 13%). Pneumothorax was the most common complication (31/173; 18%), followed by wheezing/bronchospasm/hypoxemia (6/173; 3.5%). Patients with early stage NSCLC treated empirically with SBRT have similar outcomes to patients with biopsy-proven disease, with a very low rate of toxicity. This suggests that empiric SBRT is a reasonable approach for patients who are unfit for biopsy or have a nondiagnostic biopsy.