BACKGROUND: Due to demographic shifts, the population is aging, and patients are experiencing more comorbidities. Stereotactic body radiotherapy (SBRT) offers high rates of local control for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC). However, obtaining histopathological confirmation can be challenging due to severe comorbidities, small tumors, or unfavorable anatomical locations. METHODS: Between 2011 and 2022, we retrospectively analyzed a cohort of patients who underwent lung SBRT for presumed early-stage NSCLC at our institution. Out of 486 consecutive patients treated during this period, 56 patients (11.5%) with a total of 61 lesions were identified and included in this retrospective study. All included patients lacked histopathological confirmation prior to treatment and had no evidence of other active malignancies. The primary objective of this analysis was to evaluate pulmonary function tests before and after SBRT, including long-term follow-up. RESULTS: The median overall survival (OS) after empiric SBRT was 50.7 months (95% confidence interval [CI] 12.8-88.7). Survival rates at 1 year and 2 years were 88.4 and 71.1%, respectively. The 1‑, 2‑ and 3‑year local control rates were 96.6%, 92.3% and 87.1%. Pulmonary function tests indicated a relative increase in the mean forced expiratory volume in 1 s (FEV1) of 0.55% (SD 13.5) and 2.0% (SD: 20.0) at 6 and 12 months, respectively. In contrast, the mean diffusing capacity of the lungs for carbon monoxide (DLCO) showed a relative decline of 7.4% (SD 16.6) and 6.3% (SD 26.1) at 6 and 12 months, respectively. Patients with lower comorbidity scores (CCI
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