Abstract Patients with severe Chronic Obstructive Pulmonary Disease (COPD) often present with pulmonary nodules suspicious for early-stage lung cancer but cannot safely undergo biopsy or surgical resection due to poor pulmonary reserve. This creates a clinical dilemma: whether to pursue empiric definitive therapy, such as stereotactic body radiotherapy (SBRT), or to observe and treat only upon progression. Historically, untreated presumed lung cancers in this high-risk group progress rapidly with dismal survival, emphasizing the need for alternative management strategies. We systematically searched MEDLINE/PubMed, Embase, and the Cochrane Library (through September 2025) for studies comparing SBRT versus observation in severe COPD (GOLD III-IV or ppoFEV1 ≤40%); patients with “biopsy infeasible” pulmonary nodules due to hypoxemia, pneumothorax risk, anticoagulation, or poor reserve. English-language studies of any design reporting outcomes such as overall and cancer-specific survival, tumor control, or toxicity were included. Two reviewers independently screened and extracted data, and study quality was assessed. Results were summarized descriptively due to study heterogeneity. Seven retrospective or registry studies (n 55,000) met inclusion criteria, all analyzing clinically early-stage, medically inoperable lung cancer. Across studies, SBRT consistently produced superior outcomes compared with observation. Adjusted hazard ratios for mortality ranged from 0.56 to 0.64 (p 0.001), indicating a two- to three-fold improvement in survival. Three-year overall survival increased from ∼20% with observation to ∼40-50% with SBRT; 5-year survival improved from ∼6-10% to ∼25-30%. Median survival rose from about 1 year (observation) to 3 years (SBRT). Lung cancer-specific survival was markedly higher, with one study reporting 85% 5-year cancer-specific survival after SBRT versus 16% with observation. Local tumor control after SBRT exceeded 90% at 3-5 years, while untreated nodules nearly always progressed. About half of SBRT-treated patients remained progression-free at 5 years. SBRT was well tolerated, with no treatment-related 30-day mortality and 5% incidence of severe (grade ≥3) toxicity. Grade 2 pneumonitis occurred in ∼5-10% of patients, and average pulmonary function declined only modestly; the quality of life was generally preserved. In contrast, most patients initially managed with observation later required palliative radiation or chemotherapy as disease advanced. In severe COPD patients with presumed early-stage lung cancer who cannot undergo biopsy, empirical SBRT substantially improves survival and disease control compared with observation. It can double or triple life expectancy with minimal morbidity, supporting SBRT as the preferred definitive therapy when tissue diagnosis is not feasible. This abstract is funded by: None
Christian et al. (Fri,) studied this question.