Stereotactic Ablative Radiotherapy Versus Surgical Resection for Early-Stage Non–Small Lung Cancer: An Emulated Target Trial

Purpose Stereotactic ablative radiotherapy (SABR) is standard of care for inoperable early-stage non–small cell lung cancer (NSCLC), but there is little evidence to support SABR as an alternative to surgical resection. Randomized controlled trials (RCTs) have failed to recruit, and ongoing RCTs apply strict inclusion criteria. To our knowledge, this is the first emulated target trial comparing the effectiveness of SABR versus surgery in individuals with early-stage NSCLC eligible for either treatment. Methods We used England's National Cancer Registry data to identify individuals diagnosed with T1-2N0M0 NSCLC during 2015-2020, age 18-79 years with Zubrod performance status 0-2, or age 80+ years with performance status 0-1, who underwent SABR or surgical resection within 6 months of diagnosis. Treatment receipt was identified via linkage to Hospital Episode Statistics and the National Radiotherapy Data Set. The primary outcome was 3-year all-cause mortality; secondary outcomes included lung cancer–specific mortality and recurrence. An instrumental variable analysis reduced the risk of confounding by indication. Results A total of 12,546 met the eligibility criteria (2,299 SABR; 10,247 surgery). After adjustment, 3-year all-cause mortality estimates were 30.3% (SABR) and 21.6% (surgery; mean absolute risk difference 8.8 percentage points [pp], [95% CI, 1.4 to 16.2]; P = .02). Lung cancer–specific mortality estimates were 20.6% (SABR) and 14.5% (surgery; mean absolute risk difference 6.1 pp [95% CI, –0.6 to 12.9]; P = .07). The adjusted mean absolute risk difference in 3-year all-cause mortality for those age 80+ years was 4.3 pp ([95% CI, –3.7 to 12.3]; P = .62). Conclusion This emulated target trial found higher 3-year all-cause mortality after SABR versus surgery in early-stage NSCLC suitable for either modality, supporting that surgical resection should remain the preferred option. The findings support SABR as a curative-intent alternative, particularly for older people.