In patients with early-stage non–small cell lung cancer (NSCLC) eligible for either surgery or stereotactic ablative radiotherapy (SABR), surgical resection was associated with significantly lower 3-year all-cause mortality, according to findings from an emulated target trial reported by Kagenaar et al in the Journal of Clinical Oncology. However, the difference in mortality was smaller and not statistically significant among patients aged 80 years or older, suggesting that SABR may be a reasonable curative-intent alternative in this population.
Study Details
Investigators used linked data from England’s National Cancer Registry, Hospital Episode Statistics, and the National Radiotherapy Data Set to compare outcomes following SABR and surgical resection in patients diagnosed with T1–2N0M0 NSCLC between January 2015 and December 2020. Eligible patients were aged 18 to 79 years with a Zubrod performance status of 0 to 2, or aged 80 years or older with a performance status of 0 to 1. Treatment was initiated within 6 months of diagnosis.
The analysis included 12,546 patients, of whom 2,299 (18.3%) received SABR and 10,247 (81.7%) underwent surgical resection. Patients receiving SABR were generally older, frailer, and more likely to have comorbidities than those undergoing surgery. The primary endpoint was 3-year all-cause mortality; secondary endpoints included lung cancer–specific mortality and disease recurrence.
Key Results
After adjustment, estimated 3-year all-cause mortality was 30.3% following SABR vs 21.6% following surgical resection, representing an absolute risk difference of 8.8 percentage points (95% confidence interval [CI] = 1.4–16.2; P = .02). At 2 years, estimated all-cause mortality was 21.1% vs 13.7%, respectively (absolute risk difference = 7.4 percentage points; 95% CI = 0.9–13.8; P = .02). The difference at 1 year was not statistically significant.
Estimated 3-year lung cancer–specific mortality was also higher following SABR than surgery (20.6% vs 14.5%), although the difference did not reach statistical significance (absolute risk difference = 6.1 percentage points; 95% CI = –0.6 to 12.9; P = .07). Similarly, estimated 3-year recurrence rates were 34.3% vs 27.9% (absolute risk difference = 6.5 percentage points; 95% CI = –1.7 to 14.6; P = .12). In contrast, 90-day hospital readmissions were numerically less frequent following SABR (23.3% vs 30.2%; P = .07).
Subgroup analyses showed that the difference in 3-year all-cause mortality was smaller among patients aged 80 years or older, all of whom had a performance status of 0 or 1. In this subgroup, the absolute risk difference was 4.3 percentage points (95% CI = –3.7 to 12.3; P = .62), compared with 10.9 percentage points among patients aged 18 to 69 years and 8.4 percentage points among those aged 70 to 79 years.
The investigators also observed that the mortality difference between SABR and surgery narrowed over the study period. Alternative analyses generally supported the primary findings.
“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,” they concluded.
Richard Grieve, PhD, of the Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Institute for Health and Care Research. For full disclosures of the study authors, visit ascopubs.org.
