Protocol for the Veterans Affairs Cooperative Studies Program Study Number 2005: A Phase 3 Randomized Trial of Lung Cancer Surgery or Stereotactic Radiotherapy for Operable Early-Stage Non-Small Cell Lung Cancer
Background: Standard-of-care treatment options for stage I non-small cell lung cancer (NSCLC) include surgery and stereotactic body radiation therapy (SBRT). Notwithstanding a lack of prospective evidence demonstrating superior long-term survival with either of these treatments, evidence-based guidelines currently recommend only surgery for patients with operable disease and to limit SBRT for patients with inoperable disease. Research Question: Do surgery or SBRT lead to superior survival rates for operable stage I NSCLC? Study Design and Methods: A phase 3 randomized clinical trial was designed to compare the overall survival (OS) rates after surgery or SBRT for stage I NSCLC. Eligible participants must have biopsy-confirmed NSCLC measuring ≤ 5 cm in maximum diameter located > 1 cm from the trachea, proximal bronchial tree, esophagus, and spinal cord. Participants must be staged with fluorodeoxyglucose PET scans with mandatory biopsies of all radiographic areas concerning for regional or distant metastatic disease. The planned accrual is 670 patients to detect a 10% absolute benefit in 5-year OS with surgery or SBRT. Secondary outcome measures include patient-reported quality of life, respiratory function, health state utilities, patterns of lung cancer relapse, and causes of mortality by independent adjudication. Results: The study was initiated in April 2017 with a planned ramp-up phase at six Veterans Affairs medical centers. Adapted recruitment interventions contributed to overcoming historical barriers to randomizing eligible participants between surgery and SBRT, and the study was expanded to 16 sites in May 2019. As of July 5, 2023, 280 of 670 planned participants have been enrolled. Interpretation: The final results are expected to clarify the role of SBRT in lieu of surgery for patients with operable stage I NSCLC and to facilitate more informed discussions about these treatment options. Trial Registry: ClinicalTrials.gov; No.: NCT02984761; URL: www.clinicaltrials.gov
