Comparison of Survival Rates After a Combination of Local Treatment and Systemic Therapy vs Systemic Therapy Alone for Treatment of Stage IV Non–Small Cell Lung Cancer

IMPORTANCE: As many as 55% of patients with non–small cell lung cancer (NSCLC) present with stage IV disease at diagnosis. Although systemic therapy is the cornerstone for treatment of these patients, growing evidence suggests that local treatment of the primary tumor site may improve survival. OBJECTIVE: To assess whether addition of local treatment for primary tumor site in stage IV NSCLC provides a survival benefit over systemic therapy alone. DESIGN, SETTING, AND PARTICIPANTS: In this comparative effectiveness research study, the National Cancer Database (NCDB; 2018 version) was retrospectively queried from January 1, 2010, through December 31, 2015, for patients with a histopathologic diagnosis of stage IV NSCLC. Exclusion criteria were being younger than 18 years and missing information on tumor characteristics and follow-up data. Data were analyzed from November 1, 2018, through January 1, 2019. EXPOSURES: Treatment groups were stratified as (1) surgical resection plus systemic therapy; (2) external beam radiotherapy (EBRT) or thermal ablation (TA; including cryosurgery and radiofrequency ablation) plus systemic therapy; and (3) systemic therapy alone. MAIN OUTCOMES AND MEASURES: Overall survival was compared between treatment groups using multivariable Cox proportional hazards regression models and after propensity score matching. Subgroup analyses were planned a priori according to patient and tumor characteristics. RESULTS: A total of 34 887 patients met inclusion criteria (19 002 male [54.5%]; median age, 68 years [interquartile range, 60-75 years]), among whom 835 underwent surgical resection plus systemic therapy; 9539, EBRT/TA plus systemic therapy; and 24 513, systemic therapy alone. Demographic and cancer-specific factors were associated with treatment allocation with a higher likelihood of surgical resection for oligometastatic NSCLC. After multivariable adjustment, surgical resection was associated with superior overall survival compared with EBRT/TA or systemic therapy alone (hazard ratio [HR] for EBRT/TA, 0.62; 95% CI, 0.57-0.67; P < .001; HR for systemic therapy alone, 0.59; 95% CI, 0.55-0.64; P < .001). Treatment with EBRT/TA demonstrated superior overall survival compared with systemic therapy alone (HR, 0.95; 95% CI, 0.93-0.98; P = .002). Interaction analyses identified heterogeneous associations with treatment; the EBRT/TA survival benefit was especially pronounced in stage IV squamous cell carcinoma with limited T and N category disease and oligometastases (HR, 0.68; 95% CI, 0.57-0.80; P < .001), with overall survival rates of 60.4% vs 45.4% at 1 year, 32.6% vs 19.2% at 2 years, and 20.2% vs 10.6% at 3 years for combination therapy vs systemic therapy alone. CONCLUSIONS AND RELEVANCE: In stage IV NSCLC, surgical resection or EBRT/TA of the primary tumor site may provide survival benefits in addition to systemic therapy alone in selected patients. Specifically, EBRT/TA may be considered as a treatment option in select patients who are ineligible for surgical resection.