In select patients with stage IV non-small cell lung cancer (NSCLC), the addition of surgical resection or external beam radiotherapy (EBRT)/thermal ablation (TA) of the primary tumor site to systemic therapy may result in improved survival, according to study results published in the JAMA Network Open.

A total of 34,887 adult patients with a histopathologic diagnosis of stage IV NSCLC from the National Cancer Database (2018 version) were included in this retrospective study. Researchers compared data from patients who received either surgical resection plus systemic therapy (n=835), EBRT or TA (ie, cryosurgery and radiofrequency ablation) plus systemic therapy (n=9539), or systemic therapy alone (n=24,513). The groups were compared in terms of overall survival using multivariable Cox proportional hazards regression models and following propensity score matching.

Surgical resection was more likely to be used for patients with adenocarcinoma and N0 to N1 category disease, whereas patients with squamous cell carcinoma were more likely to receive EBRT/TA. Patients with limited local spread and multiple systemic metastases were more likely to receive systemic therapy plus EBRT/TA and systemic therapy alone.

In the adjusted analysis, the overall survival was better for surgical resection vs EBRT/TA (hazard ratio [HR], 0.62; 95% CI, 0.57-0.67; P <.001) or systemic therapy alone (HR, 0.59; 95% CI, 0.55-0.64; P <.001). Additionally, the use of EBRT/TA was superior to systemic therapy alone in terms of overall survival (HR, 0.95; 95% CI, 0.93-0.98; P =.002).

Patients with stage IV squamous cell carcinoma with limited T and N category disease and oligometastases experienced more pronounced overall survival benefit with EBRT/TA (HR, 0.68; 95% CI, 0.57-0.80; P <.001). The 1-year overall survival rates for EBRT/TA vs systemic therapy alone were 60.4% vs 45.4%, respectively. Additionally, combination therapy conferred an overall survival rate of 32.6% vs 19.2% with systemic therapy alone at 2 years and 20.2% vs 10.6% for systemic therapy alone at 3 years.

Limitations of the study included the retrospective nature as well as the lack of data on the NSCLC mutational statuses of the patients, the latter of which could have led to an imbalance in actionable mutations between treatment groups.

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The researchers concluded that while their results suggest that surgical resection is more often used in patients with small, oligometastatic NSCLC, “patients beyond this selected cohort might benefit from surgical resection.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Uhlig J, Case MD, Blasberg JD, et al. 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. JAMA Netw Open. 2019;2(8):e199702.