Role of Postoperative Radiotherapy in Pathologic Stage IIIA (N2) Non-Small Cell Lung Cancer in a Prospective Nationwide Oncology Outcomes Database

Abstract

Introduction: The role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database.

Methods: Patients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization.

Results: A total of 2691 patients were identified, with a median follow-up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson-Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR = 0.83, 95% CI [confidence interval]: 0.72-0.95; p = 0.008). This benefit remained significant after CBPS weighting (HR = 0.81, 95% CI: 0.70-0.94, p = 0.005), almost significant after landmark analysis (adjusted HR = 0.84, 95% CI: 0.69-1.007, p = 0.059), and significant after landmark analysis with CBPS weighting (HR = 0.77, 95% CI: 0.63-0.94, p = 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non-PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson-Deyo comorbidity index, and grade (all p < 0.05).

Conclusions: Improved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.

Keywords: Chemotherapy; Lung; Radiation; Surgery.