ABSTRACT: Background and Objectives: The research on the therapeutic effect of preoperative radiotherapy (PRRT) for patients with early non-small cell lung cancer (NSCLC) is still insufficient, and the impact of postoperative radiotherapy (PORT) on the prognosis of patients with early NSCLC remains controversial. We conducted this study to investigate the effect of PORT and PRRT on prognosis for these patients. Materials and Methods: In total, 3640 patients with stage II NSCLC who underwent a lobectomy or pneumonectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression was adopted to identify the independent influence of PORT or PRRT on patients' prognosis. Subgroup analysis of survival was performed in patients with different combinations of key clinical features. We also used Kaplan-Meier analysis and competitive risk analysis to explore to which extent PORT or PRRT impacted the overall survival and cumulative mortality. Results: PORT was an independent risk factor of NSCLC-specific death among patients with N0 stage (HR, 1.648; 95% CI, 1.309-2.075, p < 0.001) and in N1 stage with <3 positive lymph nodes (HR, 2.698; 95% CI, 1.910-3.812, p < 0.001) in multivariate analysis. Findings from subgroup analysis for the risk of NSCLC-specific death, competitive risk analysis of NSCLC-specific cumulative mortality, and overall survival analysis also demonstrated PORT was detrimental to patients in these two subgroups above (p < 0.05). However, in patients with N1 stage with ≥3 positive lymph nodes, PORT may help prolong median survival. PRRT was an independent risk factor for NSCLC-specific death in multivariate analysis of patients with N0 stage (HR, 1.790; 95% CI, 1.201-2.668, p = 0.004), and significantly decreased overall survival in these patients (p < 0.001). Conclusion: PORT is associated with worse survival outcome and better cumulative mortality of stage II patients of NSCLC with N0 disease or N1 disease (<3 nodes), while PRRT is associated with reduced prognosis in patients with N0 stage. On the other hand, PORT may help to improve the prognosis of patients with N1 stage who have three or more lymph node metastases. Hence, PORT and PRRT should not be recommended for patients with N0 stage. However, in patients with "high volume" N1 stage, PORT might improve oncological outcomes.
