Predictive Value of Clinicopathological Factors to Guide Post-Operative Radiotherapy in Completely Resected pN2-Stage III Non-Small Cell Lung Cancer

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC).Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome.Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1-3 positive lymph nodes, and a positive-to-dissected lymph node ratio <= 0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment.