Validation of the Role of Postoperative Radiotherapy in Improving Disease-Free Survival of Patients with Stage III ypN2 Non-Small Cell Lung Cancer after Neoadjuvant Therapy Followed by Complete Resection – A Propensity-Score Matching Study

Abstract

<h3>Purpose/Objective(s)</h3> Although the Lung ART study, a phase III trial, showed that postoperative radiotherapy (PORT) could not significantly improve the disease-free survival (DFS) of patients with pN2 non-small cell lung cancer (NSCLC) after complete resection. However, its subgroup analysis showed that PORT did significantly improve the DFS of those with ypN2 NSCLC after neoadjuvant therapy and surgery. Our study aimed to validate the effect of PORT on the survival of patients with ypN2 NSCLC. <h3>Materials/Methods</h3> Patients was filtrated from our center from 2004 to 2021. The inclusion criteria of patients were as follows: 1) diagnosed with NSCLC; 2) accepted neoadjuvant systematic treatments including chemotherapy, tyrosine kinase inhibitors (EGFR, ALK), or immune checkpoint inhibitors; 3) received complete resection (R0 resection); 4) with stage III ypN2 disease (AJCC 8^th). We excluded patients with multiple primary malignant tumors and those who died within four months after surgery. The primary endpoint was DFS. The second endpoints were overall survival (OS) and locoregional recurrence-free survival (LRFS). Propensity-score matching (PSM) was used to match the baseline characteristics between the PORT group and the non-PORT group. Kaplan-Meier method was used to estimate the endpoints. All data were analyzed using R 4.1.2. <h3>Results</h3> Totally 185 patients were included in the final analysis. There were 49 patients (26.5%) with PORT. After 1:1 PSM between the PORT group and the non-PORT group, 82 patients remained with 41 in each group. The baseline characteristics of majority in the matched cohort were as follows: male (75.6%), smoking history (79.3%), performances scores 0-1 (100%), adenocarcinoma (47.6%), grade 3-4 (58.5%), receiving neoadjuvant chemotherapy (91.5%), lobectomy (82.9%), ypT1-2 (78.9%), and ypN2b (51.2%). The median age of patients was 58. The median numbers of examined and positive lymph nodes were 20.5 and 6. The median follow-up time was 49.5 months. The median DFS of the PORT group and the non-PORT group were 25.5 months vs. 18.6 months, with the 5-year DFS rates of 43.4% vs. 24.8%, respectively (P=0.044). The median LRFS of the two groups were not reached vs. 56.8 months, with the 5-year LRFS rates of 89.1% vs. 39.8% (P<0.001). The median OS of the two groups were not reached vs. 67.7 months, with the 5-year OS rates of 76.7% vs. 34.8% (P=0.092). <h3>Conclusion</h3> For patients with stage III ypN2 NSCLC after neoadjuvant systematic therapy followed by complete resection, PORT can significantly improve the DFS and LRFS, but failed to improve OS. However, the results need to be clarified by prospective randomized clinical trials.