Postoperative Radiotherapy in Patients with Completely Resected Non-small Cell Lung Cancer: Exploring Optimal Local Treatment Strategies Involving Surgery and Radiotherapy

<p>Among adjuvant therapies for completely resected non-small cell lung cancer (NSCLC), postoperative platinum-based adjuvant chemotherapy has been a standard of care. While postoperative radiotherapy (PORT), as an important option for treating local lesions, has been expected to be able to reduce local recurrence and further improve both the disease-free survival (DFS) and overall survival (OS) for a long period, benefit of PORT for the DFS or OS has not been verified yet, despite promoting locoregional control. In particular, a detrimental effect of PORT was observed in patients with pathological N0-1 stage I-II NSCLC. In contrast, several retrospective studies have demonstrated that PORT improved the survival of patients with pathological N2 (pN2) stage III NSCLC, proving to be a promising therapy for those patients. Regarding surgery, about 20% of patients with pN2 stage III NSCLC develop recurrence inside the systematic nodal dissection area. Accordingly, locoregional control by surgery alone seems to be insufficient. In 2021, two randomized, phase III clinical trials (Lung ART and PORT-C) revealed that PORT improved locoregional control, although this did not translate to a significant gain in the survival. Therefore, PORT still cannot be recommended as a standard treatment in patients with pN2 stage III NSCLC. A randomized phase III trial (JCOG1916: J-PORT) involving PORT for pN2 NSCLC patients with adjuvant chemotherapy is currently underway in Japan and might bring further insight in the future. At present, molecular-targeted therapies and immunotherapies are being studied in the adjuvant setting, and immune checkpoint inhibitors have been adopted as an adjuvant therapy for patients with completely resected stage II-IIIA NSCLC. In this setting, the role of PORT merits further exploration. Given that radiotherapy and immunotherapy can synergistically activate anti-tumor immunity, PORT concomitantly or sequentially combined with immunotherapy might be a promising potential treatment modality.</p>