From operable to systemic: The role of surgery in the era of immunotherapy?

Introduction: The development of immunotherapy and advanced radiotherapy techniques has significantly changed the treatment paradigm for non-small cell lung cancer (NSCLC). The traditional role of surgery as the primary treatment modality in early-stage disease is now being redefined within a multimodal approach. The aim: Analyses the contemporary role of surgery in the era of immunotherapy, with a particular focus on perioperative strategies, integration of radiotherapy, and the importance of biomarkers in patient selection. Methods: A review of current literature and key clinical trials investigating neoadjuvant and perioperative immunotherapy, including CheckMate 816 and KEYNOTE-671, with an analysis of surgical outcomes and pathological response. Results: Perioperative immunotherapy leads to a significant increase in pathological complete response (pCR) and major pathological response (MPR), along with improved event-free survival. At the same time, stereotactic body radiotherapy (SBRT) and radioimmunotherapy expand therapeutic options, particularly in inoperable and oligometastatic patients. However, neoadjuvant therapy introduces new surgical challenges, including fibrosis, altered anatomical planes, and an increased risk of complications. Biomarkers such as PD-L1 expression and circulating tumor DNA (ctDNA) are becoming essential tools for therapy personalization. Conclusion: Surgery remains a key component in the treatment of NSCLC, but within a selective and individualized multimodal approach. The integration of immunotherapy, radiotherapy, and biomarker-driven strategies is redefining the indications and timing of surgical treatment. The future lies in adaptive therapeutic models based on tumor biology and multidisciplinary decision-making.