Advances in Multimodality Management of Localized NSCLC.

Abstract

Lung cancer represents the most common cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) comprising the vast majority of cases. Outcomes for stage II-III NSCLC remain suboptimal due to late presentation, biological heterogeneity, and limited efficacy of traditional therapies. Recent advances have reshaped the therapeutic landscape, with immunotherapy and targeted treatments now integrated into the management of resectable NSCLC. Landmark trials such as CheckMate 816 demonstrated improved event-free and overall survival with neoadjuvant chemoimmunotherapy approaches. Similarly, adjuvant targeted therapies such as osimertinib and alectinib have shown benefit in patients with EGFR and ALK alterations, respectively. This review provides an overview of evolving diagnostic strategies, highlights pivotal clinical trials, and explores multidisciplinary treatment approaches across stages I to III NSCLC. We also address key challenges including optimal treatment sequencing, patient selection, and duration of therapy. As clinical trial data continue to mature, personalized multimodal strategies guided by molecular and clinical features remain central to improving long-term outcomes in resectable NSCLC.