What Does N2 Lymph Node Involvement Mean for Patients with Non-Small Cell Lung Cancer (NSCLC)?—A Review of Implications for Diagnosis and Treatment

Patients with stage III NSCLC with N2 lymph node involvement carry a complex and diverse disease entity. Challenges persist in the areas of diagnosis, staging, multimodal management, and the determination of surgical indications and resectability criteria. Therefore, this review focuses on the latest updates in N2 disease staging and its prognostic and treatment implications. Emphasis is placed on the importance of accurate staging using imaging modalities such as [18F]FDG-PET/CT as well as minimally invasive mediastinal staging endoscopic techniques. The evolving role of surgery in the management of N2 disease is also explored. The benefits of neoadjuvant and adjuvant treatments have been demonstrated, along with the efficacy of a combined multimodal approach with chemo-immunotherapy in the perioperative setting, reigniting the debate of N2 disease subsets and optimal treatment options. Furthermore, this review addresses the controversies surrounding surgical approaches in upfront “borderline” resectable stage III NSCLC as well as the benefits of combined chemoradiotherapy with consolidation immunotherapy for patients with unresectable tumors. In conclusion, personalized diagnostic and treatment approaches tailored to individual patient characteristics, resource availability, and institutional expertise are essential for optimizing outcomes in patients with stage III-N2 NSCLC.