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Review
. 2025 Mar 31;14(3):991-1006.
doi: 10.21037/tlcr-24-974. Epub 2025 Mar 14.

Multidisciplinary management of N2 stage III non-small cell lung cancer: opportunities and challenges for radiation oncology

Affiliations
Review

Multidisciplinary management of N2 stage III non-small cell lung cancer: opportunities and challenges for radiation oncology

Hongcheng Zhu et al. Transl Lung Cancer Res. .

Abstract

Stage III non-small cell lung cancer (NSCLC) constitutes a heterogeneous ailment, with optimal treatment evolving. This is especially true in N2 disease, where definitive treatment is often a discussion of surgery versus definitive chemoradiotherapy (CRT). New developments in neoadjuvant and adjuvant systemic therapeutics have shifted treatment paradigms, emphasizing the importance of multidisciplinary team discussions. The recent revisions to the ninth edition of the American Joint Commission on Cancer (AJCC) staging system have prompted a realignment in nodal stage categorization, introducing refined subcategories of N2 disease (N2a and N2b), which enhance prognostic accuracy. Critical questions including defining resectability and operability, feasibility of definitive CRT for operable patients, radiotherapy in operative and non-operative disease, and advanced radiation technology for definitive CRT are needed to be considered and answered in clinical practice. The current review aims to present a comprehensive overview of radiation oncology in management of N2 stage NSCLC by summarizing key clinical trials as well as most advanced evidence, including defining resectability and operability, feasibility of definitive CRT for operable patients, radiotherapy in operative and non-operative disease, and advanced radiation technology for definitive CRT. The review summarizes the most recent evidence and insights for radiation oncologists and other specialists involved in the multidisciplinary thoracic oncology team, to provide a better understanding of the opportunities and challenges for radiotherapy in the management of N2 stage III NSCLC.

Keywords: N2; Non-small cell lung cancer (NSCLC); radiotherapy; stage III.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-974/coif). A.V.L. serves as an unpaid editorial board member of Translational Lung Cancer Research from November 2024 to October 2026. S.L.G. has received research funding from AstraZeneca, Boehringer Ingelheim, Roche, MSD, Amgen and Daiichi Sankyo; received honoraria from AstraZeneca; and participated on Advisory Board for Pfizer and MSD. V.G. has received personal fees as a speaker and/or as an advisory board member from Roche, Astrazeneca, MSD; and received grants from the Italian Health Ministry for PRIN research projects of significant national interest-call 2022. R.F. has received consulting fees from AMCA. A.V.L. has received honoraria from AstraZeneca for advisory board and speaker’s bureau. The other authors have no conflicts of interest to declare.

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