Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification
Authors: Pan Jian-Ji , Mai Hai-Qiang , Ng Wai Tong , Hu Chao-Su , Li Jin-Gao , Chen Xiao-Zhong , Chow James C. H. , Wong Edwin , Lee Victor , Ma Ling-Yu , Guo Qiao-Juan , Liu Qin , Liu Li-Zhi , Xu Ting-Ting , Gong Xiao-Chang , Qiang Meng-Yun , Au Kwok-Hung , Liu Tsz-Chim , Chiang Chi Leung , Xiao You-Ping , Lin Shao-Jun , Chen Yun-Bin , Guo Shan-Shan , Wong Charlene H. L. , Tang Lin-Quan , Xu Zhi-Yuan , Jia Yi-Zhen , Peng Wen-Sa , Hu Li-Ping , Lu Tian-Zhu , Jiang Feng , Cao Cai-Neng , Xu Wei , Ma Jun , Blanchard Pierre , Williams Michelle , Glastonbury Christine M. , King Ann D. , Patel Snehal G. , Seethala Raja R. , Colevas A. Dimitrios , Fan Dai-Ming , Chua Melvin L. K. , Huang Shao Hui , O’Sullivan Brian , Lydiatt William , Lee Anne W. M. 
Published: October 2024

Importance

Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential.

Objective

To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC.

Design, Setting, and Participants

This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9).

Main Outcomes and Measures

The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping.

Results

Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, &amp;gt;3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects.

Conclusion and Relevance

The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.