Global Proposal for the TNM Staging System for Poorly Differentiated Thyroid Cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: Importance: Poorly differentiated thyroid cancer (PDTC) lacks a dedicated staging system, requiring use of the eighth version of the American Joint Committee on Cancer and Union for International Cancer Control TNM staging system (TNM-8) for differentiated thyroid cancer despite its distinct biology. Objective: To develop a PDTC-specific staging system. Design, Setting, and Participants: This cohort study analyzed data from the International Aggressive Thyroid Cancer Collaborative Group (IATCCG), including surgically treated patients at 91 centers in 14 countries from January 1984 to January 2026. External validation was performed using patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Data were analyzed from December 2025 to June 2026. Main Outcomes and Measures: The primary end point was overall survival. With M1 disease predefined as stage IVB, the schema for stages I-IVA in patients with M0 disease were redefined. All possible TN combinations were fitted into multivariable Cox models, with the lowest Akaike information criterion defining the proposed system. Prognostic discrimination was assessed using adjusted hazard ratios (aHRs) and C statistics. Results: Among 1010 patients in the IATCCG cohort, 610 (60.4%) were female, and the median (IQR) age at diagnosis was 58 (46-68) years; median (IQR) follow-up was 41 (15-85) months. Among 170 patients in the SEER cohort, 85 (50.0%) were female, and the median (IQR) age at diagnosis was 61 (49-72) years; median (IQR) follow-up was 92 (42-154) months. In the IATCCG cohort, level VII lymph node metastasis (LNM) was associated with lower 5-year overall survival (45.2%; 95% CI, 33.4-61.2) than level VI (73.2%; 95% CI, 64.4-83.3) or lateral neck LNM (56.7%; 95% CI, 49.4-65.0). Level VII LNM was therefore reclassified from N1a to N1c. The lowest Akaike information criterion configuration among 16 738 candidates defined stages I to IVA as follows: I, T1N0/NX/N1a or T2N0/NX; II, T1N1b/N1c, T2N1a/N1b, or T3N0/NX/N1a; III, T2N1c, T3N1b, or T4aN0/NX/N1a; IVA, T3N1c, T4aN1b/N1c, or T4b any N; and IVB, M1 disease. Compared with TNM-8, stage I disease decreased from 44.4% (448 of 1010) to 24.6% (248 of 1010) and stage IV disease increased from 18.5% (187 of 1010) to 32.4% (327 of 1010) with the proposed system. The proposed staging had a higher C statistic than TNM-8 (0.74 [95% CI, 0.71-0.76] vs 0.71 [95% CI, 0.68-0.74]; difference, 0.03; 95% CI, 0.01-0.04). Corresponding SEER C statistic values were 0.76 (95% CI, 0.71-0.81) vs 0.74 (95% CI, 0.68-0.79), respectively (difference, 0.02; 95% CI, -0.01 to 0.06). Conclusions and Relevance: This cohort study found that this PDTC-specific staging system provides improved prognostic stratification reflecting its different biology. These data provide a strong rationale for the potential inclusion of a stand-alone American Joint Committee on Cancer staging system for PDTC.
Source: JAMA Oncology
Authors: Xiao Shi, Qiaomu Liu, Daniel Scholfield, Dapeng Li, Livia Lamartina, Shuwei Chen, Hao Zhang, Alexander J. Papachristos, Omar Hamdy, Natalia Timofeeva, Amy Sheen, Xiangqian Zheng, Ming Song, Zhihong Wang, Xianying Meng, Lei Xie, Detao Yin, Ying Zheng, Shangtong Lei, Christoph Becker, Ekin Y. Koroglu, Fangzhou Liu, Jie Ming, Tianrun Liu, Hui Liu, Hengyu Li, Zhendong Li, Xingrui Li, Xinying Li, Jian Xu, Yijun Wu, Bo Zhang, Meiping Shen, Yansong Lin, Linzi Jia, Zhilong Ai, Dapeng Lei, Zhiyan Liu, Haixia Guan, Chuang Chen, Haipeng Xiao, Yihao Liu, Zhihui Li, Dongmei Ji, Qinghai Ji, Luis G. Carvajal-Carmona, Ana Patricia Estrada-Florez, Mabel E. Bohórquez, Matrix Man Him Fung, Martin Schlumberger, Lori Wirth, Louise Davies, Fabian Pitoia, Nelson Wohllk, João Martins Gama, Tommaso Porcelli, Domenico Salvatore, Mira Fink, Berna Evranos Ogmen, Eun Kyung Lee, Andrea Repaci, Giovanni Tallini, Cosimo Durante, Simone De Leo, Laura Fugazzola, Ilya Sleptsov, Young Joo Park, Mohamed-Amine Bani, Ian Ganly, Anthony J. Gill, Yu Wang, International Aggressive Thyroid Cancer Collaborative Group, Yulong Wang, Julien Hadoux, Stanley B Sidhu, Mark S Sywak, Arseny A Semenov, Bekir Cakir, Ankui Yang, Jiapeng Huang, Kehao Le, Weihao Liu, Zhengchao Wei, Shitong Yu, Yanbin Zhao, Yajing Zhou, Yu Guo, Shuping Wu, Chaoqian Liu, Huilei Dong, Yaying Du, Hui Ouyang, Yongbiao Luo, Cuiwei Li, Chenyi Wang, Kaiyi Niu, Qijun Li, Wei Liu, Tongliang Xia, Xindan Zhang, Rili Gao, Deguang Kong, Jiaye Liu, Anggi Vélez-Bohórquez, Carlos Eduardo Jiménez-Canizales, Maria João Martins, Matteo Trevisan, Guowei Zhang, Hailin Xi, Yefeng Cai, Hongzhong Zhou, Anbing Dong, Hui Hua, Chao Qin, Jianfeng Sang, Gang Li, Shanting Liu, Hao Pi, Yuan Sheng, Xiaolong Zhao, Bin Li, Jianhong Ye, Jian Tang, Huaguo Wu, Wanjun Chen, Qingxia Wang, Xiaowei Peng, Jiahao Pan, Wei Zhang, Wenxin Zhao, Mengxin Zhang, Na Li, Tingting Zhang, Xiaopeng Ma, Yuntao Song, Bin Zhang, Fu Luo, Yan Xu, Chen Chen, Yiting Jin, Lu Zhang, Junwen Bai, Yang Li, Xing Sun, Chen Li, Kewei Jiang, Xuhang Zhu, Jinbiao Shang, Lunhua Guo, Susheng Miao, Nan Feng, Xucai Zheng, Erica Solaroli, Xiaohua Tai, Xueyong Zheng, Jiawei Feng, Yong Jiang, Yuyuan Ma, Xiaomin Gu, Chunlian Li, Deyuan Fu, Liang Sun, Enqiao Yu, Qin Li, Mengshi Chi, Kepeng Zhu, Junyuan Lv, Shibo Liang, Yuantong Shi, Qiulan Chen, Chunlan He, Linkun Zhong, Ming Gao, Ruochuan Cheng, Minghua Ge, Shaoyan Liu, Changming An
Institutions: Shanghai Medical College of Fudan University, Fudan University, Fudan University Shanghai Cancer Center, Memorial Sloan Kettering Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Université Paris-Saclay, Institut Gustave Roussy, Sun Yat-sen University, Sun Yat-sen University Cancer Center, First Hospital of China Medical University, The University of Sydney, Royal North Shore Hospital, Mansoura University, Mansoura University Hospital, St Petersburg University, First Hospital of Jilin University, Sir Run Run Shaw Hospital, Zhejiang University, First Affiliated Hospital of Zhengzhou University, Jilin Province Tumor Hospital, Nanfang Hospital, Southern Medical University, University of Freiburg, University Medical Center Freiburg, Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Jiangsu Cancer Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital, Fujian Provincial Cancer Hospital, Second Military Medical University, Changhai Hospital, Sichuan University, West China Hospital of Sichuan University, China Medical University, Xiangya Hospital Central South University, Tongji Hospital, Tumor Hospital of Guangxi Medical University, First Affiliated Hospital Zhejiang University, China-Japan Friendship Hospital, Jiangsu Province Hospital, Nanjing Medical University, Peking Union Medical College Hospital, Shanxi Provincial Cancer Hospital, Zhongshan Hospital, Qilu Hospital of Shandong University, Shanghai Jiao Tong University, Shanghai Sixth People's Hospital, Guangdong Provincial People's Hospital, Renmin Hospital of Wuhan University, The First Affiliated Hospital, Sun Yat-sen University, University of California, Davis, Universidad del Tolima, University of Hong Kong, Harvard University, Massachusetts General Hospital, Mass General Brigham, University of Wisconsin–Madison, Universidad de Buenos Aires, Hospital del Salvador, University of Chile, Unidade Local de Saúde de Coimbra, University of Naples Federico II, National Cancer Center, University of Bologna, Sapienza University of Rome, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Seoul National University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225386106