Global Proposal for the TNM Staging System for Poorly Differentiated Thyroid Cancer

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.

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Journal
JAMA Oncology
Published
2026-11-06
DOI
https://doi.org/10.1001/jamaoncol.2026.4705
Primary Topic
Thyroid Cancer Diagnosis and Treatment
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article

Global Proposal for the TNM Staging System for Poorly Differentiated Thyroid Cancer

Omar Hamdy, Zhendong Li, Amy Sheen, Tommaso Porcelli et al.
2 links
JAMA Oncology
Thyroid Cancer Diagnosis and Treatment
article

Global Proposal for the TNM Staging System for Poorly Differentiated Thyroid Cancer

Omar Hamdy, Zhendong Li, Amy Sheen, Tommaso Porcelli, Christoph Becker, Huilei Dong, Simone De Leo, Alexander Papachristos, Qinghai Ji, Luis G. Carvajal‐Carmona, Mabel Elena Bohórquez L, Shangtong Lei, Andrea Repaci, Mohamed Amine Bani, Lori J. Wirth, Ana Patricia Estrada-Florez, Anthony James Gill, Meiping Shen, Mark S. Sywak, Martin Jean Schlumberger, Domenico Salvatore, Mira Fink, Cosimo Durante, Laura Fugazzola, Fabián Pitoia, Kehao Le, Daniel William Scholfield, João Martins Gama, Haixia Guan, Berna Evranos Ogmen, Dongmei Ji, Matrix MH Fung, Julien Hadoux, Livia Lamartina, 赵炎斌, Ian Ganly, Nelson Wohllk G, Tianrun Liu, Louise Davies, Yang Ankui, Natalia Timofeeva, Giovanni Tallini, Ying Zheng, Семенов Арсений Андреевич, Bo Zhang, Hui Liu, Fangzhou Liu, Linzi Jia, Zhilong Ai, Dapeng Lei, Detao Yin, Yongbiao Luo, Zhou Yajing, Stanley B. Sidhu, Илья Слепцов, Cuiwei Li, Hengyu Li, Xiao Shi, Shuwei Chen, Dapeng Li, Chenyi Wang, Ming Song, Shuping Wu, Zhihong Wang, Jian Xu, Yihao Liu, Qiaomu Liu, Wei Liu, Shitong Yu, Yu Guo, Xingrui Li, Young Joo Park, Lei Xie, Chaoqian Liu, Jiapeng Huang, Hui Ouyang, Xiangqian Zheng, Kaiyi Niu, Yu Wang, Zhihui Li, Zhiyan Liu, Chuang Chen, Xindan Zhang, Qijun Li, Zhengchao Wei, Tongliang Xia, Xianying Meng, Haipeng Xiao, Yulong Wang, Xinying Li, Ekin Y. Koroglu, Yansong Lin, Yaying Du, Eun Kyung Lee, Bekir Cakir, Hao Zhang, Jie Ming, International Aggressive Thyroid Cancer Collaborative Group, Weihao Liu, Yijun Wu
article en

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.

JAMA Oncology
The University of Sydney (AU), Memorial Sloan Kettering Cancer Center (US), Shanghai Medical College of Fudan University (CN), University of Wisconsin–Madison (US), Harvard University (US), Seoul National University (KR), Sun Yat-sen University (CN), Mansoura University (EG), University of Freiburg (DE), St Petersburg University (RU), Second Military Medical University (CN), Shanghai Jiao Tong University (CN), University of Milan (IT), Sichuan University (CN), Universidad de Buenos Aires (AR), Fudan University (CN), Université Paris-Saclay (FR), Royal North Shore Hospital (AU), China-Japan Friendship Hospital (CN), Peking Union Medical College Hospital (CN), University Medical Center Freiburg (DE), Institut Gustave Roussy (FR), Hospitais da Universidade de Coimbra (PT), Sir Run Run Shaw Hospital (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Universidad del Tolima (CO), Massachusetts General Hospital (US), West China Hospital of Sichuan University (CN), Mansoura University Hospital (EG), Fudan University Shanghai Cancer Center (CN), Sun Yat-sen Memorial Hospital (CN), Jilin Province Tumor Hospital (CN), Hospital del Salvador (CL), Shanxi Provincial Cancer Hospital (CN), Nanfang Hospital (CN), Changhai Hospital (CN), National Cancer Center (KR), First Hospital of Jilin University (CN), Zhongshan Hospital (CN), Jiangsu Cancer Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), Wuhan Union Hospital (CN), Renmin Hospital of Wuhan University (CN), First Hospital of China Medical University (CN), Shanghai Sixth People's Hospital (CN), Sun Yat-sen University Cancer Center (CN), Fujian Provincial Cancer Hospital (CN), Ankara Yıldırım Beyazıt University (TR), Jiangsu Province Hospital (CN), Guangdong Provincial People's Hospital (CN), Tumor Hospital of Guangxi Medical University (CN), First Affiliated Hospital of Zhengzhou University (CN), Xiangya Hospital Central South University (CN), Tongji Hospital (CN), Qilu Hospital of Shandong University (CN), First Affiliated Hospital Zhejiang University (CN), Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo (IT), Ankara Bilkent City Hospital (TR), Huazhong University of Science and Technology (CN), Mass General Brigham (US), Southern Medical University (CN), University of Chile (CL), University of Naples Federico II (IT), Zhejiang University (CN), Nanjing Medical University (CN), University of California, Davis (US), Sapienza University of Rome (IT), University of Hong Kong (HK), China Medical University (CN), University of Bologna (IT)
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