Development of a New TNM Staging System for Poorly Differentiated Thyroid Carcinoma: a Multicenter Cohort Study

Yu Guo¹Qianyi Zhong¹Liangen Xie¹Xudong Wang²Liang Guo³Shimin Zhuang¹Feng Pang¹Chunyan Jia⁴Lijiao Wu¹Jin Peng^5,6Ankui Yang^5,6*Tianrun Liu^7*

• ¹The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
• ²Department of Maxillofacial Otorhinolaryngology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin, China
• ³Department of Head & Neck Surgery, Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, Zhejiang Province, China
• ⁴Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
• ⁵Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
• ⁶State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guanghzou, Guangdong, China
• ⁷Department of Thyroid Surgery, Sun Yat-sen Memorial Hospital, Guangzhou, China

Objective Poorly differentiated thyroid cancer (PDTC) is a rare, heterogeneous carcinoma from follicular cells, characterized by poor differentiation, aggressive spread, and poor prognosis. Currently, there is no specific staging system for PDTC. This study aimed to develop a new TNM staging system tailored to PDTC for improved disease management. Methods A new TNM staging system was designed and internally validated using data from the US SEER database (2004-2016) on PDTC cases. External validation was performed using data from four major institutions in China. Prognostic factors influencing cancer-specific survival (CSS) were identified through Cox regression analyses. Patients were stratified into subgroups based on adjusted hazard ratios (AHRs), weighted by these prognostic factors. The new system classified patients into five stages with distinct 5-year CSS outcomes. Results The study analyzed 1,201 PDTC cases from SEER and 85 cases from China. Among the 876 patients in the training cohort, the new TNM staging system showed superior discrimination compared to the 8th edition of the AJCC TNM system. The 5-year CSS rates for the new stages I, II, III, IVA, and IVB were 96.3%, 88.4%, 69.4%, 43.3%, and 22.3%, respectively. The new system outperformed the 8th edition in predicting CSS, as shown by time-dependent ROC curves, C-index, and calibration plots. Both internal and external validation confirmed its predictive abilities. Conclusion The current AJCC staging system inadequately predicts PDTC prognosis. The new TNM staging system developed in this study offers improved stratification and prognosis prediction, potentially guiding more effective clinical management for PDTC.