International Initiative on a Refined Staging System for Medullary Thyroid Cancer: A Multinational Multicenter Study
Xiao Shi, Qiaomu Liu, Bin Xu, Dapeng Li, Antonio Matrone, Julien Hadoux, Ian Ganly, Benjamin Houot, Xiangqian Zheng, Nelson Wohllk, Bekir Cakir, Giovanni Tallini, Omar Hamdy, Mira Fink, Fabian Pitoia, João Martins Gama, Luis G. Carvajal-Carmona, Quoc Dat Ngo, Domenico Salvatore, Alexander J. Papachristos, Stanley B. Sidhu, Leonardo Rossi, Brian R. Untch, Andreas Spörlein, Quoc Thang Pham, Cenkai Shen, Hao Zhang, Kehan Song, Yijun Wu, Zhiyan Liu, Kewei Jiang, Chenyi Wang, Haipeng Xiao, Simone De Leo, Mabel E. Bohórquez, Ana Patricia Estrada-Florez, Berna Evranos Ogmen, Ekin Yigit Koroglu, Qinghai Ji, Dongmei Ji, Martin Schlumberger, Lori Wirth, Rossella Elisei, Ilya V. Sleptsov, Young Joo Park, Laura Fugazzola, Mohamed-Amine Bani, Ronald A. Ghossein, Anthony J. Gill, Yu Wang, , Gabriela Sansó, Amy Sheen, Angela Y. Pan, Mark S. Sywak, Javiera Arancibia, Jesus Veliz, Pablo Guzman, Changming An, Chuang Chen, Cuiwei Li, Haixia Guan, Han Luo, Hanqing Liu, Lei Ye, Liang Guo, Miao Mo, Ming Gao, Ming Song, Minghua Ge, Peng Li, Shaoyan Liu, Wenjun Wei, Wuyang Ji, Yan Zhang, Yansong Lin, Yihao Liu, Yuan Li, Yulong Wang, Zhihong Wang, Zhihui Li, Zijie Niu, Anggi Vélez-Bohórquez, Carlos Eduardo Jiménez-Canizales, Christoph Becker, Andrea Repaci, Cosimo Durante, Cristina Luongo, Gabriele Materazzi, Matteo Trevisan, Moon Young Oh, Maria João Martins, Arseny A. Semenov, Louise Davies, Anh Tu ThaiPURPOSE
To refine the suboptimal prognostic discrimination of the American Joint Committee on Cancer (AJCC) 8th edition TNM (TNM-8) staging system for medullary thyroid carcinoma (MTC).
METHODS
This retrospective study enrolled patients with MTC from 43 centers across 15 countries under the framework of the International Medullary Thyroid Cancer Staging Consortium (IMTCSC). Pooled data were analyzed with disease-specific survival as the primary end point. With M1 disease fixed in stage IVC, we redefined the schema for stages I to IVB in M0 patients. Using exhaustive enumeration, all possible TN combinations were fitted into multivariable Cox models, with the lowest Akaike information criterion (AIC) defining the proposed system. Prognostic discrimination was assessed using adjusted hazard ratios (aHRs) and the concordance index (C-index).
RESULTS
The IMTCSC cohort included 2,573 patients with MTC (female-to-male ratio: 1.25; median age 52 years [IQR, 41-62]; median follow-up 76.3 months [IQR, 37.3-121.0]). Level VII metastasis correlated with poorer survival, supporting its upgrade to N1c. Exhaustive search of 116,284 admissible stage-grouping schemas identified the optimal model (lowest AIC) defining stages I to IVB: I (T1N0-N1a/T2N0), II (T1N1b/T2N1a/T3N0), III (T1N1c/T2N1b/T3N1a/T4aN0-N1a), IVA (T2N1c/T3N1b-N1c/T4aN1b), and IVB (T4aN1c/T4b any N). Compared with AJCC TNM-8 (stage I as reference; stage II aHR, 0.84,
CONCLUSION
The proposed MTC staging system confers an improved schema for prognostic stratification compared with AJCC TNM-8.