Inclusion of the Number of Metastatic Lymph Nodes in the Staging System for Medullary Thyroid Cancer: Validating a Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System

Background: The current American Joint Committee on Cancer (AJCC) staging system (8th edition) for medullary thyroid cancer (MTC) was originally extrapolated from the staging system for differentiated thyroid cancer. However, the current staging system does not accurately predict the prognosis of patients with MTC. Patients and Methods: The present study was based on data from the Surveillance, Epidemiology, and End Results (SEER) database and validated by multicenter data from the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Xuzhou City Central Hospital, and Suzhou Ninth People's Hospital. Hazard ratio with its 95% confidence interval [CI] was estimated by Cox proportional hazards regression analysis. The concordance index (C-index) was used to evaluate the discrimination accuracy of the current AJCC tumor-node-metastasis (TNM) staging system and the modified AJCC (mAJCC) TNM staging system. Results: A total of 1175 MTC patients were selected from the SEER database and 312 from the three hospitals in China. We redefined the N category according to the number of metastatic lymph nodes (LNs) as follows: N'0 category (0 metastatic LNs), N'1 category (1-9 metastatic LNs), and N'2 category (≥10 metastatic LNs). The four distinct tumor stages were reclassified in the mAJCC staging system as follows: stage I (T1-4N'0M0, T1N'1M0), stage II (T2-3N'1M0, T1N'2M0), stage III (T4N'1M0, T2-4N'2M0), and stage IV (TanyN'anyM1). The C-index of the current AJCC staging system and the mAJCC staging system was 0.72 [CI, 0.67-0.78] and 0.78 [CI, 0.73-0.84], respectively. Similar results were observed in the survival analysis of the multicenter data set. Conclusions: The mAJCC staging system could discriminate the prognosis of MTC patients more effectively than the current AJCC staging system, indicating that it is feasible and appropriate to modify the current AJCC staging system by introducing the number of metastatic LNs instead of the location of LNs. These findings might be adopted in the next edition of the AJCC staging system and be used to guide clinical practice.