A critical analysis of the current TNM classification for differentiated thyroid carcinoma in young patients: Time for a change?

BACKGROUND: The current TNM classification that simply classifies differentiated thyroid carcinoma (DTC) patients younger than 55 years into stage I and stage II based on the presence or absence of distant metastases has been questioned. In this study, we reexamined the impact of T status and N status on prognosis and then developed a new prediction model to improve the predictability of cancer-specific survival (CSS) in young patients. MATERIALS AND METHODS: Kaplan–Meier method was applied to calculate the CSS. Multivariable Cox proportional hazards models were used to assess the impact of T status and N status on CSS after adjustment for known covariates. The area under the receiver operating characteristic curve (AUC), C-index, Bayesian information criterion (BIC), and Akaike information criterion (AIC) were calculated to compare model performance. RESULTS: A total of 9,242 DTC patients younger than 55 years were enrolled in the study. After adjusting for gender, age at diagnosis, race, pathology subtype, N stage, and M stage, T3 disease [hazard ratio (HR): 3.78, P = 0.006] and T4 disease (HR: 7.96, P < 0.001) remain independent predictors of CSS. Similarly, the 10-year CSS rate of N1b disease (HR: 3.78, P < 0.001) was significantly higher than that of N0 disease after adjustment. Moreover, Kaplan–Meier survival analysis showed that the 10-year CSS of stage II disease in younger patients with DTC showed a sharp decrease compared with that in older patients with DTC (74.47% vs. 98.43%, P < 0.001). Furthermore, a modified TNM staging system based on significantly prognostic T stage and N stage was established, which showed better performance than the current TNM staging system (P < 0.05). The new prediction model is also applicable to papillary thyroid carcinoma patients and follicular thyroid carcinoma patients. CONCLUSIONS: This is the first study to question the rationality of the current TNM staging system for patients younger than 55 years and successfully develop a new prognostic model, which improves prognostic stratification and guides individualized management.