3506 - Validation and Development of N Category for Nasopharyngeal Carcinoma Based on the Ninth Version of AJCC/UICC TNM Staging System in Non-High-Incidence Regions of China: A Multicenter Cohort Study

Purpose/Objective(s): The 9th edition of the AJCC/UICC staging system for nasopharyngeal carcinoma (NPC) incorporates advanced extranodal extension (ENE) into the N3 classification for the first time. Our study aims to validate the applicability of the 9th edition N classification in non-high-incidence regions and to evaluate the justification for incorporating advanced ENE into the N3 category, along with its potential clinical implications under different treatment strategies.

Materials/Methods: We retrospectively collected clinical and imaging data of NPC patients diagnosed between 2011 and 2021 from three cancer centers in Jiangsu, Zhejiang, and Anhui Provinces, who were aged 18–75 years, had complete follow-up and MRI, and received radiotherapy-based treatment. The primary endpoints were OS, PFS, DMFS, and LRFS. Survival outcomes were analyzed by Kaplan–Meier method and Cox proportional hazards model, while model discrimination were evaluated by Harrell’s C-index (with 1000 bootstrap resamples) and Akaike information criterion (AIC).

Results: A total of 1,355 patients were included in this study, with a median age of 50 years (IQR: 43–57); 71.8% were male and 28.2% were female. According to the new staging system, 136 patients who were originally classified as N1/N2 but exhibited advanced ENE were reclassified as N3, increasing the total number of N3 cases to 218. Kaplan–Meier analysis showed that, in terms of all endpoints, the survival curves of N3 were more distinctly separated from N0–N2 under the 9th edition, with significant intergroup differences (p < 0.005), indicating improved identification of high-risk patients. Across the overall, internal, and external validation cohorts, the 9th edition yielded significantly higher C-index values for OS and PFS compared with the 8th edition, along with consistently lower AIC values, indicating better model fit and discriminative ability in survival prediction. Further analysis revealed that within the 9th edition N3 group, patients with advanced ENE exhibited significantly poorer OS, PFS, and DMFS compared with their counterparts. Multivariable Cox regression analysis identified advanced ENE as an independent adverse prognostic factor for OS (HR = 1.78, p = 0.032) and DMFS (HR = 2.05, p = 0.008). In addition, patients with T4 showed significantly higher risks of all survival outcomes, and targeted therapy was significantly associated with improved OS (HR = 0.49, p = 0.015).

Conclusion: The 9th edition AJCC/UICC N classification system showed superior prognostic discrimination over the 8th edition in nasopharyngeal carcinoma patients from non-endemic regions. Incorporating advanced ENE into the N3 category enhanced high-risk patient identification, supporting the applicability of the new system and informing optimization of treatment strategies.