Risk Stratification in T4 or N3 Nasopharyngeal Carcinoma

To investigate the prognostic heterogeneity among stage III nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system to identify potential subgroups requiring tailored therapeutic strategies. We retrospectively included stage III patients (T1-3N3 or T4N0-3) who were diagnosed with NPC between January 2015 and December 2021 according to the 9th edition of the AJCC/UICC staging system. Kaplan-Meier method and multivariable Cox regression analyses were used for statistical analysis. We included 309 patients in this study. A total of 92/309 (29.8%) patients developed locoregional recurrence and/or distant metastasis with a median follow-up of 52.9 months. Those with T4N3 disease had significantly lower distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) but comparable locoregional relapse-free survival (LRFS) to those with T1-3N3 and T4N0-2 disease. Those with T4N3 disease had comparable LRFS but had significantly lower 5-year DMFS (78.7% vs. 44.7%, p<0.001), PFS (65.7% vs. 27.6%, p<0.001), and OS (77.1% vs. 45.9%, p<0.001) compared to those with stage T4N0-2 and T1-3N3 diseases. Similar results were confirmed using the multivariate analysis. Our study demonstrates the prognostic heterogeneity of stage III disease within the 9th edition NPC staging system. T4N3 category should be considered separately and treated as a distinct entity regardless of the staging editions.