Refinement of N category in version-nine of AJCC/UICC TNM staging system for nasopharyngeal carcinoma based on the international consensus recommendations for diagnosing extranodal extension.
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OBJECTIVES: To ascertain the prognostic value of grade 2 imaging extranodal extension (G2 iENE), also called matted nodes (MNs), in nasopharyngeal carcinoma (NPC) based on the 9th-version of AJCC/UICC TNM staging system (TNM-9) and the Head and Neck Cancer International Group (HNCIG)'s criteria for diagnosing iENE, and propose future refinement of the TNM-9 N category. MATERIALS AND METHODS: Non-metastatic NPC patients treated between 2017 and 2018 were screened. MRI data were reviewed for re-staging according to the TNM-9 and iENE status per the HNCIG-criteria. Five-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) were analyzed. Recursive partitioning analysis (RPA) based on the ordinal N category of TNM-9 and the G2 iENE status were performed to propose a refined N category. RESULTS: Totally, 1334 patients were included, with 462 (34.6%) patients presenting with G2 iENE at baseline. Besides N Category, G2 iENE also showed independent prognostic value for OS (HR: 1.453, P = 0.042), PFS (HR: 1.293, P = 0.057) and DMFS (HR: 1.363, P = 0.042). The RPA-N category was then derived: RPA-N0 (N0), RPA-N1 (N1 without G2 iENE), RPA-N2 (N1 with G2 iENE and N2) and RPA-N3 (N3). The RPA-N classification had a lower Akaike information criterion (AIC) and higher C-index for all endpoints, and performed better in hazard consistency, hazard discrimination, sample size balance and outcome prediction when compared to TNM-9. CONCLUSIONS: G2 iENE, based on the HNCIG-criteria, constitute an independent adverse prognostic factor for NPC based on the TNM-9. The RPA-N category, which integrated N category of TNM-9 and G2 iENE, demonstrated better performance than N category in TNM-9, further validation in multicenter cohorts is warranted.