Validation of the 8th Edition of AJCC/UICC Staging System for Nasopharyngeal Carcinoma in the Non-Endemic Area and Proposing a New N-Staging System

Abstract

Prompt validation of new staging system is crucial for cancer management. Since the publication of the 8th edition of AJCC staging system, few validated studies were published. Till now, it lacks evidence from non-endemic area of China and other area of the world. The aim of this study is to assess the applicability and extrapolation of the 8th edition of AJCC staging system for nasopharyngeal carcinoma (NPC) in non-endemic area. This retrospective study enrolled 781 patients from East China, with non-metastatic NPC treated by definitive IMRT. All patients were restaged according to the 7th and 8th edition of AJCC staging system. Univariate and multivariable models were constructed to evaluate the association between risk factors and survival. Based on the multivariate-analysis, recursive partitioning analysis (RPA) derived new N stages objectively. The performance of each staging system was compared using the Harrell’s concordance index (c-index). For T category, given the overlap of local recurrence-free survival (LRFS) curves across T1-3, both the 7th and 8th edition of T category did not show a good capacity of discriminations of LRFS. However, the separations of Distant metastasis-free survival (DMFS) between T4 to T2/T3 were better in the 8th edition. The 8th edition had a higher C-index than the 7th edition, in terms of DMFS and overall survival (OS). For N category, 4.9% of N1 upgraded to N3 and 19.5% of N2 upgraded to N3, based on the 8th edition. All of the upgraded cases were attributed to the involvement of level IVa and level Vb. Hence, significant stage migration decreased the disparities of N2 and N3 disease and the 8th edition had a lower C-index than 7th edition, in terms of DMFS, Disease-free survival (DFS) and OS. Total number of positive nodal levels (TNL) was an independently prognostic factor for DMFS and OS after adjusting for various risk factors. New N staging system using nodal size and TNL was derived from RPA. The proposed N staging system significantly improved the discriminations of DMFS, DFS and OS, compared with the 7th and the 8th edition (Table 1). Given the significant stage migration, the extrapolation of the 8th edition staging system in the non-endemic area is questioned.Total number of positive nodal levels is a prominent surrogate of metastatic nodal burden, which may be considered in the future refinement of staging system.Abstract 2903; Table 1The comparison of prognostic ability of the 7th , 8th, and the proposed overall stage system to discriminate survival rates.DFS (%)7th edition8th editionProposed editionOS (%)7th edition8th editionProposed editionI89.089.088.0I95.695.695.3II88.287.885.4II92.893.293.2III69.271.268.9III81.784.182.4IVA73.665.862.8IVA83.776.870.4IVB56.5IVB72.4c-index0.62560.62300.6339c-index0.63040.63860.6687p value0.0000.0000.000p value0.0000.0000.000 Open table in a new tab