18F-FDG PET/CT Metabolic Characteristics of Nasopharyngeal Carcinoma Across AJCC/UICC TNM-8 and TNM-9 Staging Systems: A Retrospective Cross-Sectional Study.

BACKGROUND: The 9th edition of the AJCC/UICC TNM staging system (TNM-9) has introduced key updates for nasopharyngeal carcinoma (NPC) compared with TNM-8. However, there is limited data on the metabolic basis and performance of TNM-9 evaluated using 18F-FDG PET/CT. We aimed to investigate the association between PET/CT metabolic parameters and TNM-8 and TNM-9 staging systems, and evaluate the metabolic homogeneity across TNM-9 substages. METHODS: This single-center, retrospective cross-sectional study enrolled 822 NPC patients who underwent pre-treatment 18F-FDG PET/CT. Uptake, volumetric, glucose-normalized, and body composition-normalized metabolic parameters of the primary tumor (T) and the most metabolically active lymph node (LN) were compared across the TNM-8 and TNM-9 staging systems, and comparisons were also performed between the substages in the TNM-9 system. Multicollinearity diagnosis using the Variance Inflation Factor (VIF) and ordinal logistic regression were performed to identify independent stage-related parameters. RESULTS: Baseline age, fasting blood glucose and 18F-FDG dose were comparable across stages (all P>0.05), while weight differed significantly in both staging systems (both P<0.001). All metabolic parameters differed significantly among stages in both systems (all P<0.001). TNM-9 showed more coherent metabolic distributions compared with TNM-8, whereas TNM-8 exhibited distinct metabolic overlap between certain stages. Metabolic homogeneity was observed in volumetric parameters between TNM-9 stage Ia and Ib, and in all parameters between stage IVa and IVb. T/LN metabolic tumor volume (TMTV/LNMTV) and T/LN lean body mass-normalized maximum standardized uptake value (TSULmax/LNSULmax) were independent predictors in both systems, with a slightly higher McFadden R2 for TNM-9 (0.16 vs. 0.13). CONCLUSIONS: PET/CT metabolic parameters provide supportive evidence for the biological basis and clinical utility of TNM-9 in NPC. TNM-9 demonstrated superior metabolic homogeneity and slightly better model fit compared with TNM-8. TMTV, TSULmax, LNMTV, and LNSULmax can serve as promising complementary biomarkers for NPC staging.