AbstractWe aim to evaluate the quantitative parameters of ¹⁸F-FDG PET/CT (metabolic parameters) and MRI (morphologic parameters) for prognostication and risk stratification in nasopharyngeal carcinoma (NPC). 200 (147 males, aged 50 ± 13 years-old, mean ± S.D.) newly diagnosed patients with NPC (T_xN_xM₀) were prospectively recruited. Primary tumor and nodal lesions were identified and segmented for both morphologic (volume, VOL) and metabolic (SUV and MTV) quantification. Independent predictive factors for recurrence free survival (RFS) and overall survival (OS) were morphologic nodal volume (VOL_N, p < 0.001), TNM-stage (p = 0.022), N-Stage (p = 0.024) for RFS, and VOL_N (p = 0.014) for OS. Using Classification and Regression Tree (CART) analysis, three risk-layers were identified for RFS: Stage I/II with VOL_N < 18cc (HR = 1), stage III /IV with VOL_N < 18cc (HR = 2.93), VOL_N ≥ 18cc (HR = 7.84) regardless of disease stage (p < 0.001). For OS, two risk layers were identified: VOL_N < 18cc (HR = 1), VOL_N ≥ 18cc (HR = 4.23) (p = 0.001). The 18cc threshold for morphologic nodal volume was validated by an independent cohort (n = 105). Based on the above risk-classification, 35 patients (17.5%) would have a higher risk than suggested by the TNM-staging system. Thus, morphologic nodal volume is an important factor in prognostication and risk stratification in NPC, and should be incorporated into the staging system, while PET parameters have no advantage for this purpose in our cohort.