Refining M1-Stage Stratification in De Novo Metastatic Nasopharyngeal Carcinoma Using 18F-FDG PET/CT

Purpose: To validate the American Joint Committee on Cancer (AJCC) 9th edition M1-stage subdivision for de novo metastatic nasopharyngeal carcinoma (DM-NPC) and explore preliminary evidence for a refined classification using 18F-FDG positron emission tomography/computed tomography (PET/CT)-derived metastatic burden. Patients and Methods: A retrospective cohort of 185 DM-NPC patients diagnosed between 2000 and 2022, who underwent pretreatment 18F-FDG PET/CT, was analyzed. Recursive partitioning analysis (RPA) identified prognostic cutoffs for metastatic lesions. Survival outcomes were compared between AJCC 9th edition M1 subgroups (M1a: ≤3 lesions; M1b: >3 lesions) and a redefined PET-based classification (Rd-M1a: single-organ, ≤4 lesions; Rd-M1b: >5 lesions or multiorgan). Results: Patients with single-organ metastases and ≤4 lesions showed potentially superior overall survival (OS) (2-y OS: 60.4% vs. 29.0%; 3-y OS: 46.2% vs. 19.6%; P <0.001). Higher metastatic burden (>5 lesions) was independently associated with worse OS (HR: 1.81; 95% CI: 1.24–2.64; P =0.002). The redefined classification suggested better prognostic discrimination than the AJCC 9th edition (C-index: 0.594 vs. 0.562; AUC at 36 mo: 0.649 vs. 0.598). Patients classified as Rd-M1b had a significantly unfavorable OS compared with those in the Rd-M1a group (HR: 2.02, 95% CI: 1.39–2.92; P =0.002). Conclusions: These preliminary findings suggest that 18F-FDG PET/CT may enhance M1-stage stratification by quantifying metastatic burden and distribution in patients with DM-NPC, potentially offering improved prognostic accuracy. However, as a single-institution retrospective study, external validation is essential to confirm these observations and guide personalized treatment strategies.