Clinical features and outcomes of EBER-negative nasopharyngeal carcinoma: A large cohort study across China.

e18144 Background: The current TNM staging system and treatment guidelines are primarily based on EBER-positive nasopharyngeal carcinoma (NPC) patients, leaving a lack of high-level evidence to guide treatment decisions for EBER-negative patients. This study aims to clarify its clinical features and inform future therapeutic strategies. Methods: We conducted a multicenter study across seven centers in China. Key inclusion criterion required NPC patients to have undergone EBER in situ hybridization. The Kaplan-Meier curves were used for survival analysis, and inter-group differences were compared using the log-rank test. Multivariable Cox proportional hazards models evaluated the impact of clinical and pathological factors on survival outcomes. Propensity score matching (PSM) was performed at a 1:4 ratio between EBER-negative and EBER-positive cohorts, with matching based on clinical characteristics. A prognostic risk stratification model was performed. Results: This study analyzed 248 (20%) EBER-negative and 992 (80%) EBER-positive patients. Among these, 876 were male (71%). The EBER-negative NPC was significantly associated with the keratinizing subtype (26.2% vs. 0.7%, P < 0.001). Cox multivariable regression analysis of 1,240 patients identified EBER as an independent prognostic factor for NPC (HR = 0.49, 95% CI = 0.35-0.70, P < 0.0001). Compared to EBER-positive patients, EBER-negative NPC had significantly inferior 5-year overall survival (79.9% vs. 90.2%), progression-free survival (PFS, 67.6% vs. 77.3%), and locoregional recurrence-free survival (84.3% vs. 92.1%, all P < 0.001). Conversely, EBER-negative patients exhibited a lower risk of distant metastasis, with a lower 5-year distant metastasis-free survival rate (92.3% vs. 86.0%, P = 0.006). Multivariate analysis shows T stage (HR = 1.45, 95% CI = 1.05–1.99, P = 0.02) and hypertension status (HR = 1.68, 95% CI = 1.03–2.75, P = 0.04) as independent prognostic factors for PFS in the EBER-negative cohort. The combined model, which included T stage, hypertension status, and others, had a higher discriminative performance for PFS (AUC, 0.741) compared to hypertension status, T stage alone, or other combination models (0.54, 0.58 and,0.62, respectively). Based on these factors, patients were divided into three risk groups, with 5-year PFS rates of 80.1%, 64.3%, and 52.5%, respectively (p=0.0011). Conclusions: EBER-negative NPC is a distinct, aggressive subtype characterized by keratinizing histology and poorer overall survival, yet it is associated with a lower risk of distant metastasis compared to EBER-positive NPC. A practical risk-stratification model was built. Further studies are needed to confirm these findings and explore potential clinical applications.