Predictive Value of Plasma Epstein-Barr Virus DNA Concentration for Recurrence and Metastasis in Advanced-Stage Nasopharyngeal Carcinoma: A Longitudinal, Descriptive Investigation.

Background: Vietnam is an endemic region for nasopharyngeal cancer (NPC), with approximately 70% of cases diagnosed at stage III-IVa and 90% presenting with undifferentiated histology closely related to Epstein-Barr virus (EBV) infection. However, no studies have identified biomarkers predictive of recurrence and metastasis. This study aimed to determine the cut-off concentrations of cell-free (cf) EBV DNA for predicting recurrence and metastasis in NPC. Methods: A longitudinal descriptive study was conducted on 58 patients with stage III-IVa undifferentiated NPC between August 2021 and August 2024. We analysed the predictive value of cf EBV DNA concentrations at pre-treatment (preEBV) and post-treatment (postEBV, 6 months postEBV [EBV6], 12 months postEBV [EBV12]) in relation to disease progression and survival outcomes. Results: Of the 58 patients, 23 experienced recurrence and/or metastasis. The recurrence prediction cut-off concentration was 3980.0 copies/mL for preEBV (area under the curve [AUC] = 0.705, 95% confidence interval [CI]: 0.499-0.911, Se = 80.0%, Sp = 64.6%, odds ratio [OR] = 7.294, 95% CI: 1.389-38.307, accuracy [ACC] = 67.2%); 12.5 copies/mL for EBV6 (AUC = 0.783, 95% CI: 0.600-0.966, Se = 77.8%, Sp = 75.0%, OR = 10.5, 95% CI: 1.839-54.242, ACC = 75.5%); and 5.5 copies/mL for EBV12 (AUC = 0.766, 95% CI: 0.577-0.954, Se = 83.3%, Sp = 78.0%, OR = 17.778, 95% CI: 1.835-172.219, ACC = 78.7%). The metastasis prediction cut-off concentration for EBV12 was 42.5 copies/mL (AUC = 0.748, 95% CI: 0.502-0.994, Se = 66.7%, Sp = 80.5%, OR = 8.250, 95% CI: 1.278-52.254, ACC = 78.7%). Cut-off concentrations of preEBV, EBV6, and EBV12 were independent predictors of survival outcomes (except for EBV6). All results were statistically significant (P < .05). Conclusions: In advanced-stage NPC-undifferentiated subtype, preEBV, EBV6, and EBV12 serve as predictive biomarkers for recurrence and metastasis. Among these, EBV12 demonstrated the highest predictive value.