The Clinical Value of Plasma Epstein-Barr Virus DNA as a Tumor Marker in Nasopharyngeal Carcinoma: Prognostic? Yes, But How Can We Best Use It?

Abstract

N asopharyngeal carcinoma (NPC) is a rare cancer overall, accounting for only 0.7% of cancers diagnosed worldwide. 1 It is, however, relatively common in Southeast Asian countries, and in endemic regions of China, it reaches an incidence of around 20/100,000. 2 Epstein-Barr Virus (EBV) infection is an etiologic factor in the development of endemic, nonkeratinizing (World Health Organization type II/III) NPC, 3 and plasma EBV-DNA levels at different time points in treatment have been correlated with prognostic endpoints, including distant metastasis, locoregional recurrence, and death. [4][5][6][7][8][9][10][11][12][13][14] Prognostic models using EBV-DNA levels have been devised to supplement TNM staging, and EBV-DNA levels are used in some institutions to monitor disease recurrence during posttreatment surveillance. 4,15 The role of EBV-DNA in NPC is an area of extensive research, with scores, if not hundreds, of publications on the subject in the last 20 years.In the current issue of The Cancer Journal, He and colleagues report on the prognostic value of EBV-DNA levels before, after, and in long-term follow-up after treatment for NPC. This retrospective review is one of the larger series of patients in the EBV-DNA/NPC literature and provides some intriguing data on the kinetics of EBV-DNA posttreatment. Consistent with previous studies, the authors found that higher pretreatment and posttreatment EBV-DNA load were each correlated with poorer overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival. The authors used receiver operating characteristic analysis to identify cutoff values for EBV-DNA load before treatment and after treatment that correlated with outcomes. Patients with EBV-DNA load above the cutoff values both before and after treatment-the "continuously elevated" group-had substantially worse 5-year OS and DMFS (59.9% for each endpoint) than patients whose EBV-DNA load exceeded neither the pretreatment nor posttreatment cutoff values ("continuously normal" group; 5-year OS 93.2% and DMFS 94.4%) and those who had EBV-DNA load above cutoff at any time point ("ever-elevated" group; 5-year OS 76.2% and DMFS 84.3%). In addition, the authors report consistent patterns of dynamic changes in EBV-DNA levels seen in the posttreatment follow-up period and suggest that further study may allow us to take advantage of these patterns to earlier detect the development of recurrent or metastatic disease. It is worth noting that no patients in this cohort received adjuvant chemotherapy.The findings presented by He and colleagues offer further evidence of the prognostic value of EBV-DNA levels in NPC, but it remains unclear how EBV-DNA load can be used to inform the management of these patients. The authors seem to be most focused on using this as a biomarker to aid in early detection of recurrent/metastatic disease. If rising EBV-DNA levels foreshadow the development of distant metastatic disease, and this allows earlier initiation of systemic therapy, there are gains to be made i...