Prognostic Value of Histological Subtypes and Clinical Factors in Non-Endemic Nasopharyngeal Carcinoma: A Retrospective Cohort Study

<i>Background and Objectives</i>: Nasopharyngeal carcinoma (NPC) displays marked geographic and histopathological heterogeneity, and prognostic determinants in non-endemic regions remain incompletely defined. This study aimed to evaluate the impact of clinicopathological characteristics and treatment modalities on survival outcomes among patients with stage II-IVA NPC treated with curative intent at a single tertiary cancer center. <i>Materials and Methods</i>: A retrospective analysis was conducted on 81 consecutive patients with histologically confirmed NPC treated between 2000 and 2022. Demographic, clinical, and treatment parameters were extracted from institutional records. Survival outcomes-including disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS)-were estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic variables identified in univariate analysis were further assessed by multivariable Cox proportional hazards regression (Cox's model). <i>Results</i>: The cohort included 59 men (72.8%) and 22 women (27.2%), with a median age of 50.8 years (range, 19-78). Most patients presented with locally advanced disease (T3-T4, 53.1%; N2, 60.5%; stage III-IVA, 87.7%). Non-keratinizing undifferentiated carcinoma (World Health Organization [WHO] type III) was the predominant histology (71.6%), followed by the non-keratinizing differentiated subtype (17.3%). Median DFS and OS were 94.6 and 139.4 months, respectively. According to the univariate analysis, histological subtypes and a family history of cancer were significantly associated with DFS, whereas comorbid systemic disease showed an unexpected association with longer DMFS. The multivariable Cox model identified the histological subtype as an independent predictor of disease recurrence (HR = 2.23, 95% CI: 1.00-4.94; <i>p</i> = 0.049). For OS, both histological subtype (HR = 2.40, 95% CI: 1.10-5.25; <i>p</i> = 0.029) and age at diagnosis (HR = 1.05, 95% CI: 1.02-1.09; <i>p</i> = 0.005) were independent adverse prognostic factors. <i>Conclusions</i>: In this long-term, single-center study from a non-endemic region, histological subtype emerged as the most powerful determinant of prognosis, significantly influencing both DFS and OS. Patients with non-keratinizing undifferentiated (WHO type III) carcinoma demonstrated superior outcomes compared with those with differentiated histology. Additionally, increasing age at diagnosis was independently associated with poorer OS. In contrast, inflammatory and nutritional biomarkers, the Pan-Immune-Inflammation Value (PIV) and the Prognostic Nutritional Index (PNI), showed no prognostic significance. These findings underscore the continued prognostic relevance of histopathologic classification and age and highlight the need for large-scale, standardized studies integrating Epstein-Barr virus (EBV) status and host-related factors in non-endemic NPC populations.