Enhanced prognostic stratification in early-stage epithelial ovarian cancer: multi-histological analysis of neutrophil-to-lymphocyte ratio with particular emphasis on clear cell histology

In Asian populations, early-stage ovarian cancers account for approximately half of cases, substantially exceeding proportions observed in Western cohorts, with clear cell carcinoma (CCC) and endometrioid carcinoma (EMC) demonstrating markedly higher prevalence in Asian women. The tumor immune microenvironment critically influences oncological progression, and systemic inflammatory biomarkers can serve as surrogates of host immunological responses. This study evaluated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), an established index of systemic inflammation and immune dysregulation, across histologic subtypes in early-stage epithelial ovarian cancer. We retrospectively analyzed patients with FIGO stage I-II epithelial ovarian cancer diagnosed between 2011 and 2018. Pretreatment NLR was calculated to reflect the balance between neutrophil-driven inflammation and lymphocyte-mediated immunity. Among 217 enrolled patients, CCC (28.1%) and EMC (34.6%) constituted the predominant histotypes, consistent with Asian demographic patterns. In univariable analyses, elevated NLR and advanced stage significantly correlated with diminished progression-free survival (HR 5.04, P<0.001; HR 3.81, P<0.001) and overall survival (HR 4.54, P=0.013; HR 3.91, P=0.003). In multivariable models, NLR remained an independent prognostic factor for both endpoints (PFS: HR 5.38, P=0.001; OS: HR 4.27, P=0.048). Histology-stratified analyses revealed distinctive immunological signatures, with elevated NLR in CCC patients exhibiting exceptionally strong prognostic value (univariable PFS: HR 8.14, P=0.001; OS: HR 22.42, P=0.005; multivariable PFS: HR 8.00, P=0.007; OS: HR 32.43, P=0.025), providing information beyond FIGO stage. Conversely, NLR demonstrated no prognostic relevance in EMC patients, indicating heterogeneous immune microenvironments across histological variants. Elevated pre-treatment NLR independently predicts adverse outcomes in early-stage epithelial ovarian cancer, with particularly pronounced prognostic utility in CCC. These findings may be especially relevant in Asian populations, in which CCC is more common, and could inform personalized risk stratification.