Systemic Immune-Inflammatory Biomarkers in Epithelial Ovarian Cancer: Subgroup-Dependent Prognostic Performance and Integrated Risk Stratification.

Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are surrogate markers of the systemic immune-inflammatory response proposed as perioperative prognostic biomarkers in epithelial ovarian cancer (EOC), yet their performance across subgroups remains unexamined. In 373 EOC patients undergoing primary cytoreductive surgery, postoperative day-1 changes (ΔSII, ΔNLR, ΔPLR) were compared for overall survival (OS) and progression-free survival (PFS) across 10 subgroups, and a Clinical-Inflammatory Risk Score (CIRS) combining inflammation with stage and residual disease was developed. Individual markers showed modest discrimination (area under the curve [AUC] 0.579-0.615); the marker with the highest AUC varied by context, with ΔPLR ranking first most often, notably in non-serous tumors, though none was statistically superior. Seeking a molecular counterpart, two public transcriptomic cohorts were re-analyzed: VWF was consistently higher in clear cell than serous carcinoma, whereas IL6-STAT3-related differences were cohort-dependent. The CIRS achieved AUCs of 0.752 (OS) and 0.764 (PFS), a six-fold mortality gradient (7.2% vs. 44.4%), and remained independently associated with OS and PFS (hazard ratio 2.55 and 2.24 per standard deviation), though discrimination was not significantly better than stage and residual disease alone. These biomarkers show subgroup-dependent prognostic value, and the CIRS provides an exploratory risk-stratification framework warranting prospective validation.