Endothelial activation and stress index as a prognostic marker in metastatic renal cell carcinoma

Background/objectives The Endothelial Activation and Stress Index (EASIX) is a simple biomarker calculated using LDH, serum creatinine, and platelet count and has shown prognostic significance in various malignancies. However, data on its prognostic role in metastatic renal cell carcinoma (mRCC) are limited. This study investigated the prognostic significance of EASIX in mRCC and compared it with conventional systemic inflammatory indices. Methods This retrospective study included 143 patients with mRCC between January 2016 and December 2025. EASIX was calculated using baseline lactate dehydrogenase (LDH), serum creatinine, and platelet count. Exploratory ROC analyses based on observed mortality status were performed to evaluate the discriminatory ability of EASIX, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), and to determine a cohort-derived EASIX cut-off value. Overall survival (OS) was assessed using the Kaplan–Meier method and Cox regression analyses were performed to identify factors associated with OS. Additional sensitivity analyses adjusting for ECOG performance status and clinical factors were performed in patients with available ECOG data. Results Exploratory ROC analysis of observed mortality identified an EASIX cut-off of 1.293 (AUC: 0.855; 95% CI: 0.796–0.915; p < 0.001), with 82.4% sensitivity and 69.6% specificity. ROC analyses of NLR, MLR, PLR, and SII were not statistically significant. Median OS was 22.0 months (95% CI: 14.8–29.2) in the high EASIX group (>1.293) and was not reached in the low EASIX group (≤1.293; log-rank p < 0.001). High EASIX remained associated with increased mortality after multivariable adjustment (HR: 4.031; 95% CI: 2.146–7.572; p < 0.001) and in ECOG-adjusted sensitivity analysis (HR: 4.149; 95% CI: 1.989–8.653; p < 0.001). Liver metastasis (HR: 2.054; 95% CI: 1.152–3.663; p = 0.015) and lung metastasis (HR: 1.618; 95% CI: 1.015–2.580; p = 0.043) were also associated with worse OS. Conclusions High EASIX was associated with worse overall survival in patients with mRCC and demonstrated significant discriminatory ability for observed mortality in exploratory ROC analysis. EASIX may serve as a simple and readily available biomarker for prognostic assessment in mRCC, although the cohort-derived cut-off value requires validation in independent patient populations.