Circulating IL-6 and survival outcomes in renal cell carcinoma: a systematic review and meta-analysis

INTRODUCTION & OBJECTIVES: Renal cell carcinoma (RCC) represents the majority of kidney malignancies and is characterized by variable outcomes, even with current systemic therapies. Interleukin-6 (IL-6), a proinflammatory cytokine implicated in tumor progression and immune suppression, has been proposed as a prognostic biomarker in RCC. However, the evidence remains inconsistent due to methodological heterogeneity across studies. Therefore, our study aims to evaluate the prognostic significance of IL-6 in RCC by synthesizing data from published studies, specifically overall survival (OS) and progression-free survival (PFS). METHODS: A systematic meta-analysis was conducted to evaluate the prognostic significance of IL-6 in RCC. Eligible studies were identified through PubMed, ScienceDirect, and ProQuest up to March 2025. Inclusion criteria encompassed original articles measuring pre-treatment serum IL-6 levels in RCC patients and reporting associations with overall survival (OS) or progression-free survival (PFS). Random-effects models were used to compute pooled hazard ratios (HRs) and survival differences. RESULTS: Nine studies comprising 702 RCC patients were included. Patients with low IL-6 levels had significantly longer OS (difference: 5.36 months; 95% CI: 2.2-8.53; p<0.001; I² = 0%) and PFS (difference: 6.41 months; 95% CI: 1.3-11.53; p=0.01; I² = 48.5%) compared to those with high IL-6. The pooled HR for survival associated with elevated IL-6 was 2.06 (95% CI: -0.23-4.36), with considerable heterogeneity (I² = 89.19%) and borderline statistical significance (p=0.08). Despite variations in study design, sample size, and IL-6 detection methods, elevated IL-6 consistently predicted worse clinical outcomes. CONCLUSIONS: IL-6 is a promising prognostic biomarker in RCC, with elevated levels associated with significantly poorer OS and PFS.