Reviews - Oncology
Vol. 97 No. 3 (2025)
https://doi.org/10.4081/aiua.2025.13955

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

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Received: 10 May 2025
Accepted: 5 June 2025
Published: 30 September 2025
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Renal cell carcinoma, interleukin-6, prognosis, survival, biomarker

Authors

Haryo Nindito Wicaksono
wicaksonoharyo123@gmail.com
https://orcid.org/0009-0009-8807-0321
Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia.
Taufiq Nur Budaya
https://orcid.org/0000-0001-8906-3144
Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia.
Kurnia Penta Seputra
Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia.
Aulia Rahman Putra
https://orcid.org/0000-0002-9112-3174
Department of Urology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia.

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.

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Circulating IL-6 and survival outcomes in renal cell carcinoma: a systematic review and meta-analysis. (2025). Archivio Italiano Di Urologia E Andrologia, 97(3). https://doi.org/10.4081/aiua.2025.13955
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