The prognostic impact of systemic inflammation and nutritional indicators on targeted therapy for renal cell carcinoma: A systematic review and meta-analysis

Yushuang Xiao^1,2Yang Dai^1,3,4Xushu Zhong^1,3,4Luocheng Zhang^1,2Ruilian Xie^1,2Qiaolin Zhou^1,2Wenyi Liang^1,2Xu Sun^1,2Mengting Yang^1,2Zhuohang Zou^1,2Yutong Wang^1,2He Li^1,3,4*Ting Niu^1,3,4*

• ¹Sichuan University West China Hospital Department of Hematology, Chengdu, China
• ²West China Medical School, West China Hospital, Sichuan University, Chengdu, China
• ³West China Hospital of Sichuan University State Key Laboratory of Biotherapy, Chengdu, China
• ⁴National Facility for Translational Medicine (Sichuan), West China Hospital, Sichuan University, Sichuan, China

Introduction: The prognosis of metastatic renal cell carcinoma (mRCC) varies significantly, and early treatment failure is common. Systemic inflammation and nutritional indicators may predict the survival outcomes of patients with renal cell carcinoma (RCC) receiving targeted therapy. However, an integrated evaluation of the prognostic value of these markers is still lacking. This study aims to comprehensively assess and compare the prognostic significance of various systemic inflammation and nutritional indicators for the overall survival (OS) and progression-free survival (PFS) of patients with RCC undergoing targeted therapy through systematic review and meta-analysis. Methods: According to PRISMA guidelines, a systematic search was performed across PubMed, Embase, Cochrane Library, Web of Science, Scopus, Medline up to October 17, 2025. Retrospective cohort studies evaluating the correlation between baseline inflammatory/nutritional indicators and OS/PFS in RCC patients receiving targeted therapy were included. And biomarkers included Neutrophil-to-Lymphocyte Ratio (NLR), C-Reactive Protein (CRP), Platelet-to-Lymphocyte Ratio (PLR), Body Mass Index (BMI), Albumin (Alb), Prognostic Nutritional Index (PNI), Systemic Immune-Inflammation Index(SII), Neutrophil Count (NEU), and hemoglobin (Hb). Two researchers independently performed literature screening, data extraction, and quality assessment. Meta-analysis was performed using Stata 18.0. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated. And heterogeneity tests, sensitivity analyses, subgroup analyses, and publication bias assessments were conducted. This analysis has been registered in PROSPERO (CRD420251167462). Results: A total of 152 retrospective cohort studies involving 33,842 patients were included. The meta-analysis revealed that high baseline NLR, NEU, SII, and low Hb levels were significantly associated with poorer OS. The combined HR values were as follows: NLR for OS: HR = 1.82, 95%CI = 1.67-1.99; NEU for OS: HR = 1.88, 95%CI = 1.67-2.12; SII for OS: HR = 1.92, 95%CI = 1.72-2.15; Hb for OS: HR = 1.74, 95%CI = 1.58-1.92. Additionally, NLR (HR = 1.51, 95%CI = 1.38-1.65) was also significantly associated with poorer PFS. Discussion: NLR, NEU, SII and Hb are robust and consistent prognostic predictors for patients with RCC receiving targeted therapy. The evidence all stems from retrospective observational studies therefore selection bias and the influence of unmeasured confounding factors could not be fully controlled for.