C-reactive protein and the neutrophil-to-lymphocyte ratio are prognostic biomarkers in metastatic renal cell carcinoma patients treated with nivolumab

  • Kotaro Suzuki
  • Tomoaki TerakawaEmail author
  • Junya Furukawa
  • Kenichi Harada
  • Nobuyuki Hinata
  • Yuzo Nakano
  • Masato Fujisawa
Original Article



Association between systemic inflammation and clinical outcome of immune checkpoint inhibitors (ICIs) has received focus. Our objective was to evaluate the utility of the neutrophil-to-lymphocyte ratio (NLR) in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab as well as the prognostic impact of the C-reactive protein (CRP) level.

Materials and methods

Sixty-five mRCC patients treated with nivolumab were enrolled. We retrospectively investigated several factors, including the NLR and the CRP level, for their association with progression-free survival (PFS) and overall survival (OS). In addition, we evaluated their impact on the objective response.


The CRP level was confirmed to be positively correlated with the NLR in a correlation analysis. An NLR ≥ 5 was significantly associated with a worse PFS (hazard ratio [HR]: 4.54, 95% confidence interval [CI] 1.93–10.7; p < 0.001), and an NLR ≥ 5 and a CRP ≥ 2.1 mg/dL were identified as a significant factors predicting worse OS with HRs of 4.88 (95% CI 1.35–17.7; p < 0.016) and 3.89 (95% CI 1.01–15.0; p = 0.049), respectively. In addition, patients with a ≥ 25% decrease in the NLR and CRP level showed a significantly better response to nivolumab than those without a ≥ 25% decrease in the NLR and CRP level, with odds ratios of 9.54 (95% CI 2.09–49.8, p = 0.001) and 4.36 (95% CI 1.03–18.9, p = 0.032), respectively.


Both the NLR and CRP levels were significantly associated with the clinical outcome of nivolumab in mRCC patients. The potential prognostic impact of those markers needs to be further prospectively investigated.


Metastatic renal cell carcinoma (mRCC) Nivolumab Immune checkpoint inhibitor (ICI) Neutrophil-to-lymphocyte ratio (NLR) C-reactive protein (CRP) Overall survival (OS) 



Adverse event


Confidence interval


C-reactive protein


Anti-cytotoxic T-lymphocyte antigen-4


Hazard ratio


Immune checkpoint inhibitor


International metastatic renal cell carcinoma Database Consortium


Immune-related adverse event


Karnofsky performance status


Metastatic renal cell carcinoma


Neutrophil-to-lymphocyte ratio


Objective response rate


Overall survival


Anti-programmed death-1


Progression-free survival


Anti-programmed death-ligand 1


Multitargeted receptor tyrosine kinase inhibitor


Author contributions

KS, TT and KH designed the study. KS, TT, JF, KH acquired and analyzed the data. KS, TT and KH drafted the manuscript, and JF, NH, YN and MF revised it critically for important intellectual content. All authors gave final approval of the version to be published.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study design was approved by the Research Ethics Committee of our institution (No. B190059), which was conducted in accordance with the Declaration of Helsinki. Informed consent to participate in the present study was obtained from all patients.


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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  1. 1.Division of UrologyKobe University Graduate School of MedicineKobeJapan

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