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

Urol Oncol. 2021 Apr;39(4):239.e17-239.e25. doi: 10.1016/j.urolonc.2020.12.020. Epub 2021 Jan 21.

Abstract

Objective: To evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.

Patients and methods: We retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models.

Results: We included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7-28) and 4 months (interquartile range 3-11), respectively. Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16-1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08-1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS. Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04-1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01-1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS.

Conclusions: Elevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.

Keywords: C-reactive protein; Immune checkpoint inhibitor; Metastatic clear-cell renal cell carcinoma; Neutrophil-lymphocyte ratio; Nivolumab.

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • C-Reactive Protein / analysis*
  • Carcinoma, Renal Cell / blood*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Female
  • Humans
  • Kidney Neoplasms / blood*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Leukocyte Count
  • Lymphocytes*
  • Male
  • Middle Aged
  • Neutrophils*
  • Nivolumab / therapeutic use*
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents, Immunological
  • Nivolumab
  • C-Reactive Protein

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma