Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Abstract

There is increasing evidence to suggest that the neutrophil-to-lymphocyte ratio (NLR) is related to the prognosis of patients with renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs). However, these findings are inconsistent. The present study was performed with the aim of exploring the utility of NLR in patients with RCC treated with ICIs. For this purpose, a comprehensive search of PubMed, Web of Science, and Embase was performed to find studies evaluating the prognostic value of NLR. The overall survival (OS) and progression-free survival (PFS) were the assessed clinical outcomes. All statistical analysis was performed using Stata version 12.0 software. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) of NLR for OS and PFS were calculated using the random-effect models. Heterogeneity was evaluated based on the I2 value and Cochran’s Q test. Egger’s and Begg’s tests were applied to precisely assess the publication bias. The “trim and fill” method was adopted to perform the sensitivity analysis to determine whether the results were stable. In total, 12 studies encompassing 1,275 patients were included in the final analysis. The results revealed that a high NLR at baseline or pre-therapy was associated with a poor OS (HR, 2.23; 95% CI, 1.84–2.70; p < 0.001) and PFS (HR, 1.78; 95% CI, 1.72–2.09; p < 0.001). During the course of treatment, a decrease in the NLR was associated with a significantly longer OS (HR, 0.34; 95% CI, 0.20–0.56; p < 0.001) and PFS (HR, 0.44; 95% CI, 0.30–0.63; p < 0.001) compared to an increase in NLR. As a preliminary screening of other risk factors, age, sex, race, and IMDC risk may have a certain prognostic value for RCC treated with ICIs. People over 70 years old had better OS compared to people younger than 70 (HR, 0.65; 95% CI, 0.48–0.89). Non-Caucasians treated with immunotherapy had a worse OS (HR, 8.67; 95% CI, 2.87–26.2) and PFS (HR, 2.65; 95% CI, 1.28–5.48) than Caucasians. Males had a worse OS than females (HR, 1.48; 95% CI, 1.14–1.93). Compared with the IMDC favorable risk group, the OS of the IMDC poor risk group was worse (HR, 2.59; 95% CI, 1.56–4.32). There was no significant publication bias or heterogeneity observed in the present study. On the whole, the present study demonstrated that an elevated NLR is associated with an adverse OS and PFS in patients with RCC treated with ICIs. The NLR may thus be used as a readily available prognostic biomarker for these patients. Age, sex, race, and IMDC risk may have potential predictive value for the prognosis of RCC treated with ICIs. However, further investigations are warranted to validate these results.

A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy

“…The trial design allowed us to prospectively evaluate the effect of targeted therapy alone and in combination with ICT in the peripheral and intratumoral immune subpopulations. Baseline peripheral blood NLR was found to correlate with response to sitravatinib plus nivolumab combination therapy, similar to what has been observed with nivolumab monotherapy ( 17 , 18 ). Sitravatinib alone or in combination with nivolumab did not reduce peripheral blood NLR, which may explain why elevated baseline NLR was predictive of poor response to the combination regimen.…”

“…Baseline peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a clinically accessible biomarker of response to nivolumab monotherapy in patients with advanced ccRCC ( 17 , 18 ). We found that elevated baseline NLR was associated with lower ORR (posterior probability of 97.9%; table S11, Fig.…”

“…All analyses used NLR as a continuous variable. However, for presentation purposes in figures, we used a cutoff value of 3, because this is the most commonly used NLR cutoff value across RCC studies ( 18 ).…”

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

“…All previous meta-analyses about immunotherapy and NLR focused on the impact of baseline NLR on prognosis [ 60 , 61 , 62 , 63 , 64 , 65 ]. Although a small part of the meta-analyses included a few studies addressing the dynamics of NLR, they did not conduct quantitative analysis and did not arrive at a specific conclusion [ 60 , 61 ].…”

Prognostic Value of Preoperative Nutritional Assessment and Neutrophil-to-Lymphocyte Ratio in Patients With Thymic Epithelial Tumors

“…Additionally, inflammation plays an important role in the development and progression of cancer (11)(12)(13). Inflammationrelated indicators such as the systemic immune-inflammatory index (SII) and neutrophil-to-lymphocyte ratio (NLR) play a role in predicting prognosis in breast cancer (14), kidney cancer (15), lung cancer (16), esophageal cancer (17,18), and other tumors. Considering the close relationship between inflammation and tumor development, this study also assessed inflammationrelated factors.…”