Background: Numerous studies show that the pretreatment neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of patients with RCC. However, their findings are inconsistent, urging us to explore the prognostic value of NLR in RCC patients.
Methods: This study was pre-registered in PROSPERO (CRD42020167131). Two reviewers independently performed a systematical search of PubMed, Web of Science, EMBASE, and Cochrane Library databases for prospective or retrospective cohort studies investigating the prognostic value of pretreatment NLR. Hazard ratios with 95% confidence intervals for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and other useful clinicopathological features were extracted and analyzed with fixed or random-effect models by using Review Manager 5.3 and Stata 12.0 software. Heterogeneity was estimated on the basis of Cochran's Q test and I2 value. Sensitivity analyses and subgroup analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger's tests. The quality of the evidence was evaluated in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
Results: Overall, 6461 RCC patients from 24 retrospective studies and 1 prospective study were included. In overall population, elevated pretreatment NLR was associated with poorer OS (pooled HR = 1.90, 95% CI = 1.56-2.30, p < 0.001; I2 = 87%), DFS/PFS (pooled HR = 2.09, 95% CI: 1.49-2.94, p < 0.001; I2 = 99%), and CSS (pooled HR = 2.31, 95% CI: 1.61-3.33, p < 0.001; I2 = 14%). Furthermore, this negative association was further confirmed in patients with nonmetastatic and metastatic RCC patients, respectively. We also investigated the predictive role of NLR in metastatic RCC patients treated with immune checkpoint inhibitors (ICIs). The results indicated that the level of NLR was significantly associated with OS (pooled HR = 3.92, 95% CI: 2.00-7.69, p < 0.001; I2 = 0%) and PFS (pooled HR = 2.20, 95% CI: 95% CI: 1.61-3.01, p < 0.001; I2 = 20%).
Conclusions: This study demonstrated that elevated pretreatment NLR was significantly associated with poor prognosis of RCC patients. NLR could be helpful as a potential prognostic biomarker to guide clinical decision-making and select individualized treatment strategies for RCC patients.
Keywords: Biomarker; Inflammation; Kidney neoplasms; Meta-analysis; Neutrophil-lymphocyte ratio; Prognosis; Survival.