Prognostic significance of elevated pretreatment systemic inflammatory markers for patients with prostate cancer: a meta-analysis

Abstract

Background: Pretreatment inflammatory factors, including neutrophil, lymphocyte, platelet and monocyte counts as well as the ratios between them such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) have been suggested as potential prognostic predictors for patients with prostate cancer (PCa). However, the prognostic effects remain controversial. Therefore, the goal of this study was evaluate the prognostic values of these markers for PCa patients using a meta-analysis.

Methods: Potentially relevant publications in PubMed and Cochrane Library were searched. Pooled hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), recurrence free survival (RFS) and distant metastases-free survival (DMFS) were determined using a fixed or random effects model by STATA 13.0 software.

Results: Thirty-two studies involving 21,949 participants were included. Our pooled results demonstrated that a high pretreatment NLR (HR = 1.55, 95% CI 1.37-1.76), PLR (HR = 1.72; 95% CI 1.36-2.18), neutrophil (HR = 1.10; 95% CI 1.03-1.18 and monocyte counts (HR = 2.25; 95% CI 1.67-3.05) predicted inferior OS, while elevated pretreatment LMR (HR = 2.27; 95% CI 1.76-2.94) was correlated with favorable OS. Furthermore, the higher NLR (HR = 1.62; 95% CI 1.29-2.04) and monocyte counts (HR = 1.75; 95% CI 1.36-2.25), but lower LMR predicted worse PFS (HR = 2.18; 95% CI 1.58-3.02); poor RFS was only associated with NLR (HR = 1.12; 95% CI 1.04-1.20). The subgroup analysis showed that the higher NLR may be a predictive factor for OS only in patients with mCRPC and undergoing chemotherapy; while the higher PLR was only significantly associated with OS in localized PCa regardless of treatment.

Conclusion: This meta-analysis reveals that pretreatment NLR, PLR, LMR, neutrophil, and monocyte counts may be effective predictive biomarkers for prognosis in patients with PCa.

Keywords: Inflammatory markers; Meta-analysis; Prognosis; Prostate cancer.

Fig. 1

Flow diagram of study identification

Fig. 2

Forest plots of the significant correlations of neutrophil to lymphocyte ratio with survival. a Overall survival; b progression-free survival; c recurrence-free survival. Squares are hazard ratio (HR); horizontal lines are 95% confidence intervals (CI); blue diamond indicates the pooled HR estimate with its 95% CI

Fig. 3

Forest plots of the significant correlation of platelet to lymphocyte ratio with overall survival. Squares are hazard ratio (HR); horizontal lines are 95% confidence intervals (CI); blue diamond indicates the pooled HR estimate with its 95% CI

Fig. 4

Forest plots of the significant correlation of lymphocyte to monocyte ratio with survival. a Overall survival; b progression-free survival. Squares are hazard ratio (HR); horizontal lines are 95% confidence intervals (CI); blue diamond indicates the pooled HR estimate with its 95% CI

Fig. 5

Forest plots of the significant correlation of neutrophil counts with overall survival. Squares are hazard ratio (HR); horizontal lines are 95% confidence intervals (CI); blue diamond indicates the pooled HR estimate with its 95% CI

Fig. 6

Forest plots of the significant correlation of monocyte counts with survival. a Overall survival; b progression-free survival. Squares are hazard ratio (HR); horizontal lines are 95% confidence intervals (CI); blue diamond indicates the pooled HR estimate with its 95% CI

Fig. 7

Funnel plot for the assessment of potential publication bias. a Egger’s funnel plot for overall survival of NLR; b Trim-and-fill funnel plot for overall survival of NLR. SND standard normal deviation, s.e. standard error, CI confidence intervals

Fig. 8

Sensitivity analysis. The horizontal axis was ln(HR). The two ends of every broken line represent the 95% CI