Prognostic Role of Preoperative C-Reactive Protein in Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy - An Updated Meta-Analysis

Background: C-reactive protein (CRP) is an acute-phase protein that is mainly stimulated by the inflammation-associated cytokines and high concentrations of CRP have been detected in many tumors. Many studies have shown that there is a close correlation between CRP and the prognosis of upper urinary tract carcinoma (UTUC). However, the prognosis significance of CRP in UTUC is still controversial. Our study aims to perform an updated systematic review and meta-analysis to investigate the association between CRP and the prognostic value for UTUC undergoing radical nephroureterectomy (RNU).Methods: A comprehensive electronic database search, using PubMed, EMBASE, and Web of Science, was performed to identify relevant research articles published before April 2020. Strict inclusion and exclusion criteria were established to extract data. Newcastle-Ottawa Scale was used to assess the quality of all candidate studies. The pooled hazard ratios (HR) and 95% confidence intervals (CIs) for recurrence-free survival (RFS), cancer-specific survival (CCS), and overall survival (OS) were calculated to evaluate the intensity of association. And heterogeneity and publication bias were assessed. Moreover, to ensure the stability of the analysis results, a sensitivity analysis was tested. All data were analyzed by Stata 15.0 and Review Manager 5.3.Results: Thirteen studies including a total of 2801 patients were eligible for meta-analysis. Our results verified that elevated CRP predicted poorer FRS (pooled HR=1.38, 95%CIs：1.12-1.71, P=0.003), CCS (pooled HR=1.64, 95%CI：1.38-1.94, P<0.001), OS (pooled HR=1.35, 95%CIs: 1.03-1.79 ,P=0.03) in patients with UTUC after RNU. Besides, elevated CRP was overtly correlated with tumor pathological stage (T3/T4 vs. ≤T2: OR=3.40, 95% CIs 2.39-4.84, P<0.001), tumor grade ((1/2 vs. 3: OR=1.68, 95% CIs 1.24-2.28, P<0.001), lymph node involvement (LNI) (+ vs. -: OR=2.73, 95% CIs 1.80-4.14, P<0.001), lymphovascular invasion (LVI) (+ vs. -: OR=4.1, 95% CIs 2.26-7.44, P<0.001). And these results got after using sensitivity analysis were verified to be stable and reliable. Furthermore, Begg's test result (RFS: P=0.089, CCS: P=0.592, and OS: P=0.089) showed no significant publication bias in the procedure.Conclusion: Elevated CRP indicates a poor prognosis for patients with UTUC undergoing RNU. Elevated CRP plays a significant role in reasonable risk stratification and individualized treatment.