Abstract
C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression.
Highlights
Systemic inflammation plays an important role in various aspects of cancer involving cancer initiation, promotion, progression, metastasis and clinical features (Mantovani et al, 2008) and cancer-related inflammation has been recognized as the seventh hallmark of cancer (Colotta et al, 2009)
Our pooled results demonstrate that a high serum level of C-reactive protein (CRP) as an inflammation biomarker denotes a poor prognosis of patients with urological cancers
RCC, renal cell carcinoma; MRCC, metastatic RCC; LRCC, localized RCC; CC-RCC, clear cell RCC; UC, urethelial carcinoma; UTUC, upper urinary tract urothelial carcinoma; UUTUC, upper urinary tract urothelial carcinoma; MIBC, muscle invasive bladder cancer; PC, prostate cancer; LPC, localized PC; MCRPC, metastatic castration-resistant prostate cancer; P, prospective; R, retrospective; OS, overall survival; cancer-specific survival (CSS), cancer special survival; relapse-free survival (RFS), relapse free survival; HR, hazard ratio; TKI, tyrosine kinase inhibitors; ADT, androgen-deprivation therapy; NA, not available patients were segregated according to the disease (RCC, UC, and PC), region (European, Asian, and America), design of eligible studies, and sample size (>110 vs ≤110), high serum concentration of CRP was significantly correlated with OS, CSS and RFS (Table 2)
Summary
Systemic inflammation plays an important role in various aspects of cancer involving cancer initiation, promotion, progression, metastasis and clinical features (Mantovani et al, 2008) and cancer-related inflammation has been recognized as the seventh hallmark of cancer (Colotta et al, 2009). CRP has been shown to be significant in the prediction of outcomes of urological cancers, including renal cell carcinoma (RCC), upper urinary tract and bladder cancers (UC), and prostate cancer (PC). The elevation of C-reactive protein levels, which indicate the presence of cancer-associated systemic inflammatory response, is linked to poorer survival in patients with urological cancers, including renal cell carcinoma, upper urinary tract and bladder cancers, and prostate cancer. With this strong prognostic ability, C-reactive protein can be incorporated into prognostic models and will make them simpler and improve their predictive accuracy. We attempt to conduct a systematic review and meta-analysis to estimate the prognostic significance of elevated serum CRP levels for overall survival (OS) cancer special survival (CSS) and recurrence-free survival (RFS) on the basis of the currently available evidence in urological cancers, including RCC, UC and PC
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