title: Inflammatory prognostic markers in clear cell renal cell carcinoma - preoperative C-reactive protein does not improve predictive accuracy.
abstract: What's known on the subject? and What does the study add? White blood cell count and C-reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut-offs for risk stratifications are missing. Therefore, both parameters were re-evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer-specific mortality. However, this CRP-based prediction added no additional information compared to a clinico-pathological based model.
  
  
  OBJECTIVE
  To re-evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C-reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP.
  
  
  METHODS
  From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer-specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c-index).
  
  
  RESULTS
  In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/μL (hazard ratio [HR] 1.83) and 11.0/μL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P < 0.001) and 0.5 mg/dL (HR 7.15, P < 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer-specific survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumour-related deaths. The final model built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c-index 0.877) compared with the clinicopathological base model (c-index 0.881) which included TNM stage, grading and Karnofsky index.
  
  
  CONCLUSIONS
  Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was best to stratify patients at risk of cancer-specific mortality, but CRP 0.25 mg/dL added no additional information in the prediction model. Therefore we cannot recommend measuring CRP as the traditional parameters of TNM stage, grading and Karnofsky index are already of high predictive accuracy.
authors.affiliation: Department of Urology, Eberhard-Karls-University Tuebingen, Germany. bedke@live.com
authors.forename: Jens
authors.initials: J
authors.lastname: Bedke
authors.forename: Felix K-H
authors.initials: FK
authors.lastname: Chun
authors.forename: Axel
authors.initials: A
authors.lastname: Merseburger
authors.forename: Marcus
authors.initials: M
authors.lastname: Scharpf
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kasprzyk
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Karl-Dietrich
authors.initials: KD
authors.lastname: Sievert
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Stephan
authors.initials: S
authors.lastname: Kruck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000401:mortality / Q000601:surgery; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007680:Kidney Neoplasms / Q000097:blood* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: D002097:C-Reactive Protein