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Serum C-reactive protein: a prognostic factor in metastatic urothelial cancer of the bladder

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Abstract

Until today, there is no reliable prognostic or predictive parameter for the prognosis of patients with metastatic urothelial cancer of the bladder prior to chemotherapy. Recently, serum C-reactive protein (CRP) level has been shown to be associated with survival of patients with various malignancies including localized and metastatic renal cell carcinoma, upper urinary tract as well as penile cancer. The aim of this study was to evaluate the prognostic impact of the pretreatment CRP serum level in patients with metastatic urothelial cancer of the bladder. We retrospectively evaluated 34 patients with metastatic urothelial cancer of the bladder and information about the CRP level prior to chemotherapy. The CRP level was correlated with patient- and tumor-specific characteristics. Kaplan–Meier and log-rank analyses were employed to calculate progression-free (PFS) and overall survival (OS). Receiver operating characteristics (ROC) analysis was used to determine an optimal prognostic CRP cutoff value to predict cancer-specific death. The median PFS to first-line chemotherapy and the OS for the whole cohort were 3.3 and 24.3 months, respectively. Serum CRP in mg/l was significantly associated with patients’ survival (HR 1.02, p < 0.001, univariate Cox-regression). ROC analysis identified a CRP value of 80 mg/l to be the optimal cutoff. The median PFS was 4.5 and 3.0 months (p = 0.08; Mann–Whitney test), and the calculated 1-year OS was 82.6 and 22.2 % for patients with a CRP <80 and ≥80 mg/l, respectively (log-rank, p < 0.001). In contrast, neither T-stage, tumor grade, sex, age nor the body mass index was related to the CRP level or associated with overall survival. This is the first analysis revealing that the CRP value prior to systemic treatment might be of prognostic significance and could enable better risk stratification for patients with metastatic urothelial cancer of the bladder.

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References

  1. Allin KH, Bojesen SE, Nordestgaard BG. Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol. 2009;27:2217–24.

    Article  CAS  PubMed  Google Scholar 

  2. Canna K, McArdle PA, McMillan DC, McNicol A-M, Smith GW, McKee RF, McArdle CS. The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer. 2005;92:651–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Drachenberg DE, Elgamal AA, Rowbotham R, Peterson M, Murphy GP. Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate. 1999;41:127–33.

    Article  CAS  PubMed  Google Scholar 

  4. Eustace D, Han X, Gooding R, Rowbottom A, Riches P, Heyderman E. Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. Gynecol Oncol. 1993;50:15–9.

    Article  CAS  PubMed  Google Scholar 

  5. Gakis G, Todenhöfer T, Renninger M, Schilling D, Sievert K-D, Schwentner C, Stenzl A. Development of a new outcome prediction model in carcinoma invading the bladder based on preoperative serum C-reactive protein and standard pathological risk factors: the TNR-C score. BJU Int. 2011;108:1800–5.

    Article  CAS  PubMed  Google Scholar 

  6. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, de Vere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349:859–66.

    Article  CAS  PubMed  Google Scholar 

  7. Guillem P, Triboulet JP. Elevated serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer. Dis Esophagus. 2005;18:146–50.

    Article  CAS  PubMed  Google Scholar 

  8. Heikkilä K, Harris R, Lowe G, Rumley A, Yarnell J, Gallacher J, Ben-Shlomo Y, Ebrahim S, Lawlor DA. Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control. 2009;20:15–26.

    Article  PubMed  Google Scholar 

  9. Hilmy M, Bartlett JMS, Underwood MA, McMillan DC. The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer. 2005;92:625–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Jabs WJ, Busse M, Krüger S, Jocham D, Steinhoff J, Doehn C. Expression of C-reactive protein by renal cell carcinomas and unaffected surrounding renal tissue. Kidney Int. 2005;68:2103–10.

    Article  CAS  PubMed  Google Scholar 

  11. Jamieson NB, Glen P, McMillan DC, McKay CJ, Foulis AK, Carter R, Imrie CW. Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005;92:21–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Johnson TV, Abbasi A, Owen-Smith A, Young A, Ogan K, Pattaras J, Nieh P, Marshall FF, Master VA. Absolute preoperative C-reactive protein predicts metastasis and mortality in the first year following potentially curative nephrectomy for clear cell renal cell carcinoma. J Urol. 2010;183:480–5.

    Article  CAS  PubMed  Google Scholar 

  13. Mahmoud FA, Rivera NI. The role of C-reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep. 2002;4:250–5.

    Article  PubMed  Google Scholar 

  14. McMillan DC, Canna K, McArdle CS. Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg. 2003;90:215–9.

    Article  CAS  PubMed  Google Scholar 

  15. Miki S, Iwano M, Miki Y, Yamamoto M, Tang B, Yokokawa K, Sonoda T, Hirano T, Kishimoto T. Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett. 1989;250:607–10.

    Article  CAS  PubMed  Google Scholar 

  16. Okamoto M, Hattori K, Oyasu R. Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell lines in vitro. Int J Cancer. 1997;72:149–54.

    Article  CAS  PubMed  Google Scholar 

  17. Saito K, Kihara K. C-reactive protein as a biomarker for urological cancers. Nat Rev Urol. 2011;8:659–66.

    CAS  PubMed  Google Scholar 

  18. Saito K, Kawakami S, Ohtsuka Y, Fujii Y, Masuda H, Kumagai J, Kobayashi T, Kageyama Y, Kihara K. The impact of preoperative serum C-reactive protein on the prognosis of patients with upper urinary tract urothelial carcinoma treated surgically. BJU Int. 2007;100:269–73.

    Article  CAS  PubMed  Google Scholar 

  19. Stark JR, Li H, Kraft P, Kurth T, Giovannucci EL, Stampfer MJ, Ma J, Mucci LA. Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. Int J Cancer. 2009;124:2683–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Steffens S, Köhler A, Rudolph R, Eggers H, Seidel C, Janssen M, Wegener G, Schrader M, Kuczyk MA, Schrader AJ. Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients. BMC Cancer. 2012;8(12):399. doi:10.1186/1471-2407-12-399.

    Article  Google Scholar 

  21. Stein B, Schrader AJ, Wegener G, Seidel C, Kuczyk MA, Steffens S. Preoperative serum C-reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma. BMC Cancer. 2013;13:101.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666–75.

    CAS  PubMed  Google Scholar 

  23. Trichopoulos D, Psaltopoulou T, Orfanos P, Trichopoulou A, Boffetta P. Plasma C-reactive protein and risk of cancer: a prospective study from Greece. Cancer Epidemiol Biomark Prev. 2006;15:381–4.

    Article  CAS  Google Scholar 

  24. Weinstein PS, Skinner M, Sipe JD, Lokich JJ, Zamcheck N, Cohen AS. Acute-phase proteins or tumour markers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic diseases. Scand J Immunol. 1984;19:193–8.

    Article  CAS  PubMed  Google Scholar 

  25. Yoshida S, Saito K, Koga F, Yokoyama M, Kageyama Y, Masuda H, Kobayashi T, Kawakami S, Kihara K. C-reactive protein level predicts prognosis in patients with muscle-invasive bladder cancer treated with chemoradiotherapy. BJU Int. 2008;101:978–81.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Hendrik Eggers

  2. Department of Oncology, Hematology, Bone Marrow Transplantation, Pneumology, University Medical Center Eppendorf, Hamburg, Germany

    Christoph Seidel

  3. Department of Urology, Ulm University Medical Center, Ulm, Germany

    Andres Jan Schrader

  4. Department of Urology and Urologic Oncology, Hannover Medical School, Hannover, Germany

    Rieke Lehmann, Markus A. Kuczyk & Sandra Steffens

  5. Cancer Center, Hannover Medical School, Hannover, Germany

    Gerd Wegener

  6. Department of Oncology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Hendrik Eggers

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  1. Hendrik Eggers
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  2. Christoph Seidel
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  3. Andres Jan Schrader
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  4. Rieke Lehmann
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  6. Markus A. Kuczyk
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  7. Sandra Steffens
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Correspondence to Hendrik Eggers.

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Hendrik Eggers and Christoph Seidel have contributed equally to this work.

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Eggers, H., Seidel, C., Schrader, A.J. et al. Serum C-reactive protein: a prognostic factor in metastatic urothelial cancer of the bladder. Med Oncol 30, 705 (2013). https://doi.org/10.1007/s12032-013-0705-6

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  • DOI: https://doi.org/10.1007/s12032-013-0705-6

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