Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Systemic Inflammatory Response and Survival in Patients with Localised Prostate Cancer: 10-Year Follow-Up

McArdle P.A. · Qayyum T. · McMillan D.C.

Author affiliations

University Department of Surgery, Faculty of Medicine, University of Glasgow, Royal Infirmary, Glasgow, UK

Related Articles for ""

Urol Int 2010;84:430–435

Do you have an account?

Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 15, 2009
Accepted: December 22, 2009
Published online: April 15, 2010
Issue release date: May 2010

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 3

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: https://www.karger.com/UIN

Abstract

Aim: To examine the prognostic value of circulating C-reactive protein concentrations at diagnosis in patients with organ-confined prostate cancer. Patients and Methods: Ninety-eight patients with histologically proven clinically localised prostate cancer were studied. Clinical stage, tumour grade, circulating PSA and C-reactive protein concentrations at diagnosis were recorded. Results: The majority of patients was under the age of 70 years and had low-grade tumours. Approximately half the patients received radical local treatment. During the follow-up period (median 10 years) 38 patients died, of whom 18 died of prostate cancer, 6 of other cancers and 14 of non-cancer causes. On univariate survival analysis, age (p < 0.001), Gleason score (p < 0.05), C-reactive protein (p < 0.05) and treatment (p < 0.05) were significant predictors of overall survival. On univariate survival analysis, age (p < 0.001), Gleason score (p < 0.05) and C-reactive protein (p < 0.05) were significant predictors of prostate cancer-specific survival. On multivariate analysis of these significant variables age (HR 4.88, 95% CI 1.79–13.29, p < 0.01), Gleason score (HR 2.16, 95% CI 1.23–3.78, p < 0.01) and C-reactive protein (HR 1.88, 95% CI 1.01–3.52, p < 0.05) remained significant independent predictors of prostate cancer-specific survival. Conclusion: The results of the present study show that the presence of a systemic inflammatory response, at diagnosis, independently predicts poor long-term cancer outcome in patients with localised prostate cancer.

© 2010 S. Karger AG, Basel



 

Editorial Comment: A Tale Too Good to Be True



 

Philipp Dahm


Department of Urology, University of Florida College of Medicine, Health Science Center, Gainesville, Fla., USA

McArdle and coworkers examine the tantalizing hypothesis that C-reactive protein (CRP), an unspecific marker of inflammatory response, represents an important prognostic marker of long-term survival in patients with clinically localized prostate cancer. The authors analyzed a retrospective case series of 98 patients from a single center that were treated with a wide spectrum of modalities during an 8-year time period (1995–2002). One of the central findings of this study was the statistically significant associations of CRP levels and prostate cancer-specific survival (HR 1.88, 95% CI 1.01–3.32) and overall survival (HR 1.60, 95% CI 1.03–2.47) on multivariate analysis after a median follow-up of 10 years. The authors subsequently concluded that elevated CRP levels predicted a poor long-term outcome in patients with localized prostate cancer.

Which urologist would not welcome the news that CRP as an easily measurable marker with an established role in the management of many autoimmune diseases such as rheumatoid arthritis may also help predict the long-term fate of patients with clinically localized prostate cancer? Unfortunately, it is too early to celebrate. Instead, this study highlights the importance for urologists to critically appraise studies for their validity, impact and applicability. Using the structured framework proposed by the Users’ Guide to the Medical Literature, key limitations of this study will be highlighted [1, 2].


 

Are the Results Valid?


When reviewing questions of prognosis, the reader is encouraged to consider, among other things, whether the sample of patients was representative, whether they were sufficiently homogeneous with regard to prognostic risk, and whether outcome criteria were objective and unbiased [3]. Unfortunately, McArdle’s group provides little information to convince us that these criteria were met. Specifically, there is no information on how these patients were recruited into this study; the patients were treated with a wide variety of modalities, and the completeness of follow-up was not addressed.

Although the authors attempted to adjust for other known prognostic variables, such as clinical stage, Gleason score and PSA levels, the low absolute number of events in this study draws the appropriateness of the reported multivariable analysis into question. At the same time, the study failed to adjust for medical comorbidities, such as cardiovascular disease, which would be expected to have an impact on overall survival but also have a reported association with CRP levels [4].


 

What Are the Results?


The reported results for overall survival suggest patients with a CRP of >10 mg/l have a 1.6-fold risk of death over time than patients with a CRP of <10 mg/l. Meanwhile, there is considerable uncertainty about the true relative risk of patients with an elevated CRP level, as reflected by the wide confidence interval [5]. In fact, the true hazard ratio may be as low as 1.03 or has high 2.47. At the same time, the fact that clinical stage and pre-treatment did not predict overall or prostate cancer-specific survival is noteworthy.


 

How Can I Apply the Results to the Care of My Patients?


With regard to clinical applicability, the authors fail to provide any guidance on how their results – should they be valid – be applied clinically. Should patients with low-risk prostate cancer and an elevated CRP be treated aggressively and not be considered candidates for active surveillance? Vice versa, how should a low CRP level modify treatment in patients with intermediate and high-risk prostate cancer?


 

Clinical Bottom Line


In summary, the study by McArdle and coworkers has critical limitations and ultimately only provides very low quality evidence to suggest that CRP may have a prognostic role in prostate cancer. These conclusions parallel those of a recent study on breast cancer [6]. The findings of this study may be considered hypothesis-generating, but should not motivate urologists to draw CRP levels on their prostate cancer patients. Meanwhile, this study provides an excellent case study of why critical appraisal skills are integral to the evidence-based practice of urology.


 

References


1 Guyatt G, et al: Users’ Guide to the Medical Literature: A Manual for Evidence-Based Clinical Practice, ed 2. New York, American Medical Association, 2008.

2 Scales CD Jr, et al: Evidence-based clinical practice: a primer for urologists. J Urol 2007;178:775–782.

3 Dahm P, et al: Users’ guide to the urological literature: how to use an article about prognosis. J Urol 2010, in press.

4 Boffetta P: Exploring a cancer biomarker: the example of C-reactive protein. J Natl Cancer Inst 2010;102:142–143.

5 Breau RH, et al: Understanding results. J Urol 2009;181:985–992.

6 Zhang SM, et al: C-reactive protein and risk of breast cancer. J Natl Cancer Inst 2007;99:890–894.


References

  1. Cancer statistics, Cancer Research UK. www.cancerresearchuk.org.
  2. SEER Program and Monograph Data: National Cancer Institute. www.seer.cancer.gov.
  3. Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Adami HO, Johansson JE, Scandinavian Prostate Cancer Group Study Number 4: Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100:1144–1154.
  4. Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001;537:539–545.
    External Resources
  5. Coussens LM, Werb Z: Inflammation and cancer. Nature 2002;420:860–867.
  6. Vakkila J, Lotze MT: Inflammation and necrosis promote tumour growth. Nat Rev Immunol 2004;4:641–648.
  7. McMillan DC, Canna K, McArdle CS: A systemic inflammatory response predicts survival following curative resection for colorectal cancer. Br J Surg 2003;90:215–219.
  8. 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;92:21–23.
  9. Crumley ABC, McMillan DC, McKernan M, Going JR, Stuart RC: The relationship between the pre-operative systemic inflammatory response and cancer specific survival in patients undergoing potentially curative resection for gastro-oesophageal cancer. Br J Cancer 2006;94:1568–1571.
  10. Lamb GWA, McMillan DC, Ramsey S, Aitchison M: Pre-operative systemic inflammatory response predicts cancer specific survival in patients undergoing potentially curative resection for renal clear cell cancer. Br J Cancer 2006;94:781–784.
  11. Iimura Y, Saito K, Fujii Y, Kumagai J, Kawakami S, Komai Y, Yonese J, Fukui I, Kihara K: Development and external validation of a new outcome prediction model for patients with clear cell renal cell carcinoma treated with nephrectomy based on preoperative serum C-reactive protein and TNM classification: the TNM-C score. J Urol 2009;181:1004–1012.
  12. Hilmy M, Bartlett JM, 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;92:625–627.
  13. 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;101:978–981.
  14. McArdle PA, Mir K, Almushatat AS, Wallace AM, Underwood MA, McMillan DC: Systemic inflammatory response, prostate-specific antigen and survival in patients with metastatic prostate cancer. Urol Int 2006;77:127–129.
  15. Nakashima J, Kikuchi E, Miyajima A, Nakagawa K, Oya M, Ohigashi T, Murai M: Simple stratification of survival using bone scan and serum C-reactive protein in prostate cancer patients with metastases. Urol Int 2008;80:129–133.
  16. Beer TM, Lalani AS, Lee S, Mori M, Eilers KM, Curd JG, Henner WD, Ryan CW, Venner P, Ruether JD, Chi KN, ASCENT Investigators: C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer: results from the ASCENT trial. Cancer 2008;112:2377–2383.
  17. European Association of Urology: Guidelines on Prostate Cancer. www.uroweb.org.
  18. Ataman F, Zurlo A, Artignan X, van Tienhoven G, Blank LE, Warde P, Dubois JB, Jeanneret W, Keuppens F, Bernier J, Kuten A, Collette L, Pierart M, Bolla M: Late toxicity following conventional radiotherapy for prostate cancer: analysis of the EORTC trial 22863. Eur J Cancer 2004;40:1674–1681.
  19. Gabay C, Kushner I: Mechanisms of disease: acute phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448–454.
  20. Pepys MB, Hirschfield GM: C-reactive protein: a critical update. J Clin Invest 2003;111:1805–1812.
  21. Corcoran NM, Costello AJ: Interleukin-6: minor player or starring role in the development of hormone-refractory prostate cancer? BJU Int 2003;91:545–553.
  22. Okamoto M, Lee C, Oyasu R: Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. Cancer Res 1997;57:141–146.
  23. Lou W, Ni Z, Dyer K, Tweardy DJ, Gao AC: Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway. Prostate 2000;42:239–242.
  24. Chung TD, Yu JJ, Kong TA, Spiotto MT, Lin JM: Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 2000;42:1–7.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 15, 2009
Accepted: December 22, 2009
Published online: April 15, 2010
Issue release date: May 2010

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 3

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: https://www.karger.com/UIN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.