Systemic Inflammatory Response and Survival in Patients with Localised Prostate Cancer: 10-Year Follow-UpMcArdle P.A. · Qayyum T. · McMillan D.C.
University Department of Surgery, Faculty of Medicine, University of Glasgow, Royal Infirmary, Glasgow, UK
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Article / Publication Details
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
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 . 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 .
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 . 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 . 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.
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