C-reactive protein as a prognostic marker FOR mCRPC
Article first published online: 23 APR 2012
© 2012 BJU INTERNATIONAL
Volume 110, Issue 11b, page E469, December 2012
How to Cite
Abern, M. R., Allott, E. H. and Freedland, S. J. (2012), C-reactive protein as a prognostic marker FOR mCRPC. BJU International, 110: E469. doi: 10.1111/j.1464-410X.2012.11156.x
- Issue published online: 22 JAN 2013
- Article first published online: 23 APR 2012
castration-resistant prostate cancer
The relationship between inflammation and cancer is a topic of intense study. On the one hand, immunotherapy, relying on the host mounting a cytotoxic immune response to the tumour, has shown a survival advantage for men with advanced prostate cancer. On the other hand, systemic inflammation may create a pro-tumour environment and portend a poor prognosis, as suggested by the data reported in the present study. Baseline C-reactive protein (CRP) is shown to offer a readily-available prognostic marker that performs as well as the best published nomograms for progression-free and overall survival in patients with castration-resistant prostate cancer (CRPC).
Why is CRP such a strong predictor of progression in men with late-stage disease? CRP is produced in the liver as a marker of host response to tissue damage, pathogens or inflammatory stimuli and, as such,is a marker of systemic inflammation. CRP transcription is primarily regulated by interleukin (IL)-6 and, to a lesser extent, by other pro-inflammatory cytokines . There is much interest in IL-6 because it is a pleiotropic pro-inflammatory, pro-tumour cytokine produced by a variety of cell types, including T lymphocytes, macrophages and endothelial cells, and it has been implicated in prostate cancer tumourigenesis, progression, androgen independence and bone metastasis . However, phase II results have shown minimal clinical activity of anti-IL-6 therapy (siltuximab) in patients with CRPC , indicating that more research is necessary.
Given the clear data reported in the present study showing that CRP is a strong predictor of outcome, what are the next steps? First, it has been shown that decreased levels of several biomarkers in response to therapy, which are prognostic of outcome at baseline (i.e. PSA levels and circulating tumour cells) portend a good prognosis. Thus, can correlating dynamic variations in serum markers such as CRP with traditional surrogate measures of response to therapy in CRPC offer a future application for assessing treatment efficacy in a setting where PSA levels have less utility? Indeed, this approach has been shown for CRP in other disease states, such as RCC, cardiovascular and orthopaedic diseases . Second, how do we explain why CRP predicts outcome for men with metastatic disease but does not predict a diagnosis of prostate cancer?  Third, is there a common mechanism that results in disease progression and CRP production?
In summary, the data show that CRP, which is cost-effective and non-invasive, can be used to accurately risk-stratify men with advanced prostate cancer. However, similar to any good study, this leaves us with more questions than answers.