Cell Cycle Progression (CCP) score

Cell Cycle Progression (CCP) score has been in the news recently which could possibly be used as a tool alongside the PSA test to identify the more aggressive types of prostate cancer,it's still early days but worth highlighting for future reference.

Prostate cancer 'gene test' hope
Posted on February 9, 2011
Experts believe they can develop a genetic screening test that can tell doctors which men with prostate cancer need aggressive treatment.

Early trial results for Cancer Research UK suggest men with high levels of cell cycle progression (CCP) genes have the most deadly tumours.

The CCP test could potentially save men with milder forms of the disease from unnecessary treatment.

Large-scale studies are now needed, the Lancet Oncology journal reports.

Prostate cancer is the most common cancer in men in the UK, with new cases diagnosed in around 37,000 men every year.

At present, doctors can struggle to predict how aggressive tumours are and rely on tests and examinations that can be less than reliable.

For example, one of the tests currently used - the Prostate Specific Antigen (PSA) test - can give a worrying result even if a cancer is not present.

Cancer Research UK estimates that about two-thirds of men with an elevated PSA level (measured as > 4ng/ml) will not have prostate cancer but will suffer the anxiety, discomfort and risk of follow-up investigations.

It's for this very reason that UK experts have recommended against a screening programme for prostate cancer.

But experts from Queen Mary, University of London, hope their new CCP test - alongside existing tests like PSA - could be used routinely in the clinic to overcome this problem.

Greater accuracy

Professor Jack Cuzick, who led the research, said: "Our findings have great potential. CCP genes are expressed at higher levels in actively growing cells, so we could be indirectly measuring the growth rate and inherent aggressiveness of the tumour through our test.

"We already know that CCP levels can predict survival for breast and, more recently, brain and lung cancers.

"It's really encouraging that this could also be applied to prostate cancer, where we desperately need a way to predict how aggressive the disease will be."

His study, which included 703 men with prostate cancer, found CCP could predict likely disease outcomes.

In the study, men with the highest levels of CCP genes were three times more likely than those with the lowest levels to have a fatal form of prostate cancer.

And for patients who have had surgery to remove their prostate, those with the highest CCP levels were 70% more likely to have a recurrence of the disease.

Dr Helen Rippon, head of research management at the Prostate Cancer Charity, said the findings were promising but needed replicating in larger trials before the test could be considered for routine use.

"It will therefore be some time before men diagnosed with prostate cancer will see any direct benefit from this research," she said.

Prostate cancer 'gene test' hope


Is CCP testing really the prognostic tool we need?

Posted on February 9, 2011

A new report just published on line in Lancet Oncology is suggesting that the cell cycle progression (CCP) score — a measure of the levels of expression of selected genes that are important to cell growth — may be an important indicator of risk for more aggressive types of prostate cancer.

The article by Cuzick et al. describes a study to investigate the prognostic value of a predefined CCP score in tissue samples from three existing cohorts of patients with prostate cancer. Two cohorts of patients (in the USA) had already undergone a radical prostatectomy to treat their disease; the third cohort of patients (in the UK) were initially diagnosed as a consequence of a transurethral resection of the prostate (a TURP) and then followed until death. It is very important to understand that the data from this study are retrospective and not prospective.

Cuzick and his colleagues initially measured the levels of expression of a total of 31 genes involved in CCP. They used these data to develop a predefined CCP “score” and then they set out to evaluate the value of the CCP score in predicting risk for progressive disease in the men who had undergone an RP or risk of prostate cancer-specific mortality in the men who had been diagnosed by a TURP and managed by watchful waiting.

The findings of this study can be summarized as follows:

•Among patients in the two RP cohorts
◦The CCP score could predict biochemical recurrence in univariate analysis (hazard ratio [HR] for a doubling in CCP = 1·89; p=5·6×10−9).
◦The CCP score could predict biochemical recurrence in the final multivariate analysis (HR =1·77; p=4·3×10−6).
◦The CCP score and the PSA level were the most important and the most clinically significant variables in the best predictive model (the final multivariate analysis).
•Among patients in the TURP cohort
◦The CCP score could predict time to death from prostate cancer in univariate analysis (HR = 2·92; p=6·1×10−22).
◦The CCP score could predict time of death from prostate cancer in the final multivariate analysis (HR = 2·57; p=8·2×10−11).
◦The CCP score was stronger than all other prognostic factors (although PSA levels added useful information).
Clearly the CCP score is an important prognostic marker of risk for progressive prostate cancer. However, it would be wise of us to have some degree of caution about interpreting exactly what this study is telling us.

In the first place, at this time, we have no prospective validation of the data from this study. To get such validation, ideally, one would want to be able to:

•Assess CCP scores based on data from biopsy specimens of patients
•Assess CCP scores based on data from subsequent RP specimens from the same patients
•Compare the predictions of the two sets of CCP scores to actual outcomes over time.
In addition, simple biochemical recurrence would not be sufficient. We would ideally need to know data from biochemical recurrence before and after first- and second-line therapy and the PSA doubling times (or some other measure of rate of progression) in order to have a clear picture of the aggressiveness of the cancer post-treatment. Such a study could take a while.

A Reuters commentary on this paper points out that a test is already available that would allow commercialization of CCP score testing. This is the Prolaris test available from Myriad Genetics. (It is not clear yet, but it may well have been a modified version of the Prolaris test that was used to assess CCP scores in the study by Cuzick et al.) We commented on the potential of the Prolaris test about a year ago.

At the very end of the Reuters commentary, Reuters quotes Dr. Helen Rippon, the head of research management for the British Prostate Cancer Charity, as saying that CCP testing would need to be “comprehensively trialed in large numbers of men before it can be introduced into routine clinical practice.”

The “New” Prostate Cancer InfoLink is in complete agreement with Dr. Rippon. However exciting the possibility of CCP testing looks, based on the data available to date, we still need careful and comprehensive prospective studies to demonstrate that this type of testing is really able to discriminate with high levels of accuracy between clinically significant and clinically insignificant forms of prostate cancer. Retrospective data of the type reported in Lancet Oncology is interesting — but not clinically definitive at all.

Is CCP testing really the prognostic tool we need?