THE "NEW" PROSTATE CANCER INFOLINK

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.

Filed under: Diagnosis, Management, Risk | Tagged: aggressive, CCP, cell cycle progression, prognosis, PROLARIS, score |