Gene test may cut need for prostate cancer surgery
Tue Feb 8, 2011 7:01pm EST
* Study finds gene levels can identify aggressive cancers
* Testing could help thousands avoid unnecessary surgery
* Test already developed by U.S-based Myriad Genetics
* Prostate cancer killed about 258,000 men in 2008
By Kate Kelland [Reuters]
LONDON, Feb 9 (Reuters) - A genetic pattern could predict how aggressive prostate cancer is, potentially saving many men with less threatening tumours from undergoing unnecessary and life changing surgery, scientists said on Wednesday.
Prostate tumours can range from relatively harmless ones that grow very slowly and are unlikely ever to cause a problem, to ones that are far more aggressive and need swift treatment. At present doctors have few effective tools to differentiate between varying types.
British researchers found that men with the highest levels of "cell cycle progression" (CCP) genes -- ones that encourage cells to grow -- were three times more likely than those with the lowest levels to have a fatal form of prostate cancer.
The study, published in the Lancet Oncology journal, also found that in patients who had already had surgery to remove their prostate, those with the highest CCP levels were 70 percent more likely to have a recurrence of the disease.
"Our findings have great potential," said Jack Cuzick, a cancer specialist based at Queen Mary, University of London.
"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 a test."
Myriad Genetics (MYGN.O) in the United States, has developed a test called Prolaris which measures CCP levels and Cuzick said that if further trials confirm his results, doctors could be using it in prostate cancer patients within a year.
Prostate cancer killed an estimated 258,000 men around the world in 2008 and is the second most common cause of cancer death in men in the United States. In Britain, about 35,000 men are diagnosed with it and some 10,000 die from the disease each year.
Being able to distinguish between aggressive tumours and slow-growing ones could spare many men unnecessary treatment and side effects like impotence and incontinence.
The study looked at 703 men with prostate cancer -- 366 men in America who had undergone surgery to remove the prostate, and 337 men in Britain with cancer that was confined to the prostate and were judged to not need immediate treatment.
The untreated group were given what is called a "watch and wait" option, which allows doctors to try to avoid treating men whose prostate cancer will not cause them significant problems. Tissue samples from the prostate were either taken during surgery or from the biopsy used to diagnose the disease.
Researchers then tested each sample for levels of 31 different genes involved in CCP and were able to show that specific combination of these gene levels can identify men at high or low risk of the disease spreading beyond the prostate and those most likely to die.
Cuzick said previous studies had already shown that CCP levels can predict survival for breast, brain and lung cancers.
Helen Rippon, head of research management, at the British Prostate Cancer Charity, said in a statement the technology must be "comprehensively trialled in large numbers of men before it can be introduced into routine clinical practice". (Editing by Matthew Jones)
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The Lancet Oncology, Early Online Publication, 9 February 2011
Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study
Prof Jack Cuzick PhD a ‡, Gregory P Swanson MD b ‡, Gabrielle Fisher PhD a, Arthur R Brothman PhD c, Daniel M Berney FRCPath d, Julia E Reid MStat e, David Mesher MSc a, VO Speights MD f, Elzbieta Stankiewicz MSc d, Christopher S Foster MD g, Henrik Møller MD h, Peter Scardino MD i, Jorja D Warren BA e, Jimmy Park BS e, Adib Younus BS e, Darl D Flake MS e, Susanne Wagner PhD e, Alexander Gutin PhD e, Jerry S Lanchbury PhD e, Steven Stone PhD e, on behalf of the Transatlantic Prostate Group
Summary
Background
Optimum management of clinically localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease. To predict disease aggressiveness, clinicians combine clinical variables to create prognostic models, but the models have limited accuracy. We assessed the prognostic value of a predefined cell cycle progression (CCP) score in two cohorts of patients with prostate cancer.
Methods
We measured the expression of 31 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumour samples, and created a predefined score and assessed its usefulness in the prediction of disease outcome. The signature was assessed retrospectively in a cohort of patients from the USA who had undergone radical prostatectomy, and in a cohort of randomly selected men with clinically localised prostate cancer diagnosed by use of a transurethral resection of the prostate (TURP) in the UK who were managed conservatively. The primary endpoint was time to biochemical recurrence for the cohort of patients who had radical prostatectomy, and time to death from prostate cancer for the TURP cohort.
Findings
After prostatectomy, the CCP score was useful for predicting biochemical recurrence in the univariate analysis (hazard ratio for a 1-unit change [doubling] in CCP 1·89; 95% CI 1·54—2·31; p=5·6×10-9) and the best multivariate analysis (1·77, 1·40—2·22; p=4·3×10-6). In the best predictive model (final multivariate analysis), the CCP score and prostate-specific antigen (PSA) concentration were the most important variables and were more significant than any other clinical variable. In the TURP cohort, the CCP score was the most important variable for prediction of time to death from prostate cancer in both univariate analysis (2·92, 2·38—3·57, p=6·1×10-22) and the final multivariate analysis (2·57, 1·93—3·43; p=8·2×10-11), and was stronger than all other prognostic factors, although PSA concentration also added useful information. Heterogeneity in the hazard ratio for the CCP score was not noted in any case for any clinical variables.
Interpretation
The results of this study provide strong evidence that the CCP score is a robust prognostic marker, which, after additional validation, could have an essential role in determining the appropriate treatment for patients with prostate cancer.
Funding
Cancer Research UK, Queen Mary University of London, Orchid Appeal, US National Institutes of Health, and Koch Foundation. |
