Men may soon find it easier to decide whether to have surgery for prostate cancer, thanks to two tests that distinguish the aggressive form of the disease from the much milder version.
Until now, the most common check for prostate cancer has been the PSA test, which detects a cancer-related protein in blood called prostate-specific antigen.
But doctors in the US were told to stop offering the test in 2011 after it emerged that many men had milder forms of the disease that would not have progressed, yet received unnecessary treatment. This treatment resulted in urinary incontinence, erectile dysfunction or both for 40 in every thousand men. Fierce arguments have continued over the merits of the PSA test.
For the first time, two novel tests may make it possible to avoid such unnecessary treatment.
“We want to identify the ‘tigers’ so we can treat them,” says Hayley Whitaker at the University of Cambridge.
To do so, Whitaker and her colleagues analysed biopsies taken from 104 British men who’d had parts of their prostate removed owing to cancer between 2001 and 2005. They identified greater amounts of a protein called NAALADL2 in the 38 men who later developed secondary tumours.
Of the men whose cancer reappeared, 86 per cent had a high level of protein in their initial biopsies.
The same pattern emerged when the team screened biopsies from 252 Swedish men who’d had their prostates removed between 1998 and 2002, 101 of whom had since relapsed.
Further investigation showed that NAALADL2 helps cancer cells to break out of the prostate and spread to form secondary cancers elsewhere in the body.
“The protein is produced where the prostate gland comes into contact with the cells and tissue surrounding it,” says Whitaker. “It promotes movement of cells from the prostate into neighbouring tissue, and out into the bloodstream.”
In blood tests, Whitaker’s team was able to detect the messenger RNA that makes the protein. The team is also hopeful that the protein itself may be detectable in this way.
Meanwhile, promising results from another test, called Prolaris, were presented earlier this month in Liverpool, at the annual meeting of the UK National Cancer Research Institute.
This test gives a “cell cycle progression” (CCP) score, measured by analysing biopsies to find the activity of 46 genes known to be linked with multiplication of prostate cancer cells. The more active they are, the more likely it is that the cancer is multiplying and spreading aggressively.
“It’s a very robust method of determining the risk of mild or serious disease based on how rapidly cells are dividing,” says Jack Cuzick of Queen Mary, University of London, lead author of a study that evaluated the test in 1606 men.
Because the biopsies were all taken when the men began treatment between 10 and 15 years ago, Cuzick and his colleagues were able to confirm that CCP scores were highest in men who eventually developed aggressive cancers.
Whitaker says that these tests could be used alongside one another. She envisions initial screening of men between their mid-40s and early 50s for genes identified by Rosalind Eeles of the Institute of Cancer Research in London as raising the risk of aggressive prostate cancer. Men who test positive for that could then receive PSA tests and, if these are positive, either or both of the alternative tests could be applied to see if the cancer is aggressive or mild.
Taken together, she thinks the tests will vastly reduce the number of unnecessary treatments. “I think we’re moving in leaps and bounds in the right direction, but the big thing now is to validate both these tests in larger cohorts.”
Journal reference: Oncogene, DOI: 10.1038/onc.2013.464
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