Improving Prostate Cancer Diagnosis

Prostate cancer has now overtaken breast cancer for the greatest annual number of fatalities caused by cancer and continues to be the most diagnosed type of cancer for men. Across the UK, 44,000 men are diagnosed each year¹ with one person dying every 45 minutes¹.

Over half of men aged 60 have prostate cancer, but only 10% of these will be at risk of becoming serious.

Prostate cancer symptoms can differ but common signs include presence of blood in the urine, going to the toilet many times a night and lower abdominal pain. These symptoms can be related to other things, but there is a chance it is prostate cancer.

One way to detect prostate cancer is by using the PSA test. This measures how much prostate specific antigen (PSA) you have in your blood. If PSA levels are raised, it could be a sign of prostate cancer. A problem with the PSA test is that it detects both indolent and aggressive prostate cancer.

At the time of diagnosis around a quarter of men are diagnosed as having indolent disease while a quarter will be told they have aggressive disease. For the remainder accounting for nearly 250,000 cases in Europe and North America each year it is not possible to distinguish potentially life-threatening disease (“the tigers) which can grow rapidly from harmless prostate cancer (“the pussycats) which grow very slowly and are never life-threatening.

The distinction between the tiger cancers and the pussycat cancers is important. A man with aggressive disease may be treated by having their whole prostate removed. The prostate effectively acts as the centre of plumbing, so treatment side-effects can be life changing.

Other treatments for aggressive disease include hormone therapy, and radiotherapy, but there is still a strong chance of life-changing side effects. Patients with indolent disease are put on active surveillance where the disease is monitored closely over time.

What has UEA research done?

UEA, however, have been looking at the much needed aspect of distinguishing the aggressive from the passive prostate cancer.

Researchers including Prof Colin Cooper, Dr Dan Brewer, Prof Vincent Moulton and Dr Bogdan Luca have created a new mathematical approach that has moved us closer to telling the difference, meaning thousands of lives could be saved from life-altering treatment. To do this, they used up to 10% of UEA’s total computing power over a one year period.

Prof Cooper said:

Previously, distinguishing the dangerous ‘tigers’ from the less threatening ‘pussycats’ has not been possible for many men.

“Curative treatment of early prostate cancer by surgery or radiotherapy needs to ideally be targeted to the minority of men with significant cancers, so that the remainder are spared the side-effects of treatment, which frequently includes impotence.

“Improved clinical markers are therefore required to predict behaviour allowing radical therapies to be targeted to men with significant cancers, so that the remainder, with biologically unimportant disease, are spared the side-effects of treatment.”

From the mathematical test, UEA have been able to identify a ‘poor prognosis’ category of human prostate cancer called DESNT. This has been a real breakthrough and has highlighted that the long search for classification of prostate cancer has been unsuccessful due to an incorrect mathematical test being applied.

Latent Process Decomposition (LPD) is a method used to assess the structure of a dataset without knowing the clinical outcome. The team modelled gene expression in the cancer samples, allowing a common process to be established.

Prof Moulton said:

“So far, mathematical approaches to categorising prostate cancers hasn’t worked because of the diverse make-up of the samples, but by applying the LPD process, we revealed we could group cancers which shared common traits, and designated them DESNT cancers.”

Prof Cooper said: “The existence of this distinction is a significant step in assisting in the targeting of appropriate therapy, and helping to avoid over-treatment.”

The next steps will be for the multidisciplinary team to develop this new method alongside other universities and work towards putting an end to the uncertainty that 250,000 men a year feel about whether they have life-threatening prostate cancer or not. This will lead to better prognosis and more confidence in what treatment is suitable.

Related research

Prof Cooper and Dr Brewer have performed mathematical analyses and provided scientific knowledge to the world’s largest study into genes which drive prostate cancer. This study has found 80 molecular weaknesses (in proteins) that could be targeted by drugs to help with the treatment of this life-changing disease.

They’ve found that 11 out of the 80 proteins could be targeted by drugs already in use and 7 by drugs in clinical trials. The remaining 62 are potentials to explore.

Prof Cooper said:

The study provides an important step towards personalising treatment for men with prostate cancer. We have identified many pathways by which this cancer develops, for which new drugs can be used to disrupt those pathways and potentially improve treatment.

Read the press release in full:

¹ www.prostatecanceruk.org/prostate-information/about-prostate-cancer