Improving prostate cancer diagnosis with a simple blood test

Professor Aled Clayton (BSc 1993, PhD 1997) is based in Cardiff University’s School of Medicine and the Wales Cancer Research Centre. His research team, the Tissue Microenvironment Group, is a collection of dedicated and diverse researchers who aim to unlock vital information that will improve the way we diagnose and treat prostate cancer.

Professor Clayton’s research particularly focusses on prostate cancer which is the most common cancer in men in the UK. Every year around 50,000 men in the UK are diagnosed with prostate cancer, and whilst survival rates are around 78%, sadly the disease proves fatal for many, with one death happening every 45 minutes.

Despite the high occurrence, diagnosis and treatment, especially for advanced prostate cancer still have a long way to go. Unlike many cancers, there is no regular screening programme, and all too often men present with symptoms very late when the disease has already spread. Currently diagnosis is based on several tests, and is rather complex, needing teams of doctors, surgeons, pathologists, and laboratory biochemists. Simplifying diagnosis, and spotting the disease much earlier is what the team are trying to achieve.

Uncertainty in testing

Current testing begins by measuring levels of Prostate Specific Antigen, or PSA. This is a protein made by prostate cancer cells. However normal prostate cells also make PSA, so it is not a great test to identify cancer. Further, as the prostate may naturally grow with age, the levels of PSA can rise, and the levels of PSA can change from day to day, dependant on a range of factors.

Professor Clayton explains the questionable reliability of PSA testing and the impact this has on patients:
“There are national clinical excellence guidelines for what the levels of PSA in the blood should be in healthy men, and this level of “normal” goes up with age. PSA also fluctuates quite dramatically depending on what you’ve been doing. Riding a bike, sexual activity, and urological infections all effect levels of PSA. It can go up and down – so to try to make really sound clinical decisions based on PSA measurements alone is unwise. In order to establish whether the high level is indicative of something wrong, you might run the test again a month later. If you keep doing this, you get an idea if it’s consistently abnormal or if a rogue measurement was just a blip. During this time, there is a lot of uncertainty for the patient.”

This can translate to months of waiting and anxiety for men who may not even have prostate cancer, or more worryingly, cause potential delays to treatment for those that do. Once a pattern of high PSA levels is established, more tests are then conducted which include a digital rectal exam and an MRI scan. If these cause concern a needle biopsy of the prostate is then usually performed to provide the definitive diagnosis. Whist such additional tests are relatively quick procedures, biopsies are invasive and run the risk of infection. For between 1% and 3% of men the infections can be serious and require hospital admission.

“MRI scanning can give us additional information in terms of any abnormalities in the prostate and the lymph nodes close by and tell us where that abnormality is. We have some very sophisticated image analysis now, which can predict how aggressive the cancer may be. But for a proportion of patients the results of MRI are not always obvious, and patients may undergo a biopsy procedure that ultimately may be unnecessary.

“From the MRI information, there’s a zone where you’re safe, you’re probably okay and we don’t need to do a biopsy. There’s a zone where you definitely need to have a biopsy and likely start treatment immediately, because things are looking really worrying. And there’s this margin of error in the middle, where we are not sure. That’s a very difficult conversation to have with a patient. To say that we’re not sure and we don’t know how dangerous it is.”

Improving the future of diagnosis

It’s exactly this uncertainty that Professor Clayton and his research team are trying to overcome by developing a new diagnostic blood test. This test works by measuring proteins or RNA molecules present in the blood in small ‘vesicles’ which originate from the tumour tissue.

Vesicles are very small spherical structures that cells make to transfer instructions to other cells. They are essentially mini versions of the cell. Some of the vesicles find their way into the blood stream, or into the urine, and potentially offer a host of opportunities in diagnosis and disease monitoring.

“Cancer vesicles are distinct – they carry certain cancer features and reflect the state of stress or damage of the cell that made them. By analysing the vesicles we find in blood, we can look for the tell-tale signs of cancer much more easily, especially in relation to solid cancers that aren’t very accessible like lung, prostate or liver.”

The new blood test is hoped to help clinicians identify prostate cancer sooner, and because the test measures many molecules, and not just PSA, it holds potential to provide vital information about how a prostate cancer will develop.

“Our ambition is that this test will give doctors helpful information, allowing them to be more certain about the need for a biopsy. If the test works well, it may replace biopsy altogether – which would be a fantastic advance. It will ultimately help doctors make the right decision for an individual’s treatment, so they receive the very best outcomes and care.”

Looking ahead

Whilst it’s still early days, Professor Clayton is optimistic that this new diagnosis technique could be available to patients in as little as five years.

“At this stage there is a real need to upscale the data, so we can start building statistical confidence. We simply couldn’t do this without patients donating their blood and tissue samples for research purposes. It’s thanks to them, that we’re able to begin to tackle some of these important questions.

“Once we have confidence in the data, we can begin to rely on this testing more heavily and start making a real difference to diagnosis and treatment, ultimately saving and improving the lives of men with prostate cancer.”

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