Case study: Transforming prostate cancer diagnosis for men around the world
Dramatically improving prostate cancer diagnosis
In April 2019, the National Institute for Clinical Excellence (NICE) advised that all men at risk of prostate cancer should have an MRI before a biopsy. This was, claims Professor Mark Emberton of University College London Hospital, the biggest diagnostic development in prostate cancer diagnosis for 50 years.
The change has been echoed around the world and is the result of two trials supported by the NIHR, the first being the prostate MR imaging study (PROMIS), funded by the NIHR Health Technology Assessment (HTA) programme. PROMIS, which took place in 2016, showed that a magnetic resonance imaging (MRI) scan has a 93 percent chance of detecting clinically relevant cancer compared to the previous test, biopsy, which had a success rate of 43 percent.
Professor Emberton says: “This is amazing in medicine. Just a ten percent improvement is a wow and this is 100 percent. We cannot overstate the impact of the PROMIS trial globally.”
A clearer picture of the invisible cancer
Prostate cancer is the most common cancer in men in the UK, most commonly affecting men over 50. There is no single test but men with symptoms, who are at high risk or who have suspected prostate cancer can be given a blood test, a physical examination, a biopsy and as of April 2019, an MRI.
Standard practice has been to biopsy men at risk: those who had a raised prostate specific antigen (PSA) in a blood test, men with a family history, genetic mutations or men in the black African or African American communities.
Back in the mid-2000s, Professor Emberton and others in the community wondered whether MRI could help in prostate cancer detection and started to informally ask men if they would undergo MRI as well as biopsy, to see if they were right. He says: “Prostate cancer was known as the invisible cancer: ultrasound did not help with diagnosis and physical examination often missed it. Although we were convinced MRI could work, I still remember the first time we observed it in a patient.
“The beauty about diagnostics is that you get the answer very quickly, unlike in treatment trials. Following a small study funded by Pelican Prostate Cancer, we set up a larger multicentre study which was funded by the NIHR HTA to see if MRI was better than the standard diagnosis using biopsy. We recruited quickly and had the answer quickly.”
PROMIS offered 576 men standard care as well as MRI in order to compare what each test found and establish the proportion who could safely avoid biopsy, and the proportion with clinically significant prostate cancer identified using imaging. The tests were done independently and blinded to avoid bias. Not only did the trial find that half of high-risk cancers were missed using the traditional biopsy, the results, published in The Lancet, showed that MRI successfully identified 93% of cancers.
Professor Emberton points out that: “The men on this trial were incredibly altruistic. Each one agreed to undergo all tests for the sake of others in the future rather than just one standard test. Without their consent we could not have transformed the diagnostic pathway of the world’s second commonest cancer in men.”
A follow on trial that changed practice
The PRECISION study followed, also supported by the NIHR through the NIHR Biomedical Research Centres in Birmingham and at University College London Hospitals (UCLH). In this trial, 500 men with suspected prostate cancer were randomised to either biopsy or MRI.
The results, published in New England Journal of Medicine, found that MRI is superior to biopsy. Additionally, in the MRI arm of the trial fewer men were biopsied because imaging ruled out cancer, where needed biopsies were more accurate, cancers were better characterised and there were fewer complications.
The research was led by Dr Veeru Kasivisvanathan, a Urology Specialist Registrar and BURST Chair at University College London and UCLH. After completing an NIHR Academic Clinical Fellowship, he was successfully awarded an NIHR Doctoral Research Fellowship. Dr Kasivisvanathan said: “In men who need to have investigation for prostate cancer for the first time, PRECISION shows that using an MRI to identify suspected cancer in the prostate and performing a prostate biopsy targeted to the MRI information, leads to more cancers being diagnosed than the standard way that we have been performing prostate biopsy for the last 25 years.”
He adds: “My NIHR award has enabled me to become an academic clinician and gain skills required to carry out multi-centre interventional studies that can change clinical practice.”
As a result of these two studies, the NICE recommended that all men at risk of prostate cancer receive an MRI scan ahead of a biopsy and the adoption of a diagnostic tool, combining the use of MRI scan and targeted biopsy, to undertake this.
Professor Emberton explains why the NIHR’s unique connection with the NHS is beneficial: “Other countries struggle to do imaging studies, but because we use the NHS as the engine we don’t have to pay additional costs for MRIs. Elsewhere in the world we would have to pay for every scan on top of the research cost. We can do these kinds of studies in the NHS cheaply and efficiently. PROMIS and PRECISION are the only two studies in this area and they were both done in our distinctive environment in the UK.”
Thanks to the work of Emberton, Kasivisvanathan and their collaborators, a quarter of men with suspected prostate cancer, over one million men each year, can now avoid an invasive biopsy. And with each biopsy costing approximately £600 of NHS expenditure the savings to the NHS and health services around the world are immense, before the long-term costs of managing overdiagnosis that can result from those unnecessary biopsies being done.
After the MRI, for those who do need biopsy there are fewer needle misses as clinicians know where the cancer is. They are able to obtain more representative histopathology with fewer biopsies, less harm, and at a reduced cost.