Tool can predict men at greatest risk of prostate cancer, say University of Cambridge and ICR researchers

A comprehensive tool for predicting an individual’s risk of developing prostate cancer has been created by scientists at the University of Cambridge and The Institute of Cancer Research, London.

They hope it will help ensure men at greatest risk receive the appropriate testing while reducing unnecessary and potentially invasive testing for those at very low risk.

CanRisk-Prostate will be incorporated into the team’s free CanRisk web tool, which is used by healthcare professionals worldwide and has made almost 1.2 million risk predictions for breast and ovarian cancers.

The most common type of cancer in men, with more than 52,000 diagnoses in the UK each year, it causes more than 12,000 deaths annually. While 78 per cent survive more than 10 years, the proportion has barely changed in the last decade.

Current tests involve a blood test to look for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland, but it is not always accurate. Three in four men with a raised PSA level will not have cancer, meaning further tests, such as tissue biopsies or MRI scans, are required to confirm a diagnosis.

Prof Antonis Antoniou, from the Department of Public Health and Primary Care at the University of Cambridge, said: “Prostate cancer is the most common cancer in men in the UK, but population-wide screening based on PSA isn’t an option: these tests are often falsely positive, which means that many men would then be biopsied unnecessarily. Also, many prostate tumours identified by PSA tests are slow-growing and would not have been life-threatening. The treatment of these tumours may do more harm than good.

“What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do.

“For the first time, it combines information on the genetic make-up and prostate cancer family history, the main risk factors for the disease, to provide personalised cancer risks.”

It is one of the most genetically determined of common cancers, with inherited faulty versions of the BRCA2, HOXB13 and possibly BRCA1 genes associated with moderate-to-high risk of prostate cancer, although such faults are rare in the population.

Several hundred more common genetic variants confer a lower risk, but together moderate or increase risk.

The researchers, supported by Cancer Research UK, created the first comprehensive prostate cancer model using genetic and cancer family history data from almost 17,000 families affected by the disease.

Data on rare genetic faults in moderate-to-high-risk genes and a risk score based on 268 common low-risk variants, along with detailed cancer family history, are used to predict the future risks.

While 16 per cent of men will develop prostate cancer by the time they are 85, the team found that the predicted risk was higher for men who had a father diagnosed with prostate cancer. It was 27 per cent if the father was diagnosed at 80, or 42 per cent if the father was diagnosed at 50.

And the risks were considerably higher for men with genetic faults, with 54 per cent of men carrying an alteration in the BRCA2 gene developing prostate cancer. Among men with BRCA2 gene faults, the risks were substantially lower, however, if they also had a small number of the low-risk variants, But they were much higher if they also had a large number of the low-risk variants.

Clinicians could use such information to provide a personalised risk.

The risk model was validated on an independent cohort of more than 170,000 men recruited to UK Biobank database, all of whom were free from prostate cancer when they were recruited. More than 7,600 developed prostate cancer within the subsequent 10 years and the researchers found 86 per cent of them were in the half of men with the highest predicted risks. That suggests it may be possible to target screening and diagnostic tests to the subgroup at highest risk.

Dr Tommy Nyberg, from the MRC Biostatistics Unit at Cambridge, said: “We’ve created the most comprehensive tool to date for predicting a man’s risk of developing prostate cancer. We hope this will help clinicians and genetic counsellors assess their clients’ risk and provide the appropriate follow-up.

“Over the next 12 months, we aim to build this tool into the widely used CanRisk tool, which will facilitate the risk-based clinical management of men seen in family cancer clinics and enable risk-adapted early detection approaches to the population at large.”

Co-author Prof Ros Eeles, from The Institute of Cancer Research, London, said: “This is an important step forward as it will enable clinicians to have conversations with men about their individual risk of prostate cancer based on the most accurate computer model to date. This will help them in making decisions about screening.”

The data used so far has been from men of European ancestry but the team hope include data from men of other ethnicities as further work is undertaken.

The research was supported by the Cancer Research UK-funded CanRisk programme. Additional support for CanRisk-Prostate was provided by Prostate Cancer UK, The Institute of Cancer Research, Everyman Campaign, National Cancer Research Network UK, National Cancer Research Institute, NIHR Cambridge Biomedical Research Centre and the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.