Sophie Lutter explains the full story behind the 'extremely promising' results from a Swedish trial of a new prostate cancer screening programme and how Prostate Cancer UK plans to fund further trials in this country.

11 Nov 2015

Blood tests

Around-the-clock daylight (in summer at least), cutting-edge design and scenic cityscapes all make Stockholm an attractive place to live – if you can cope with herrings for breakfast or, you know, at all. But more importantly, the results of the STOCKHOLM-3 (S3M) trial, published in the journal Lancet Oncology this week, suggest that the hometown of Eurovision’s greatest ever competition entry might also be on the way to having the world’s first effective prostate cancer screening programme.

How the trial worked

Over 47,000 men between the ages of 50 and 69, who had not been diagnosed with prostate cancer, took part in the study. The researchers took a blood sample from all the men to do a Prostate Specific Antigen (PSA) test. This is the current best available test for prostate problems, but while it's a good indicator of prostate problems, it's not always a reliable indication of prostate cancer. This means that many men end up being referred for biopsies that they may not need, while other men with advanced prostate cancer slip through the net.

In standard UK clinical practice, a man would be referred to the urologist for further investigation if he had a PSA level of 3ng/ml or over (depending on his age and other risk factors). In this study, any blood samples that recorded a PSA level of 1ng/ml or more were then put through the S3M test panel. This is a panel of genetic and protein biomarkers that the researchers hoped would, when combined, give a reliable indication of the presence of clinically significant prostate cancer. Anyone who had a PSA level of 3ng/ml or more, or scored highly on the S3M panel, or both was considered to be at high risk of harmful prostate cancer was then referred to a urologist for a Digital Rectal Examination and prostate volume check. If abnormalities were found, the man went on to have a biopsy.

Trial design

Trial process

Trial results

The researchers found that the S3M test was much better than PSA alone at detecting potentially dangerous prostate cancers (those with a Gleason score of 7 or more), and every independent step of the assessment process – from risk assessment, through biomarker panel to prostate exam  added an extra level of prediction to the test.

This suggests that this risk assessment process has the potential to aid early diagnosis and stop men slipping through the net with dangerous prostate cancers.

One of the major criticisms against the PSA test, and the main reason it is not considered reliable enough to be used in a screening program, is that so many men end up undergoing the pain and discomfort of a biopsy – not to mention the attendant risk of septicemia and infection with antibiotic resistant bacteria – for either no cancer at all, or a form of prostate cancer that would never cause them harm.

In this trial, of 47,688 men who were screened, only 4,947 ended up being biopsied. This represents a 32 per cent drop in the total number of biopsies performed, compared to the number having a biopsy on the basis of a PSA level of 3ng/ml or more alone, as happens at the moment. This figure includes a 44 per cent drop in the number of negative biopsies performed.

Together, these results give compelling evidence that the S3M risk assessment model can dramatically reduce the number of men undergoing unnecessary biopsies, without compromising the safety of men who do have an aggressive form of prostate cancer.

The limitations

While these results are extremely promising, and undoubtedly represent a major step change in prostate cancer risk assessment, unfortunately it isn’t yet time to slap ourselves on the back for a job well done and head to the nearest pub.

This trial was only run in Stockholm, so the population group of men taking part in the study was quite narrow. It’s going to be important to validate this study in a more diverse population before we can accept that it will work elsewhere. For example, the UK has a multi-ethnic population, with men from diverse socio-economic backgrounds and with a wide range of other health conditions. We still need to work out whether the S3M test will work as well in such a diverse population.

In addition, all the biopsy results in this study were analysed by a single pathologist. This was important in the context of this research to reduce uncertainty and differences of opinion among experts when interpreting the results. But it isn’t very representative of a real-world situation. We need to know whether the test results would still be as consistent and impressive within a busy health service.

Finally, although the cost of genetic and biomarker tests are coming down all the time as the technology gets more advanced, we still don’t know exactly how much these tests will cost outside of a research setting and whether the added predictive benefit we get from including these tests is worth their price tag for the NHS.

The next steps

This is a potentially game-changing step forward for prostate cancer risk assessment so we want to make sure that UK men can benefit from this discovery. There’s still some work to do to make sure that these results will work in the UK. We’ve been working with the Swedish research team since December last year to understand how we can make this happen. We have a plan in place to fund research to validate these results in the UK and check that the differences between the UK population and NHS practice don’t affect how well this new model works. We’ll be announcing a funding scheme to address this in the next couple of months.

We do know that this research will take some time, and we believe that men need a better test of their risk as soon as possible. That’s why we’re also funding an international team of scientists to develop a risk assessment tool for use within primary care in the UK. These plans are still going full-steam ahead, and we expect to have more to say about this in the New Year. That work will accommodate this new Stockholm model when we’ve shown that it’s effective in the UK.

These two important areas of research funding are going to be absolutely key in enabling us to deliver the ‘better diagnosis’ strand of our ambitious new research strategy. We can now be confident that due to this research and the efforts of the researchers behind them, the future is looking brighter for men at risk of prostate cancer in the UK.

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