Stockholm 3 a new blood test for prostate cancer risk

Stockholm3 – Detecting the Prostate Cancers that require treatment earlier.

Prostate cancer is the most common cancer in males. A man dies of the disease every 45 minutes in the UK, and one in eight men will be diagnosed in their lifetime. Two of the biggest challenges in diagnosing prostate cancer are early detection and over-treatment. Stockholm3 is a blood test that addresses these by assessing the risk of prostate cancer that requires treatment more accurately than current practice.

PSA and overtreatment/late detection

So far, men’s risk of developing Prostate Cancer has been assessed using a single protein marker called PSA. This has led to both overtreatment of prostate cancers that will never grow to cause any problems and detecting too late aggressive prostate cancers that do not raise the PSA levels. Between 30-50% of all aggressive cases of prostate cancer are missed by using PSA alone while 70-80% of Men with a raised PSA either do not have Cancer or have Prostate Cancer that is not aggressive and does not require treatment.

UK age-related PSA level cutoffs

 If your PSA test result is above these levels you are deemed to be higher risk and sent for further investigations and if it is below these cutoffs you are deemed to be low risk and no further investigation is recommended.

Overtreatment is where harm is caused to a man by treating or monitoring prostate cancers that will never grow to cause any harm in the man’s lifetime.

If you use a PSA “cutoff” that is too low to assess risk, you increase the number of Men you send for an unnecessary MRI/Biopsy leading to overtreatment. If you use a too-high PSA cutoff, you miss too many aggressive prostate cancers, leading to cancer being diagnosed too late. Whatever value you use there is always a trade-off between these two problems.

Biopsies should be avoided for Men who are at low risk of aggressive prostate cancer because they are invasive, unpleasant and carry an infection risk. Biopsies are the only way to determine whether Prostate Cancer is present and is likely to spread but should be reserved for men at an increased risk. For many men, detecting Prostate Cancer that is very unlikely to cause them harm in their lifetime is more harmful than not detecting it.

MRI is not always effective at distinguishing between indolent and aggressive cancers though some of the latest technical advances have improved this significantly. MRI is very effective at finding the location of abnormal areas which can be useful when targeting where biopsies samples are taken from the prostate. However, given that most men over 60 will have one or more prostate cancer lesions, it is better to have an accurate assessment of the risk of aggressive prostate cancer prior to MRI to avoid unnecessary biopsies and over-treatment.

Stockholm3 Biomarkers

The problem with using only a single biomarker like PSA is the same result can mean different levels of risk to different men. The age-related cutoffs can improve this slightly but the problem remains for example if someone has genetic risk factors that differ or have a family history of prostate cancer. Using more than one marker to assess risk helps to individualise the risk score.

Stockholm3 tests for 5 protein biomarkers –

1. Total Prostate Specific antigen (PSA)
2. Free or “unbound” PSA
3. PSP94 – Prostate Secretory Protein
4. Growth Differentiating Factor 15
5. Kallikrein–related peptidase 2 (KLK2 similar to PSA which is KLK3)

And also 101 genetic markers called single nucleotide polymorphisms (SNPs). These are small variations in codes for the same gene. This is different to detecting the presence of a specific gene.

Algorithm to detect risk more accurately.

Over 11 years of painstaking research have determined how the levels of these biomarkers contribute to the risk of aggressive prostate cancer specifically. The algorithm also adjusts these levels according to clinical information and this is also recorded when the man takes the test.

Clinical Information

• Age
• Father, Brother or Son incidence of prostate cancer
• Whether a previous prostate biopsy has taken place or not.

A more precise test

Early detection is key to the successful treatment of prostate cancer. Using PSA alone leads to 30-50% of all aggressive cases of prostate cancer being missed. Stockholm3 is able to identify the high-risk patients at PSA levels as low as 1.5ng/ml while also identifying the low-risk men at PSA levels as high as 20ng/ml. In this way, Stockholm3 can improve early detection while also reducing the problem of over-detection.

Evidence

The Stockholm3 test has been validated in over 75, 000 men and has been used in health systems in Sweden, Norway and Finland. The test has also recently been introduced in Germany, Switzerland and Turkey. Results have been published in international peer-reviewed journals and the National Institute of Clinical Excellence (NICE) have undertaken a thorough innovation medtech review of the product. https://www.nice.org.uk/advice/mib303 NICE have summarised that the evidence is adequate and of good methodological quality. They say that the evidence suggests that Stockholm3 is more effective at predicting risk than PSA testing alone for men aged 45-74 with PSA of at least 1.5ng/ml.

Test result

The result from Stockholm3 is a risk score that indicates the risk of aggressive prostate cancer in the form of a traffic light.

• Green light indicates a low risk – the recommendation is to be tested again in 6 years
• Yellow Light indicates Normal Risk – the recommendation is to be tested again in 2 years
• Red Light indicates elevated risk – referral to a Urologist is recommended for MRI/Biopsy

References and further information