Advice
The technology
The technology
Stockholm3 (A3P Biomedical AB) is a blood-based diagnostic test that is to be used alongside prostate-specific antigen (PSA) testing to predict risk of prostate cancer in people aged 45 to 74 years with no previous prostate cancer diagnosis. The technology uses an algorithm that combines plasma protein biomarkers, genetic markers, and clinical data and would be used in people with a PSA of at least 1.5 nanograms per ml. It uses 5 plasma protein markers (human glandular kallikrein 2 [hK2], microseminoprotein beta [MSMB], microphage inhibitory cytokine-1 [MIC1], total PSA and free PSA). The genetic markers include 101 single nucleotide polymorphisms. The clinical data captured in the algorithm includes age, family history and previous prostate biopsy. Stockholm3 gives a score that indicates the risk of prostate cancer. A Stockholm3 risk score of at least 11% is considered an indicator of prostate cancer risk, and if it is used in primary care, these people would be referred to a hospital for an MRI.
Innovations
The company claims that using Stockholm3 may improve diagnostic accuracy and reduce unnecessary MRIs and biopsies. The technology can predict the risk of prostate cancer in people with low PSA levels (at least 1.5 nanograms per ml) and increase the sensitivity to identify prostate cancer compared with age-specific PSA levels.
Current care pathway
The UK National Screening Committee does not currently recommend screening for prostate cancer. This is because the PSA test is not accurate enough to detect prostate cancer that needs treatment, there is a lack of treatment that is definitely better for people with early-stage prostate cancer, and the potential harm from PSA-based screening programmes.
PSA testing in the UK is only recommended in people suspected of having prostate cancer. Possible symptoms of prostate cancer include any lower urinary tract symptoms (nocturia, urinary frequency, hesitancy, urgency or retention) or erectile dysfunction. People with suspected prostate cancer based on the above symptoms are offered a blood test to check PSA levels and digital rectal exam (DRE). This is 1 of the points in the pathway where Stockholm3 is proposed by the company to be used, alongside the PSA test.
After the PSA tests and DRE (if done), some people may be referred to a urologist in secondary care where NICE's guideline on prostate cancer: diagnosis and management recommends offering multi-parametric MRI, with results reported using 1 of the 5-point scales (Prostate Imaging Reporting and Data System [PI-RADS] or the Likert scale). The company say Stockholm3 could be used as the first stage of testing in secondary care instead of MRI, meaning some people could avoid the need for MRI or biopsy. Urologists will currently consider if a biopsy is appropriate depending on the results of the MRI. People whose MRI score is 1 or 2 may opt in or out for a systematic prostate biopsy after discussing the risk-benefit ratio of the procedure with a healthcare professional. Individuals with a score of 3 or more should be offered a prostate biopsy. The prostate biopsy is done by a urologist. The tissue specimen from the biopsy is evaluated by a pathologist and scored according to the Gleason grading system. If it is Gleason grade 2 or more, the person is said to have clinically significant prostate cancer.
The NHS rapid diagnostic and research pathways handbook for implementing a timed prostate cancer diagnostic pathway set out that, if appropriate, a prostate biopsy should be done within 9 days from GP referral and a target of 5 days turnaround for reported pathology should be agreed as a minimum standard. This is a 14‑day turnaround from GP referral to prostate biopsy result. Many services adhere to The Royal College of Pathology's (RCP) key assurance indicators for laboratories. According to Prostate Cancer UK's best practice pathway, the diagnostic pathway can take up to 28 days before a definitive diagnosis is made. There is an acknowledged capacity challenge in the area with an increasing complexity and volume of pathology requests but with a lack of pathologists (see The Royal College of Pathologists report, Meeting pathology demand – Histopathology workforce census 2017/18).
The following publications have been identified as relevant to this care pathway:
Population, setting and intended user
According to the company, the technology is intended to help diagnose prostate cancer in people aged 45 to 74 years with no previous prostate cancer diagnosis and PSA of at least 1.5 nanograms per ml. Stockholm3 is intended to be used in addition to current methods of assessing PSA levels when testing for prostate cancer in primary care, where the same blood sample would be used if the PSA level is at least 1.5 nanograms per ml. It could alternatively be done by a urologist in a secondary care setting for people who would otherwise have an MRI. A clinical report is generated and sent to the doctor. The report includes a risk score that provides a recommendation on managing the condition for example, 'low risk of prostate cancer, new test recommended in 6 years' or 'increased risk for prostate cancer, referral to urologist is recommended'. A biopsy is recommended if prostate volume is less than 56 cubic centimetres or prostate DRE is abnormal. Otherwise, follow-up testing is recommended within 2 years.
Costs
Technology costs
The company states that the list price of Stockholm3 is £350 and that volume discounts are applicable. The company notes that their technology is more expensive than the PSA test alone, but claims it saves costs by reducing unnecessary MRIs and biopsies. The cost of £350 includes the analysis of the blood test. The total costs of delivering and implementing Stockholm3 will vary depending on the care setting and treatment pathway. Some additional costs such as for phlebotomy (£4; DAPS08), and collection and transport of the samples to the reference laboratory may already be captured in standard care costs.
Costs of standard care
Based on the Personal Social Services Research Unit (PSSRU) 2021, the cost of a DRE is £40 (GP appointment), and PSA testing in primary care is £27.75 (PSA test kit £8.75 plus nurse appointment £19). According to the national schedule of NHS reference costs 2019/20, a transrectal ultrasound-guided biopsy of prostate (LB76Z) costs £489 and a transperineal template biopsy of prostate (LB77Z) costs £1,477. A prostate multi-parametric MRI costs £273 (RD03Z). Cost of staff time and equipment needed to collect a blood sample is £4 (DAPS08, phlebotomy).
Resource consequences
The technology is currently not used in the NHS. It would be an addition to standard of care in the primary and secondary care setting. It would typically cost more than standard care but may result in improved outcomes because of improved sensitivity and specificity. This may result in earlier or more accurate diagnosis. The company claims that more accurate diagnosis may reduce overall patient mortality and would improve disease management or coordination of care and improve efficiencies within the NHS. The company states that adopting Stockholm3 for diagnosing prostate cancer could avoid unnecessary biopsies and reduce travel time. Summarised cost-utility evidence reports cost reductions of 17% and 23% to 28% because of reduced unnecessary MRIs, sepsis, and biopsies.