Stockholm 3 test and prostate cancer

The Stockholm3 test predicts a man’s risk of having csPCa(clinically significant prostate cancer) in biopsy, based on a combination of plasma protein biomarkers (PSA, free PSA, hK2, MSMB, and MIC1), genetic markers, and clinical information (age, family history, prostate volume, and previous prostate biopsy):

• 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
• 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
• 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 (1)
    
• the STHLM3-MRI trial found that combining the Stockholm3 (STHLM3) blood test reduced the number of biopsies needed while still accurately detecting clinically significant prostate cancer compared to traditional methods using only prostate-specific antigen (PSA) and systematic biopsies (2)
  • compared with a PSA level of 3 nanograms per ml or higher, a Stockholm3 of 0.15 or higher provided identical sensitivity to detect clinically significant cancer and led to fewer MRI procedures (545 versus 846; 0.64) and fewer biopsy procedures (311 versus 338; 0.92)
  • compared with screening using PSA and systematic biopsies, a Stockholm3 of 0.11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3.0%] people tested versus 106 [2.1%] people tested, lower detection of low-grade cancers (50 [0.7%] versus 73 [1.4%]), and led to fewer biopsy procedures.
  • the study authors stated that he Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening
    • combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer
      
• a study assessed the economic impact of using the Stockholm3 test in European health care systems using real-world evidence for diagnostic outcomes and relevant costs (3)
  • found that combining prostate-specific antigen (PSA) measurement with the Stockholm3 test in identifying candidates for magnetic resonance imaging in prostate cancer management could significantly reduce health care costs
  • combined strategy outperformed the traditional PSA diagnostic approach
  • cost reduction is primarily because of a decrease in costs related to metastatic prostate cancer

Reference:

1. NICE (August 2022). Stockholm3 for prostate cancer screening.
2. Nordström Tet al, STHLM3 study group. Prostate cancer screening using a combination of risk-prediction, MRI, and targeted prostate biopsies (STHLM3-MRI): a prospective, population-based, randomised, open-label, non-inferiority trial. Lancet Oncol. 2021 Sep;22(9):1240-1249.
3. McLeod OD et al. Cost Analysis of Prostate Cancer Care Using a Biomarker-enhanced Diagnostic Strategy with Stockholm3.. Eur Urol Open Sci. 2024 Jun 25;66:26-32.