Stockholm3
Clinical Development in the United States

Stockholm3 is an investigational in vitro diagnostic test under clinical evaluation in the United States for potential use in prostate cancer screening to identify men at risk of aggressive (Grade Group ≥2) prostate cancer. Stockholm3 has not been cleared or approved by the U.S. Food and Drug Administration.

Prostate cancer

Prostate cancer is a major cause of cancer-related death.[1]

Early-stage disease is typically associated with good outcomes after treatment. Data from Surveillance, Epidemiology, and End Results (SEER) shows that men with prostate cancer detected at an early stage have an approximately 100% five-year survival rate, whereas those diagnosed at a late stage have a five-year survival of approximately 32%.[2]

For many years, early detection has relied on the prostate-specific antigen (PSA) blood test.[3, 4]

PSA-based screening has improved early detection of prostate cancer but has recognized limitations. PSA has limited ability to distinguish between slow-growing, harmless cancers and aggressive cancers that require treatment.[5]

PSA often rises for reasons unrelated to cancer, leading to many false alarms. These false positive test results can cause unnecessary biopsies and associated downstream harms, anxiety, and healthcare costs. These false alarms have been the focus of innovation with MRI and other methods. However, a major long-standing problem with PSA is that it misses aggressive cancers in men with low PSA levels, below commonly used cut-offs (3 ng/ml or 4 ng/ml). Up to 50% of aggressive prostate cancers occur at these low PSA levels, and some of these cancers may be more deadly than cancers found at higher PSA levels. [6-13]  

Screening for prostate cancer with PSA

Screening for prostate cancer with Stockholm3

Stockholm3 is a blood-based test that integrates protein biomarkers, genetic risk profiling, and clinical data to assess a man’s risk of harboring aggressive prostate cancer. 

Stockholm3 has been evaluated in prospective and population-based screening studies with a total of more than 90,000 men.

In a European screening cohort (N=12,670), Stockholm3 has showed 90% sensitivity and 89% specificity for detecting aggressive prostate cancer (Grade Group ≥2 cancer). PSA ≥3 ng/ml showed 74% sensitivity and 90% specificity, while PSA ≥4 ng/ml showed 52% sensitivity and 95% specificity in the same cohort.[15, 16]

In men with PSA ≥1.5 ng/mL, Stockholm3 has been shown to enable detection of aggressive cancers while reducing unnecessary biopsies in men with elevated PSA levels compared to PSA-based referral pathways.[15-18]

Long-term follow-up from the population-based European STHLM3 screening study suggests that cancers identified at low PSA levels but with elevated Stockholm3 scores may be biologically aggressive and clinically meaningful. Men diagnosed under these conditions had an approximately ninefold higher risk of high-risk biochemical recurrence (an indicator of progression to metastatic and potentially lethal disease) after curative treatment compared with men with higher PSA but low Stockholm3 risk (HR 8.8; 95% CI: 1.06–72).[14] 

Real-world use studies in Northern Europe have reported stage migration and increased detection of aggressive prostate cancer following replacement of PSA-based screening strategies. 

  • Compared with national Swedish registry data, a stage migration at biopsy was observed for the cancers detected at the Capio Prostate Cancer Center (N=12,405) which showed 46% fewer low-risk diagnoses, a higher proportion (+41%) of intermediate-risk cancers, and 19% fewer high risk, advanced and metastatic cancers.[18]

  • In a cross-sectional, population-based health-system implementation study in Norway (N=4,784), replacement of PSA with Stockholm3 was associated with an 89% relative increase in detection of aggressive prostate cancer and a 26% reduction in detection of Grade Group 1 disease compared to the prior PSA-based pathway.[17]

Studies have also shown that Stockholm3 performs similarly across racial and ethnic groups, including White, Black, Hispanic and Asian men.[19]

All results are derived from peer-reviewed publications.

Important Regulatory Notice

Stockholm3 is investigational in the United States. Performance data presented here are derived from published studies conducted outside the U.S. and from North American cohorts.

The device is not cleared or approved by the U.S. Food and Drug Administration.

  • References

    1. James, N.D., I. Tannock, J. N'Dow, F. Feng, S. Gillessen, S.A. Ali, et al., The Lancet Commission on prostate cancer: planning for the surge in cases. Lancet, 2024. 403(10437): p. 1683-1722.

    2.  Mali, B., A. Mali, A. Mali, M. Abdulrazzak, and A.W.M. Jobran, Exploring the Epidemiological Characteristics and Survival Analysis Among Prostate Cancer Patients Under 50: A Seer-Based Population Study. Health Sci Rep, 2025. 8(1): p. e70414.

    3. Wolf, A.M., R.C. Wender, R.B. Etzioni, I.M. Thompson, A.V. D'Amico, R.J. Volk, et al., American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin, 2010. 60(2): p. 70-98.

    4. U.S.P.S.T.F., D.C. Grossman, S.J. Curry, D.K. Owens, K. Bibbins-Domingo, A.B. Caughey, et al., Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 2018. 319(18): p. 1901-1913.

    5. Loeb, S., M.A. Bjurlin, J. Nicholson, T.L. Tammela, D.F. Penson, H.B. Carter, et al., Overdiagnosis and overtreatment of prostate cancer. Eur Urol, 2014. 65(6): p. 1046-55.

    6. Thompson, I.M., D.K. Pauler, P.J. Goodman, C.M. Tangen, M.S. Lucia, H.L. Parnes, et al., Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med, 2004. 350(22): p. 2239-46.

    7. Andriole, G.L., D.L. Levin, E.D. Crawford, E.P. Gelmann, P.F. Pinsky, D. Chia, et al., Prostate Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of a randomized trial. J Natl Cancer Inst, 2005. 97(6): p. 433-8.

    8. Mahal, B.A., A.A. Aizer, J.A. Efstathiou, and P.L. Nguyen, Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer. Cancer, 2016. 122(1): p. 78-83.

    9. Eldred-Evans, D., H. Tam, H. Sokhi, A.R. Padhani, M. Connor, D. Price, et al., An Evaluation of Screening Pathways Using a Combination of Magnetic Resonance Imaging and Prostate-specific Antigen: Results from the IP1-PROSTAGRAM Study. Eur Urol Oncol, 2023. 6(3): p. 295-302.

    10. Fankhauser, C.D., M.G. Parry, A. Ali, T.E. Cowling, J. Nossiter, A. Sujenthiran, et al., A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer. Eur J Cancer, 2023. 181: p. 70-78.

    11. Moller, F., M. Mansson, J. Wallstrom, M. Hellstrom, J. Hugosson, and R. Arnsrud Godtman, Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Goteborg-2 Prostate Cancer Screening Trial. Eur Urol, 2024.

    12. Chakraborty, G., N. Zaman, A.M. Pedraza, N. Kyprianou, and A.K. Tewari, Molecular insights of low-PSA–expressing high-risk prostate cancer. Journal of Clinical Oncology, 2025. 43(5_suppl): p. 416-416.

    13. McHugh, J.K., E.K. Bancroft, E. Saunders, M.N. Brook, E. McGrowder, S. Wakerell, et al., Assessment of a Polygenic Risk Score in Screening for Prostate Cancer. N Engl J Med, 2025. 392(14): p. 1406-1417.

    14. Vigneswaran, H.T., T. Palsdottir, C. Micoli, D. Tilki, D. Lin, M. Cooperberg, et al., Stockholm3 Versus Prostate-specific Antigen in Prostate Cancer Screening: 9-year Outcomes Demonstrating Improved Detection of Aggressive Cancers and Reduced Overdiagnosis from the STHLM3 Trial. Eur Urol, 2026. 89(1): p. 82-90.

    15. Nordstrom, T., A. Discacciati, M. Bergman, M. Clements, M. Aly, M. Annerstedt, et al., 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. 22(9): p. 1240-1249.

    16. Palsdottir, T., C. Micoli, M. Eklund, H. Gronberg, F. Jäderling, D. Tilki, et al. Stockholm3-MRI population-based screening: Two-year outcomes comparing Stockholm3 and PSA. ASCO Genitourinary Cancers Symposium. San Francisco, January 26-28, 2026. Journal of Clinical Oncology. Volume 44, Number 7_suppl.

    17. Viste, E., C.A. Vinje, T.G. Lid, S. Skeie, O. Evjen-Olsen, T. Nordstrom, et al., Effects of replacing PSA with Stockholm3 for diagnosis of clinically significant prostate cancer in a healthcare system - the Stavanger experience. Scand J Prim Health Care, 2020. 38(3): p. 315-322.

    18. Palsdottir, T., H. Soderback, F. Jaderling, M. Bergman, H. Vigneswaran, and H. Gronberg, The Capio Prostate Cancer Center Model for Prostate Cancer Diagnostics-Real-world Evidence from 2018 to 2022. Eur Urol Open Sci, 2024. 61: p. 29-36.

    19.  Vigneswaran, H.T., M. Eklund, A. Discacciati, T. Nordstrom, R.A. Hubbard, N. Perlis, et al., Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial. J Clin Oncol, 2024: p. JCO2400152.