“This study reinforces the strength of Stockholm3,” says Professor of Urology and Epidemiology & Biostatistics Matthew Cooperberg, co-author and researcher at the University of California, San Francisco. “Stockholm3 identified men who would normally be missed by commonly used PSA thresholds. Without detection and treatment, the data suggest that many of these men would have faced a substantial risk of prostate cancer–related mortality.”

“This long-term analysis of the STHLM3 trial shows that the Stockholm3 blood test can identify aggressive prostate cancers that conventional PSA thresholds may miss, particularly among men with PSA below 3 ng/ml, who remain at notable risk of recurrence despite curative treatment. On the other hand, men with elevated PSA, but low Stockholm3 scores, had low recurrence rates, highlighting the potential of this biomarker in reducing unnecessary biopsies and overdiagnosis of indolent disease,” says Associate Editor, European Urology: Gianluca Giannarini, MD.

"This changes how we think about the selection of men for screening and treatment in clinical practice." says Tobias Nordström, Urologist and Associate Professor at the Karolinska Institute. “Specifically, it reinforces the benefits of using risk-prediction tools such as Stockholm3 for men with low PSA levels.”

The findings extend the landmark STHLM3 screening trial published in 2015 (1) with nine-year follow-up data. The study includes 968 men treated for prostate cancer with radical prostatectomy or radiotherapy after screening, evaluating biochemical recurrence (BCR) and high risk BCR (2).

Key Findings:

• Men flagged as high risk by Stockholm3 (Stockholm3 Risk Score ≥ 11) despite having a low PSA (PSA < 3 ng/mL) were about nine times more likely (HR: 8.8, 1.06-72, p: 0.04) to have a high-risk BCR after treatment than men flagged by PSA alone (PSA 3 ng/mL or higher but Stockholm3 Risk Score < 11).
• In contrast, when PSA was high (3 ng/mL or more), but the Stockholm3 was negative (Stockholm3 Risk Score <11), cancer rarely came back over the long term. That suggests the disease was more indolent and slow growing in those men.
• The 5-year high risk BCR rate was significantly different across groups (p<0.001):
  • 9.0% in men with both elevated PSA and Stockholm3,
  • 5.3% in men with elevated Stockholm3 only,
  • 0% in men with elevated PSA only and negative Stockholm3,
  • 0% in men with low PSA and negative Stockholm3.

A Paradigm Shift in Prostate Cancer Screening

Current clinical guidelines rely on PSA thresholds of ≥3–4 ng/mL in identifying candidates for biopsy and treatment. This study shows that relying on PSA alone risks missing aggressive cancers, particularly in men with low PSA values. Men with aggressive cancers in low PSA values also have a significantly higher risk of dying from the disease.

1. Grönberg, H et al. “Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study.” The Lancet. Oncology vol. 16,16 (2015): 1667-76. doi:10.1016/S1470-2045(15)00361-7
2. Vigneswaran, HT 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.” European urology, S0302-2838(25)04735-9. 16 Oct. 2025, doi:10.1016/j.eururo.2025.10.001