4Kscore as a Pre-MRI Reflex Test for Men with PSA 1.80–2.99 ng/ml in the Göteborg-2 Prostate Cancer Screening Trial
8 affiliations
- 1Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Skaraborg Skövde Hospital, Region Västra Götaland, Skövde, Sweden; Corresponding author. Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Tel. +46 70 558 7054.
- 2Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden; Department of Urology and Andrology, Institute of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden
- 3Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- 4Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Heidelberg, Germany; Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden
- 5Departments of Pathology and Laboratory Medicine, Surgery (Urology), and Medicine (GU-Oncology), Memorial Sloan Kettering Cancer Center, New York, USA; Department of Translational Medicine, Lund University, Malmö, Sweden
- 6Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
- 7Department of Radiology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Radiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
- 8Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
Abstract
Background: Lowering the prostate-specific antigen (PSA) cut-off from 3.0 to 1.8 ng/ml in prostate cancer (PCa) screening would improve diagnostic yield but substantially increase the number of men undergoing diagnostic work-up. Objective: To evaluate 4Kscore as a reflex test for pre-magnetic resonance imaging (MRI) risk stratification among men with PSA 1.80–2.99 ng/ml. Design, setting, and participants: This diagnostic biomarker study was nested within the population-based Göteborg-2 PCa screening trial and included men with PSA ≥1.80 ng/ml who were referred for MRI and provided blood for biomarker research, followed by targeted biopsy if MRI-positive (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The analysis included 555 men (median age 59 yr) with PSA 1.80–2.99 ng/ml, pre-MRI 4Kscore, and assessable MRI. Outcome measurements and statistical analysis: The primary outcome was International Society of Urological Pathology (ISUP) grade ≥2. Diagnostic performance of 4Kscore as a pre-MRI reflex test was assessed using sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUC), with 95% confidence intervals (CI). Results and limitations: MRI was positive in 116/555 men (21%). Overall, PCa was detected in 52/555 men (9.3%), including 27/555 men (4.9%) with ISUP grade ≥2. A 4Kscore ≥7.5% would detect 56% of the ISUP grade ≥2 cancers and reduce detection of ISUP grade 1 by 64%. This approach would reduce MRI referrals by 71% and referrals to biopsy by 67% compared with performing MRI in all men with PSA ≥1.80 ng/ml and performing biopsies in all men with suspected lesions. With a 4Kscore cut-off of 7.5%, sensitivity and specificity for detecting ISUP grade ≥2 were 56% (95% CI = 35–74) and 72% (95% CI = 68–76), respectively. The AUC was 0.69 (95% CI = 0.58–0.79). The limited number of clinically significant PCa cases restricts generalizability. Conclusions: Using a 4Kscore 7.5% cut-off as a reflex test before MRI in men with PSA 1.80–2.99 ng/ml could substantially reduce referrals to MRI and biopsy, reduce ISUP grade 1 cancer detection, and enable earlier detection of about half of ISUP grade ≥2 cancers. Many men with ISUP grade ≥2 cancers had 4Kscores <7.5%, and most men selected for MRI had PI-RADS <3. Evaluation of lower 4Kscore cut-offs, longer follow-up, and larger prospective studies is required before clinical implementation.
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BibTeX
@article{moller20264kscore,
title = {{4Kscore as a Pre-MRI Reflex Test for Men with PSA 1.80–2.99 ng/ml in the Göteborg-2 Prostate Cancer Screening Trial}},
author = {Fredrik Möller and Andreas Josefsson and Marianne Månsson and Sigrid Carlsson and Hans Lilja and Vasiliki Spyratou and Jonas Wallström and Jonas Hugosson and Rebecka Arnsrud Godtman},
journal = {European Urology Open Science},
year = {2026},
month = oct,
doi = {10.1016/j.euros.2026.10.001},
url = {https://doi.org/10.1016/j.euros.2026.10.001},
note = {CC BY},
}
RIS
TY - JOUR
TI - 4Kscore as a Pre-MRI Reflex Test for Men with PSA 1.80–2.99 ng/ml in the Göteborg-2 Prostate Cancer Screening Trial
AU - Fredrik Möller
AU - Andreas Josefsson
AU - Marianne Månsson
AU - Sigrid Carlsson
AU - Hans Lilja
AU - Vasiliki Spyratou
AU - Jonas Wallström
AU - Jonas Hugosson
AU - Rebecka Arnsrud Godtman
PY - 2026
DA - 2026/10/22
JO - European Urology Open Science
DO - 10.1016/j.euros.2026.10.001
UR - https://doi.org/10.1016/j.euros.2026.10.001
AB - Background: Lowering the prostate-specific antigen (PSA) cut-off from 3.0 to 1.8 ng/ml in prostate cancer (PCa) screening would improve diagnostic yield but substantially increase the number of men undergoing diagnostic work-up. Objective: To evaluate 4Kscore as a reflex test for pre-magnetic resonance imaging (MRI) risk stratification among men with PSA 1.80–2.99 ng/ml. Design, setting, and participants: This diagnostic biomarker study was nested within the population-based Göteborg-2 PCa screening trial and included men with PSA ≥1.80 ng/ml who were referred for MRI and provided blood for biomarker research, followed by targeted biopsy if MRI-positive (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The analysis included 555 men (median age 59 yr) with PSA 1.80–2.99 ng/ml, pre-MRI 4Kscore, and assessable MRI. Outcome measurements and statistical analysis: The primary outcome was International Society of Urological Pathology (ISUP) grade ≥2. Diagnostic performance of 4Kscore as a pre-MRI reflex test was assessed using sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUC), with 95% confidence intervals (CI). Results and limitations: MRI was positive in 116/555 men (21%). Overall, PCa was detected in 52/555 men (9.3%), including 27/555 men (4.9%) with ISUP grade ≥2. A 4Kscore ≥7.5% would detect 56% of the ISUP grade ≥2 cancers and reduce detection of ISUP grade 1 by 64%. This approach would reduce MRI referrals by 71% and referrals to biopsy by 67% compared with performing MRI in all men with PSA ≥1.80 ng/ml and performing biopsies in all men with suspected lesions. With a 4Kscore cut-off of 7.5%, sensitivity and specificity for detecting ISUP grade ≥2 were 56% (95% CI = 35–74) and 72% (95% CI = 68–76), respectively. The AUC was 0.69 (95% CI = 0.58–0.79). The limited number of clinically significant PCa cases restricts generalizability. Conclusions: Using a 4Kscore 7.5% cut-off as a reflex test before MRI in men with PSA 1.80–2.99 ng/ml could substantially reduce referrals to MRI and biopsy, reduce ISUP grade 1 cancer detection, and enable earlier detection of about half of ISUP grade ≥2 cancers. Many men with ISUP grade ≥2 cancers had 4Kscores <7.5%, and most men selected for MRI had PI-RADS <3. Evaluation of lower 4Kscore cut-offs, longer follow-up, and larger prospective studies is required before clinical implementation.
SN - 2666-1683
SN - 2666-1691
ER -