{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department 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.",
    "Department 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",
    "Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden",
    "Division 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",
    "Departments 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",
    "Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden",
    "Department of Radiology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Radiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden",
    "Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
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        0
      ],
      "name": "Fredrik Möller"
    },
    {
      "affs": [
        1
      ],
      "name": "Andreas Josefsson"
    },
    {
      "affs": [
        2
      ],
      "name": "Marianne Månsson"
    },
    {
      "affs": [
        3
      ],
      "name": "Sigrid Carlsson"
    },
    {
      "affs": [
        4
      ],
      "name": "Hans Lilja"
    },
    {
      "affs": [
        5
      ],
      "name": "Vasiliki Spyratou"
    },
    {
      "affs": [
        6
      ],
      "name": "Jonas Wallström"
    },
    {
      "affs": [
        7
      ],
      "name": "Jonas Hugosson"
    },
    {
      "affs": [
        7
      ],
      "name": "Rebecka Arnsrud Godtman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f8mfrj0r0xmmz.bib",
  "cited_by": 0,
  "doi": "10.1016/j.euros.2026.10.001",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2666168326033525",
  "id": "f8mfrj0r0xmmz",
  "issns": [
    "2666-1683",
    "2666-1691"
  ],
  "landing_url": "https://doi.org/10.1016/j.euros.2026.10.001",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Prostate Cancer"
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      "lcc",
      "RC254-282"
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      "lcc",
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      "2740|Prostate Cancer Diagnosis and Treatment"
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  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718394/pdf/?tool=EBI",
  "pmcid": "PMC13718394",
  "pmid": "42960148",
  "published": "2026-10-22",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/f8mfrj0r0xmmz.ris",
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  "subjects": [
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      "field": "medicine",
      "origin": "lcc:RC254-282",
      "subfield": "oncology"
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  ],
  "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",
  "title_text": "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",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:25Z",
  "url": "https://research.draconitic.com/paper/f8mfrj0r0xmmz",
  "venue": "European Urology Open Science",
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