A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy

Research output: Contribution to journalArticle


Background: A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. Methods: The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution between 2002 and 2010. Adverse surgical pathology and biochemical recurrence (BCR) were pre-specified to be assessed in all men, biopsy GG 3 + 3, and 3 + 4. Results: Adjusted for established clinical predictors, the 4Kscore was significantly associated with adverse pathology (OR 1.49; 95% CI 1.32, 1.67; p < 0.0001). Adding 4Kscore increased discrimination from (AUC) 0.672 to 0.718 and 0.644 to 0.659 within biopsy GG 3 + 3 and 3 + 4, respectively. Higher 4Kscore was associated with higher risk of BCR (HR 1.16, 95% CI 1.06, 1.26; p = 0.001). Adding 4Kscore improved the prediction of BCR (C-index 0.630–0.660) within GG 3 + 3, but not GG 3 + 4. Conclusions: The 4Kscore can help guide the clinical decision whether additional risk assessment—such as confirmatory biopsy—is needed to decide between active surveillance versus curative therapy. Evidence that the panel could influence management in biopsy GG 3 + 4 is less strong and requires further investigation.


  • Alexander Haese
  • Amy L. Tin
  • Sigrid V. Carlsson
  • Daniel D. Sjoberg
  • Dirk Pehrke
  • Thomas Steuber
  • Hartwig Huland
  • Markus Graefen
  • Peter T. Scardino
  • Thorsten Schlomm
  • Andrew J. Vickers
  • Hans Lilja
  • Guido Sauter
External organisations
  • University Medical Center Hamburg-Eppendorf
  • Memorial Sloan-Kettering Cancer Center
  • Charité - University Medicine Berlin
  • University of Oxford
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
JournalBritish Journal of Cancer
Publication statusE-pub ahead of print - 2020 May 29
Publication categoryResearch