A four-kallikrein panel and β-microseminoprotein in predicting high-grade prostate cancer on biopsy: An independent replication from the Finnish section of the European Randomized Study of Screening for Prostate Cancer Journal Article


Authors: Assel, M.; Sjöblom, L.; Murtola, T. J.; Talala, K.; Kujala, P.; Stenman, U. H.; Taari, K.; Auvinen, A.; Vickers, A.; Visakorpi, T.; Tammela, T. L.; Lilja, H.
Article Title: A four-kallikrein panel and β-microseminoprotein in predicting high-grade prostate cancer on biopsy: An independent replication from the Finnish section of the European Randomized Study of Screening for Prostate Cancer
Abstract: Background: A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4KscoreTM. Objective: To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Design, setting, and participants: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls. Outcome measurements and statistical analysis: The predictive accuracy of prespecified prediction models was compared with biopsy outcomes. Results and limitations: Among men with PSA of 4.0–25 ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614–0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717–0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p = 0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0–3.99 ng/ml and the absence of digital rectal examination results. Conclusions: These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. Patient summary: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen. © 2017 European Association of Urology Four kallikrein markers and β-microseminoprotein (MSP) in blood improve discrimination of high-grade cancer at biopsy in men with elevated prostate-specific antigen. These kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. © 2017 European Association of Urology
Keywords: prostate cancer; screening; prediction models; beta-microseminoprotein; 4kscore; kallikriens
Journal Title: European Urology Focus
Volume: 5
Issue: 4
ISSN: 2405-4569
Publisher: Elsevier B.V.  
Date Published: 2019-07-01
Start Page: 561
End Page: 567
Language: English
DOI: 10.1016/j.euf.2017.11.002
PUBMED: 29137895
PROVIDER: scopus
PMCID: PMC5948115
DOI/URL:
Notes: Article -- Export Date: 1 October 2019 -- Source: Scopus
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  1. Hans Gosta Lilja
    345 Lilja
  2. Andrew J Vickers
    887 Vickers
  3. Melissa Jean Assel
    110 Assel