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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

Assel, Melissa; Sjöblom, Liisa; Murtola, Teemu J.; Talala, Kirsi; Kujala, Paula; Stenman, Ulf Håkan; Taari, Kimmo; Auvinen, Anssi; Vickers, Andrew and Visakorpi, Tapio, et al. (2017) In European Urology Focus
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 4Kscore™. 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... (More)

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 4Kscore™. 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. 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.

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4Kscore, Beta-microseminoprotein, Kallikriens, Prediction models, Prostate Cancer, Screening
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European Urology Focus
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Elsevier
external identifiers
  • scopus:85033587698
ISSN
2405-4569
DOI
10.1016/j.euf.2017.11.002
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English
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bd0bb799-df7c-4262-b826-938f582b20cd
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2017-12-01 13:37:25
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@article{bd0bb799-df7c-4262-b826-938f582b20cd,
  abstract     = {<p>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 4Kscore™. 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. 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.</p>},
  author       = {Assel, Melissa and Sjöblom, Liisa and Murtola, Teemu J. and Talala, Kirsi and Kujala, Paula and Stenman, Ulf Håkan and Taari, Kimmo and Auvinen, Anssi and Vickers, Andrew and Visakorpi, Tapio and Tammela, Teuvo L. and Lilja, Hans},
  issn         = {2405-4569},
  keyword      = {4Kscore,Beta-microseminoprotein,Kallikriens,Prediction models,Prostate Cancer,Screening},
  language     = {eng},
  month        = {11},
  publisher    = {Elsevier},
  series       = {European Urology Focus},
  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},
  url          = {http://dx.doi.org/10.1016/j.euf.2017.11.002},
  year         = {2017},
}