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Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men

Sjoberg, Daniel D.; Vickers, Andrew J.; Assel, Melissa; Dahlin, Anders LU ; Poon, Bing Ying; Ulmert, David LU and Lilja, Hans LU (2018) In European Urology 73(6). p.941-948
Abstract

Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Outcome measurements and statistical... (More)

Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Outcome measurements and statistical analysis: Prostate cancer death (n = 317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Results and limitations: Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0. ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6. ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. Conclusions: A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Patient summary: Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Kallikrein, Prostate-specific antigen, Screening
in
European Urology
volume
73
issue
6
pages
941 - 948
publisher
Elsevier
external identifiers
  • scopus:85042880169
  • pmid:29519548
ISSN
0302-2838
DOI
10.1016/j.eururo.2018.02.016
language
English
LU publication?
yes
id
eeae34f7-4d31-4f16-9b42-4df625bd5f08
date added to LUP
2018-03-27 10:24:38
date last changed
2019-07-16 03:46:27
@article{eeae34f7-4d31-4f16-9b42-4df625bd5f08,
  abstract     = {<p>Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Outcome measurements and statistical analysis: Prostate cancer death (n = 317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Results and limitations: Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0. ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of &lt;7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6. ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. Conclusions: A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Patient summary: Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy.</p>},
  author       = {Sjoberg, Daniel D. and Vickers, Andrew J. and Assel, Melissa and Dahlin, Anders and Poon, Bing Ying and Ulmert, David and Lilja, Hans},
  issn         = {0302-2838},
  keyword      = {Kallikrein,Prostate-specific antigen,Screening},
  language     = {eng},
  number       = {6},
  pages        = {941--948},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men},
  url          = {http://dx.doi.org/10.1016/j.eururo.2018.02.016},
  volume       = {73},
  year         = {2018},
}