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 Journal Article


Authors: Sjoberg, D. D.; Vickers, A. J.; Assel, M.; Dahlin, A.; Poon, B. Y.; Ulmert, D.; Lilja, H.
Article 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
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 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. © 2018 European Association of Urology
Keywords: adult; aged; unclassified drug; major clinical study; cancer risk; prostate specific antigen; cohort analysis; cancer mortality; age; prostate cancer; prostate-specific antigen; screening; prostate biopsy; kallikrein; observational study; statistical model; predictive value; enzyme blood level; low risk population; human; male; priority journal; article; human kallikrein related peptidase 2
Journal Title: European Urology
Volume: 73
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2018-06-01
Start Page: 941
End Page: 948
Language: English
DOI: 10.1016/j.eururo.2018.02.016
PROVIDER: scopus
PMCID: PMC5960423
PUBMED: 29519548
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja
  2. Andrew J Vickers
    565 Vickers
  3. Daniel D. Sjoberg
    141 Sjoberg
  4. Hans David Staffan Ulmert
    50 Ulmert
  5. Melissa Jean Assel
    39 Assel
  6. Jessica Bing Ying Poon
    15 Poon