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The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy

Vickers, Andrew J.; Ulmert, David; Serio, Angel M.; Björk, Thomas LU ; Scardino, Peter T.; Eastham, James A.; Berglund, Göran LU and Lilja, Hans (2007) In International Journal of Cancer 121(10). p.2212-2217
Abstract
Both benign and malignant prostate diseases elevate total prostate-specific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that free-to-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age >= 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up... (More)
Both benign and malignant prostate diseases elevate total prostate-specific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that free-to-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age >= 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up to 1999 and in 1,292 matched controls. The predictive value of tPSA was lower in older men (p = 0.003) but was not strongly affected by time to diagnosis (p = 0.3); the predictive value of hK2 was higher closer to diagnosis (p < 0.0005) but was not modified by age (p = 0.7). A model including tPSA, fPSA and hK2 was superior (p = 0.02) to tPSA alone in older (AUC 0.819 vs. 0.794), but not in younger men (0.758 vs. 0.759). Total PSA can be used as a single marker at early middle age to predict long-term risk of prostate cancer and thus to determine intensity of subsequent screening. In contrast, %fPSA and hK2 add important predictive value in older men and much closer to diagnosis. Strategies for prostate cancer screening should be based on thorough understanding of the interaction of kallikreinrelated biomarkers with prostate pathobiology. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
detection, prostate cancer, prediction, prostate specific antigen
in
International Journal of Cancer
volume
121
issue
10
pages
2212 - 2217
publisher
John Wiley & Sons
external identifiers
  • wos:000250245100012
  • scopus:35348823195
ISSN
0020-7136
DOI
10.1002/ijc.22956
language
English
LU publication?
yes
id
adc0faaa-0a94-4172-bcab-bd83d0110996 (old id 654320)
date added to LUP
2007-12-19 09:29:36
date last changed
2017-09-03 03:46:25
@article{adc0faaa-0a94-4172-bcab-bd83d0110996,
  abstract     = {Both benign and malignant prostate diseases elevate total prostate-specific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that free-to-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age &gt;= 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up to 1999 and in 1,292 matched controls. The predictive value of tPSA was lower in older men (p = 0.003) but was not strongly affected by time to diagnosis (p = 0.3); the predictive value of hK2 was higher closer to diagnosis (p &lt; 0.0005) but was not modified by age (p = 0.7). A model including tPSA, fPSA and hK2 was superior (p = 0.02) to tPSA alone in older (AUC 0.819 vs. 0.794), but not in younger men (0.758 vs. 0.759). Total PSA can be used as a single marker at early middle age to predict long-term risk of prostate cancer and thus to determine intensity of subsequent screening. In contrast, %fPSA and hK2 add important predictive value in older men and much closer to diagnosis. Strategies for prostate cancer screening should be based on thorough understanding of the interaction of kallikreinrelated biomarkers with prostate pathobiology.},
  author       = {Vickers, Andrew J. and Ulmert, David and Serio, Angel M. and Björk, Thomas and Scardino, Peter T. and Eastham, James A. and Berglund, Göran and Lilja, Hans},
  issn         = {0020-7136},
  keyword      = {detection,prostate cancer,prediction,prostate specific antigen},
  language     = {eng},
  number       = {10},
  pages        = {2212--2217},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy},
  url          = {http://dx.doi.org/10.1002/ijc.22956},
  volume       = {121},
  year         = {2007},
}