The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy Journal Article
| Authors: | Vickers, A. J.; Ulmert, D.; Serio, A. M.; Björk, T.; Scardino, P. T.; Eastham, J. A.; Berglund, G.; Lilja, H. |
| Article Title: | The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy |
| 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 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 kallikrein-related biomarkers with prostate pathobiology. © 2007 Wiley-Liss, Inc. |
| Keywords: | adult; middle aged; unclassified drug; major clinical study; cancer risk; biological marker; prostate specific antigen; cancer screening; mass screening; prediction; time factors; age; prostate cancer; sweden; prostate-specific antigen; prostatic neoplasms; diagnostic value; early diagnosis; antigen detection; kallikrein; detection; age distribution; onset age; predictive value; tissue kallikreins; kallikrein 2; free to total prostate specific antigen ratio |
| Journal Title: | International Journal of Cancer |
| Volume: | 121 |
| Issue: | 10 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2007-11-15 |
| Start Page: | 2212 |
| End Page: | 2217 |
| Language: | English |
| DOI: | 10.1002/ijc.22956 |
| PUBMED: | 17657743 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 17 November 2011" - "CODEN: IJCNA" - "Source: Scopus" |
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