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Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated prostate‐specific antigen
Authors:Andrew J. Vickers PhD  Angel M. Cronin MS  Gunnar Aus MD  PhD  Carl‐Gustav Pihl MD  Charlotte Becker MD  PhD  Kim Pettersson PhD  Peter T. Scardino MD  Jonas Hugosson MD  PhD  Hans Lilja MD  PhD
Affiliation:1. Department of Epidemiology and Biostatistics, Memorial Sloan‐Kettering Cancer Center, New York, New YorkFax: (646) 735‐0011;2. Department of Epidemiology and Biostatistics, Memorial Sloan‐Kettering Cancer Center, New York, New York;3. Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden;4. Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden;5. Department of Laboratory Medicine, Lund University, University Hospital, Malmo, Sweden;6. Department of Biotechnology, University of Turku, Turku, Finland;7. Department of Surgery, Memorial Sloan‐Kettering Cancer Center, New York, New York;8. Department of Clinical Laboratories, Memorial Sloan‐Kettering Cancer Center, New York, New York;9. Department of Urology, Memorial Sloan‐Kettering Cancer Center, New York, New York;10. Department of Medicine, Lund University, University Hospital, Malmo, Sweden
Abstract:

BACKGROUND:

Risk models to predict prostate cancer on biopsy, whether they include only prostate‐specific antigen (PSA) or other markers, are intended for use in all men of screening age. However, the association between PSA and cancer probably depends on a man's recent screening history.

METHODS:

The authors examined the effect of prior screening on the ability to predict the risk of prostate cancer by using a previously reported, 4‐kallikrein panel that included total PSA, free PSA, intact PSA, and human kallikrein‐related peptidase 2 (hK2). The study cohort comprised 1241 men in Gothenburg, Sweden who underwent biopsy for elevated PSA during their second or later visit for the European Randomized Study of Screening for Prostate Cancer. The predictive accuracy of the 4‐kallikrein panel was calculated.

RESULTS:

Total PSA was not predictive of prostate cancer. The previously published 4‐kallikrein model increased predictive accuracy compared with total PSA and age alone (area under the curve [AUC], 0.66 vs 0.51; P < .001) but was poorly calibrated and missed many cancers. A model that was developed with recently screened men provided important improvements in discrimination (AUC, 0.67 vs 0.56; P < .001). Using this model reduced the number of biopsies by 413 per 1000 men with elevated PSA, missed 60 of 216 low‐grade cancers (Gleason score ≤6), but missed only 1 of 43 high‐grade cancers.

CONCLUSIONS:

Previous participation in PSA screening dramatically changed the performance of statistical models that were designed to predict biopsy outcome. A 4‐kallikrein panel was able to predict prostate cancer in men who had a recent screening history and provided independent confirmation that multiple kallikrein forms contribute important diagnostic information for men with elevated PSA. Cancer 2010. © 2010 American Cancer Society.
Keywords:prostate cancer  screening  prostate specific antigen  kallikreins  molecular markers
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