Prostate specific antigen for early detection of prostate cancer: longitudinal study

doi:10.1136/bmj.b3537

Published 24 September 2009, doi:10.1136/bmj.b3537
Cite this as: BMJ 2009;339:b3537

Research

Prostate specific antigen for early detection of prostate cancer: longitudinal study

Benny Holmström, urologist¹^,2, Mattias Johansson, postdoctoral fellow²^,3, Anders Bergh, professor of pathology⁴, Ulf-Håkan Stenman, professor of clinical chemistry⁵, Göran Hallmans, professor of nutritional research⁶, Pär Stattin, professor of urology²

¹ Department of Surgery, Gävle Hospital, S-801 87 Gävle, Sweden, ² Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, S-901 85 Umeå, Sweden, ³ International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France, ⁴ Department of Medical Biosciences, Pathology, Umeå University, ⁵ Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, POB 700, FIN-00029 HUS, Finland, ⁶ Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University

Correspondence to: M Johansson, Genetic Epidemiology Group (GEP), International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France JohanssonM{at}fellows.iarc.fr

Objective To evaluate if prostate specific antigen test attainsvalidity standards required for screening in view of recentprostate cancer screening trial results.

Design Case-control study nested in longitudinal cohort.

Setting Västerbotten Intervention Project cohort, Umeå,Sweden.

Participants 540 cases and 1034 controls matched for age anddate of blood draw.

Main outcome measure Validity of prostate specific antigen forprediction of subsequent prostate cancer diagnosis by recordlinkage to cancer registry.

Results Blood samples were drawn on average 7.1 (SD 3.7) yearsbefore diagnosis. The area under the curve for prostate specificantigen was 0.84 (95% confidence interval 0.82 to 0.86). Atprostate specific antigen cut-off values of 3, 4, and 5 ng/ml,sensitivity estimates were 59%, 44%, and 33%, and specificityestimates were 87%, 92%, and 95%. The positive likelihood ratiocommonly considered to "rule in disease" is 10; in this studythe positive likelihood ratios were 4.5, 5.5, and 6.4 for prostatespecific antigen cut-off values of 3, 4, and 5 ng/ml. The negativelikelihood ratio commonly considered to "rule out disease" is0.1; in this study the negative likelihood ratios were 0.47,0.61, and 0.70 for prostate specific antigen cut-off valuesof 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negativelikelihood ratio was 0.08.

Conclusions No single cut-off value for prostate specific antigenconcentration attained likelihood ratios formally required fora screening test. Prostate specific antigen concentrations below1.0 ng/ml virtually ruled out a prostate cancer diagnosis duringthe follow-up. Additional biomarkers for early detection ofprostate cancer are needed before population based screeningfor prostate cancer should be introduced.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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