Prostate specific antigen for early detection of prostate cancer: longitudinal studyBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3537 (Published 24 September 2009) Cite this as: BMJ 2009;339:b3537
- Benny Holmström, urologist12,
- Mattias Johansson, postdoctoral fellow23,
- Anders Bergh, professor of pathology4,
- Ulf-Håkan Stenman, professor of clinical chemistry5,
- Göran Hallmans, professor of nutritional research6,
- Pär Stattin, professor of urology2
- 1Department of Surgery, Gävle Hospital, S-801 87 Gävle, Sweden
- 2Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, S-901 85 Umeå, Sweden
- 3International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
- 4Department of Medical Biosciences, Pathology, Umeå University
- 5Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, POB 700, FIN-00029 HUS, Finland
- 6Department 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
- Accepted 5 June 2009
Objective To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate 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 and date of blood draw.
Main outcome measure Validity of prostate specific antigen for prediction of subsequent prostate cancer diagnosis by record linkage to cancer registry.
Results Blood samples were drawn on average 7.1 (SD 3.7) years before diagnosis. The area under the curve for prostate specific antigen was 0.84 (95% confidence interval 0.82 to 0.86). At prostate specific antigen cut-off values of 3, 4, and 5 ng/ml, sensitivity estimates were 59%, 44%, and 33%, and specificity estimates were 87%, 92%, and 95%. The positive likelihood ratio commonly considered to “rule in disease” is 10; in this study the positive likelihood ratios were 4.5, 5.5, and 6.4 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. The negative likelihood ratio commonly considered to “rule out disease” is 0.1; in this study the negative likelihood ratios were 0.47, 0.61, and 0.70 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negative likelihood ratio was 0.08.
Conclusions No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a screening test. Prostate specific antigen concentrations below 1.0 ng/ml virtually ruled out a prostate cancer diagnosis during the follow-up. Additional biomarkers for early detection of prostate cancer are needed before population based screening for prostate cancer should be introduced.
We thank all participants in the Northern Sweden Health and Disease Cohort project, and we thank Åsa Ågren, Charlotte Ingri, and Björn Tavelin for their assistance in project coordination and data management.
Contributors: PS, MJ, and GH contributed to study conception and design. PS, BH, MJ, U-HS, and AB contributed to analysis and interpretation of the data. U-HS did the biochemical analysis. AB was responsible for revision of core biopsies. BH, MJ, and PS contributed to drafting of the article. All authors critically revised the article for important intellectual content and gave final approval. GH provided the study participants. MJ provided statistical expertise. PS obtained funding. BH, MJ, and PS are the guarantors.
Funding: This study was supported by grants from the Swedish Cancer Foundation and the Lion’s Cancer Research Foundation at Umeå University. The funding source had no role in the study design; collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The researchers were all independent from the funding source.
Conflicts of interest: None declared.
Ethical approval: The research ethical committee at Umeå University Hospital approved of the study.
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