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Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study

BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c4521 (Published 14 September 2010) Cite this as: BMJ 2010;341:c4521
  1. Andrew J Vickers, associate attending research methodologist1,
  2. Angel M Cronin, research biostatistician1,
  3. Thomas Björk, senior consultant2,
  4. Jonas Manjer, associate professor2,
  5. Peter M Nilsson, professor2,
  6. Anders Dahlin, data manager2,
  7. Anders Bjartell, professor2,
  8. Peter T Scardino, department chair3,
  9. David Ulmert, research fellow/resident45,
  10. Hans Lilja, attending research clinical chemist/professor (adjunct)67
  1. 1Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
  2. 2Department of Clinical Sciences (Urological Cancers, Medicine, Surgery), Lund University, University Hospital in Malmo, 205 02, Malmo, Sweden
  3. 3Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York
  4. 4Department of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York
  5. 5Departments of Clinical Sciences and Laboratory Medicine, Lund University, Skane University Hospital, 205 02 Malmo
  6. 6Department of Clinical Laboratories, Surgery and Medicine, Memorial Sloan Kettering Cancer Center, New York
  7. 7Department of Laboratory Medicine, Lund University, Skane University Hospital, 205 02 Malmo
  1. Correspondence to: H Lilja, Department of Clinical Laboratories, Surgery and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA liljah{at}mskcc.org
  • Accepted 28 June 2010

Abstract

Objective To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk.

Design Case-control study with 1:3 matching nested within a highly representative population based cohort study.

Setting General population of Sweden taking part in the Malmo Preventive Project. Cancer registry at the National Board of Health and Welfare.

Participants 1167 men aged 60 who provided blood samples in 1981 and were followed up to age 85.

Main outcome measures Metastasis or death from prostate cancer.

Results The rate of screening during the course of the study was low. There were 43 cases of metastasis and 35 deaths from prostate cancer. Concentration of prostate specific antigen at age 60 was associated with prostate cancer metastasis (area under the curve 0.86, 95% confidence interval 0.79 to 0.92; P<0.001) and death from prostate cancer (0.90, 0.84 to 0.96; P<0.001). The greater the number for the area under the curve (values from 0 to 1) the better the test. Although only a minority of the men with concentrations in the top quarter (>2 ng/ml) develop fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with concentrations at the median or lower (≤1 ng/ml) were unlikely to have clinically relevant prostate cancer (0.5% risk of metastasis by age 85 and 0.2% risk of death from prostate cancer).

Conclusions The concentration of prostate specific antigen at age 60 predicts lifetime risk of metastasis and death from prostate cancer. Though men aged 60 with concentrations below the median (≤1 ng/ml) might harbour prostate cancer, it is unlikely to become life threatening. Such men could be exempted from further screening, which should instead focus on men with higher concentrations.

Footnotes

  • We thank Gun-Britt Eriksson and Mona Hassan Al-Battat for expert assistance with immunoassays, and Janet Novak, at Helix Editing, for her assistance with editing of the manuscript.

  • Contributors: HL and AJV designed the study. HL and PTS obtained funding. PMN, JM, and AD maintained and supervised the Malmo cohort database and bio-repository. HL and DU supervised biomarker measurements. DU, TB, AB, and AD gathered data on patients. AJV and AMC analysed data. HL, AMC, PTS, and AJV helped to interpret the results. AJV and HL wrote the paper. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis, and all authors approved the final manuscript. HL is guarantor.

  • Funding: This work was supported by the National Cancer Institute (grant numbers R21-CA127768-01A1, P50-CA92629); the Swedish Cancer Society (3455); the Swedish Research Council (Medicine) (20095); the Sidney Kimmel Center for Prostate and Urologic Cancers; David H Koch through the Prostate Cancer Foundation; and Fundación Federico SA. The manuscript editing was paid for by internal funds at Memorial Sloan-Kettering Cancer Center. The study sponsors had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that HL holds patents for free PSA and hK2 assays.

  • Ethical approval: The study was approved by the ethics committee at Lund University. Consent was not obtained from study participants, but the presented data are anonymised and risk of identification is minimal.

  • Data sharing: A full dataset along with the statistical code used for analysis are available from the authors on request, and from the Swedish national data archive (http://www.ssd.gu.se/en). These data can be used only for replication of the analyses published in this paper or for private study. Express written permission must be sought from the authors for any other data use.

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