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Prostate specific antigen for early detection of prostate cancer: longitudinal study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC), Lyon, France.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2009 (English)In: BMJ (Clinical research ed.), ISSN 1468-5833, Vol. 339, b3537- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 339, b3537- p.
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
URN: urn:nbn:se:umu:diva-26272DOI: 10.1136/bmj.b3537ISI: 000270231800002PubMedID: 19778969OAI: oai:DiVA.org:umu-26272DiVA: diva2:241332
Available from: 2009-10-02 Created: 2009-10-02 Last updated: 2016-03-07Bibliographically approved
In thesis
1. Early diagnosis and treatment of prostate cancer: observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project
Open this publication in new window or tab >>Early diagnosis and treatment of prostate cancer: observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Tidig diagnostik och behandling av prostatacancer  : observationsstudier i Nationella Prostatacancerregistret och Västerbottens interventionsprojekt
Abstract [en]

Prostate-specific antigen (PSA) testing has caused a steep increase in the incidence of prostate cancer, especially the incidence of localised low risk disease. In order to decrease the overdiagnosis accompanied by PSA testing, analysis of inherited genetic variants have been suggested as potential tools for clinical assessment of disease risk. With the aim of minimizing overtreatment and postpone side-effects of curative treatment for low risk prostate cancer, active surveillance, a treatment strategy with initial surveillance and deferred radical prostatectomy at the time of progression has evolved. 

The aim of this thesis was to study the validity of PSA (paper I) and inherited genetic variants (paper II) for early diagnosis of prostate cancer, to assess the extent of PSA testing in Sweden (paper III), and to study the safety of deferred radical prostatectomy in localised low to intermediate risk prostate cancer (paper IV).

The study designs were i) case-control studies nested within the Västerbotten intervention project (paper I and II), ii) observational study in the Cancer Register of Sweden (paper III), and iii) observational study in the NPCR Follow-up study (paper IV).

PSA had a high validity in predicting a prostate cancer diagnosis with an area under the receiver operating characteristics (ROC) curve of 0.86 (95% CI, 0.84 to 0.88). A combined test, including PSA, the ratio of free to total PSA, and 33 single nucleotide polymorphisms (SNPs) in a genetic risk score, increased the area under curve to 0.87 (95% CI, 0.85 to 0.89). The estimated uptake of PSA testing among men aged 55 to 69 years increased from zero to 56% between 1997 and 2007 and there were large variations in the uptake of PSA testing between counties in Sweden. After a median follow-up time of eight years there was no significant difference in presence of any one or more adverse pathology features or prostate cancer specific mortality after primary compared to deferred radical prostatectomy in localised low to intermediate risk prostate cancer.

Results from these studies indicate that PSA and the hitherto identified SNPs are not suitable biomarkers in single-test prostate cancer screening. It is possible to estimate the uptake of PSA testing on a population level. Initial surveillance and deferred radical prostatectomy represent a feasible treatment strategy in localised low to intermediate risk prostate cancer.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. 58 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1397
Keyword
Prostate cancer, prostate-specific antigen, single nucleotide polymorphism
National Category
Urology and Nephrology
Research subject
Urology
Identifiers
urn:nbn:se:umu:diva-42843 (URN)978-91-7459-134-7 (ISBN)
Public defence
2011-05-13, Sal E04, Byggnad 6E, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
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Available from: 2011-04-21 Created: 2011-04-14 Last updated: 2011-04-21Bibliographically approved

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