Prostate specific antigen for early detection of prostate cancer: longitudinal study - PubMed (original) (raw)

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

Benny Holmström et al. BMJ. 2009.

Abstract

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.

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Conflict of interest statement

Conflicts of interest: None declared.

Figures

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Fig 1 Distribution of plasma prostate specific antigen (PSA) concentrations in cases and controls. Curves indicate frequency functions of calculated normal distribution of logarithm of PSA concentrations according to mean and standard deviation in cases and controls. Histogram shows observed distribution of logarithm of PSA concentrations in cases and controls

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Fig 2 Fagan’s nomogram for calculation of post-test probabilities. Blue (solid) arrows indicate post-test probability of diagnosis during follow-up for men with prostate specific antigen (PSA) concentrations above given cut-offs. Red (broken) arrows indicate post-test probability of diagnosis during follow-up for men with PSA concentrations below given cut-offs

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