Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial

Määttänen, Liisa; Hakama, Matti; Tammela, Teuvo L.J.; Ruutu, Mirja; Ala‐Opas, Martti; Juusela, Harri; Martikainen, Petri; Stenman, Ulf‐Hǎkan; Auvinen, Anssi

doi:10.1038/sj.bjc.6603522

Cited by 18 publications

(4 citation statements)

References 37 publications

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“…The specificity of the PSA test has been reported very consistently as 90% or slightly higher (4)(5)(6). Much wider variability in sensitivity has been reported, ranging from 20% to 95% (7)(8)(9).…”

Section: Introductionmentioning

confidence: 93%

Test Sensitivity in the European Prostate Cancer Screening Trial: Results from Finland, Sweden, and the Netherlands

Auvinen

Raitanen²,

Moss³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Test sensitivity pertains to the ability of a test to identify subjects with the target disorder. In cancer screening, test sensitivity can be estimated using interval cancer incidence as an indicator of falsenegative result. A randomized trial provides the optimal approach for estimating test sensitivity, as the control arm provides the expected rates. We estimated the sensitivity of the prostate-specific antigen test using incidence method, i.e., based on incidence of interval cancer among subjects with negative screening results, compared with that in the control arm. Data from three centers in the European randomized screening trial were used to estimate interval cancer incidence (I I ) among 39,389 men with negative screening tests. This was compared with incidence among the 79,525 men in the control arm of the trial (I c ) to estimate test sensitivity (S = 1 À I I / I C ). Confidence intervals were calculated using simulations, assuming that the number of cases follows a Poisson distribution. The estimated test sensitivity following the first screen was 0.87 (0.83-0.92) in Finland, 0.87 (0.62-1.00) in Sweden, and 0.93 (95% confidence interval, 0.90-0.96) in the Netherlands. There was some indication of a higher test sensitivity for aggressive cancers (0.85-0.98 for non -organconfined cases or Gleason 8-10) and for the second screening round (approximately 0.85-0.95). Test sensitivity varied to some extent between the three centers in the European trial, probably reflecting variation in screening protocols, but was acceptable in the first screening round, and may be better for aggressive cancers and in the second screening round.

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Section: Introductionmentioning

confidence: 93%

Test Sensitivity in the European Prostate Cancer Screening Trial: Results from Finland, Sweden, and the Netherlands

Auvinen

Raitanen²,

Moss³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…9 Studies of this design can provide accurate data on the positive predictive value of prostate specific antigen for diagnosis of prostate cancer, as men with high prostate specific antigen concentrations have biopsy for verification of the diagnosis. These studies can also provide relatively accurate estimates of specificity given that prostate cancer is relatively rare among men with low prostate specific antigen concentrations 1011 12 However, in cross sectional studies, cancer status is not verified in men with prostate specific antigen concentrations below the threshold for biopsy, so such studies cannot provide accurate estimates of sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…These studies can also provide relatively accurate estimates of specificity given that prostate cancer is relatively rare among men with low prostate specific antigen concentrations. 10 11 12 However, in cross sectional studies, cancer status is not verified in men with prostate specific antigen concentrations below the threshold for biopsy, so such studies cannot provide accurate estimates of sensitivity. Estimates of sensitivity are necessary for calculation of likelihood ratios, 13 which describe the likelihood that a given test result would be expected in a person with a disease compared with the likelihood that the same result would be expected in a person without the disease.…”

Section: Introductionmentioning

confidence: 99%

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

Holmström

Johansson

Bergh

et al. 2009

BMJ

106

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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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“…The proportion of FP results is likely to increase with age, as prostatic diseases, such as chronic prostatitis and BPH, become more common (Koskimäki et al, 1998;Rhodes et al, 1999;Wright et al, 2002). The proportion of FP results has been estimated to be 7 -8% (Lafata et al, 2004;Määttänen et al, 2007) per screen (with 1 year of follow-up after the test). In repeated screening, the cumulative proportion of FP results was recently estimated at 10.4% with four PSA tests and over 3 years of follow-up (Croswell et al, 2009).…”

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confidence: 99%

False-positive screening results in the Finnish prostate cancer screening trial

et al. 2010

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BACKGROUND: There is evidence that prostate cancer (PC) screening with prostate-specific antigen (PSA) serum test decreases PC mortality, but screening has adverse effects, such as a high false-positive (FP) rate. We investigated the proportion of FPs in a population-based randomised screening trial in Finland. METHODS: Finland is the largest centre in the European Randomized Study of Screening for Prostate Cancer. We have completed three screening rounds with a 4-year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level of 4.0 ng ml À1 ; in addition, men with PSA 3.0 -3.9 and a positive auxiliary test were referred. An FP result was defined as a positive screening result without cancer in biopsy within 1 year from the screening test. RESULTS: The proportion of FP screening results varied from 3.3 to 12.1% per round. Of the screened men, 12.5% had at least one FP during three rounds. The risk of next-round PC following an FP result was 12.3 -19.7 vs 1.4 -3.7% following a screen-negative result (depending on the screening round), risk ratio 3.6 -9.9. More than half of the men with one FP result had another one at a subsequent screen. Men with an FP result were 1.5 to 2.0 times more likely to not participate in subsequent rounds compared with men with a normal screening result (21.6 -29.6 vs 14.0 -16.7%). CONCLUSION: An FP result is a common adverse effect of PC screening and affects at least every eighth man screened repeatedly, even when using a relatively high cutoff level. False-positive men constitute a special group that receives unnecessary interventions but may harbour missed cancers. New strategies are needed for risk stratification in PC screening to minimise the proportion of FP men.

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Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial

Cited by 18 publications

References 37 publications

Test Sensitivity in the European Prostate Cancer Screening Trial: Results from Finland, Sweden, and the Netherlands

Test Sensitivity in the European Prostate Cancer Screening Trial: Results from Finland, Sweden, and the Netherlands

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

False-positive screening results in the Finnish prostate cancer screening trial

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