Randomized controlled screening trials for prostate cancer using prostate-specific antigen: a tale of contrasts

Rove, Kyle O.; Crawford, E. David

doi:10.1007/s00345-011-0799-4

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…For over 2 decades, the prostate specific antigen test (PSA) has been used to screen for prostate cancer (PCA) with controversial outcomes [ 1 - 3 ]. Studies have shown that there is no PSA cutoff that would simultaneously optimize the sensitivity and specificity [ 4 - 8 ].…”

Section: Introductionmentioning

confidence: 99%

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients

Brikun¹,

Nusskern²,

Gillen

et al. 2014

Biomark Res

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BackgroundMen with a negative first prostate biopsy will undergo one or more additional biopsies if they remain at high suspicion of prostate cancer. To date, there are no diagnostic tests capable of identifying patients at risk for a positive diagnosis with the predictive power needed to eliminate unnecessary repeat biopsies. Efforts to develop clinical tests using the epigenetic signature of cores recovered from first biopsies have been limited to a few markers and lack the sensitivity and specificity needed for widespread clinical adoption.MethodsWe developed methylation-specific quantitative polymerase chain reaction assays for a panel of 24 markers that are preferentially methylated in prostate cancer. We modified the bisulfite conversion conditions to allow the integration of the methylation information from multiple markers. We determined the methylation status of the 24 markers in 213 prostate biopsy cores from 104 patients, 37 prostate cancer patients and 67 controls. We performed logistic regression on combinations of markers as well as the entire panel of 24 markers to identify the best candidates for a diagnostic test.ResultsThe marker panel differentiated between cancer cores and benign cores from non-cancer patients with 100% sensitivity and 97% specificity. Furthermore, the panel detected significant methylation in benign cores from prostate cancer patients that was not present in controls. Using methylation of 5 out of 24 to define a cancer case, the analysis of a single benign biopsy core identified 62% of prostate cancer patients undergoing repeat biopsies. ROC curve analysis showed that markers commonly methylated in benign cores from cancer patients are the best candidates for a diagnostic test. The results suggest that 5 to 10 markers will be needed to achieve optimal predictive power.ConclusionsThis study shows that epigenetic field effects differ significantly between cancer patients and controls. Their detection in benign biopsy cores can form the basis of diagnostic tests to identify patients in need of repeat biopsies, reducing the cost of continued PCA screening by up to 40%. They could also be used to identify prostate cancer patients with low grade disease who are likely candidates for active surveillance or focal therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-014-0025-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients

Brikun¹,

Nusskern²,

Gillen

et al. 2014

Biomark Res

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“…The results of two recent trials have provided conflicting results with regard to the ability of prostate cancer screening to reduce prostate cancer-specific mortality 1. The Prostate Cancer Intervention versus Observation Trial (PIVOT) goes one step further by attempting to assess the efficacy of radical prostatectomy compared with observation, on overall and prostate cancer specific, survival in patients with localised prostate cancer.…”

Section: Contextmentioning

confidence: 99%

Radical prostatectomy does not improve survival compared to observation for localised prostate cancer in a prospective randomised trial

Griffin

Holzbeierlein

2012

Evid Based Med

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“…9 O rastreio do cancro da próstata com o teste PSA contribui para o aumento da sua incidência no final dos anos 80. 10,11 Este tipo de cancro é possivelmente o que apresenta maior risco de sobrediagnóstico, estimado por Brawley em 50-70%. 12 Apesar do comportamento indolente desses tumores, 90% são tratados com radiação aceitação dos rastreios médicos no género feminino (95,6%) e nos que qualificam a sua saúde como "razoável ou fraca" (96,6%).…”

Section: Introductionunclassified

“…Key words: "Secondary Prevention", "Medical Screenings", "Quaternary Prevention", "Disease Mongering", "Health Literacy" ou cirurgia o que acarreta morbilidade como incontinência urinária, disfunção sexual e efeitos gastrointestinais, em cerca de 15-20% dos casos. 11,13 Num estudo realizado por Wegwarth e Gigerenz, a maioria dos participantes de rastreios oncológicos de rotina refere não ter sido informado acerca do sobrediagnóstico e subsequente tratamento desnecessário. Cerca de 69% afirma não iniciar o rastreio se o sobrediagnóstico for tão elevado como é nos casos da mamografia e teste PSA.…”

Section: Introductionunclassified

A Capacitação dos Utentes Quanto aos Rastreios Médicos

Sousa¹,

Santiago²,

Rodrigues³

2014

RevADSO

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Randomized controlled screening trials for prostate cancer using prostate-specific antigen: a tale of contrasts

Abstract: Definitive evidence for or against screening is still lacking, as interim analyses from the ERSPC and PLCO await further follow-up in the years to come.

Cited by 8 publications

References 28 publications

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients

Radical prostatectomy does not improve survival compared to observation for localised prostate cancer in a prospective randomised trial

A Capacitação dos Utentes Quanto aos Rastreios Médicos

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