PCA3: A Molecular Urine Assay for Predicting Prostate Biopsy Outcome

Deras, Ina L.; Aubin, Sheila M. J.; Blase, Amy; Day, John; Koo, Seongjoon; Partin, Alan W.; Ellis, William; Marks, Leonard S.; Fradet, Yves; Rittenhouse, Harry G.; Groskopf, Jack

doi:10.1016/j.juro.2007.11.038

Cited by 391 publications

(284 citation statements)

References 18 publications

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“…40 Despite good performance, the uPM3 was withdrawn from the market after introduction of the APTIMA assay (Gen-Probe, San Diego, CA, USA; PROGENSA for European countries) which provides several advantages: (1) The ability to use whole urine and detection of lower concentrations of RNA in clinical samples (as opposed to urine sediments used in methods discussed above); (2) The target capture technology using magnetic particles is more quantitative and user friendly than the RNA extraction methods required for RT-PCR; (3) The APTIMA PCA3 assay can be completed in o6 h, and because of its robustness and reproducibility it can be implemented in the clinical laboratory. 41 Several large studies have confirmed the good performance of this assay, [42][43][44][45][46] and the clinical results have recently been reviewed. 47 The addition of PCA3 to the urologist's diagnostic tools will not result in a state of certainty but the diagnostic sensitivity, specificity and predictive value are incrementally improved by its inclusion.…”

Section: Prostate Cancer Antigenmentioning

confidence: 87%

Urine markers in monitoring for prostate cancer

Jamaspishvili

Král

Khomeriki

et al. 2009

Prostate Cancer Prostatic Dis

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The major advantages of urine-based assays are their noninvasive character and ability to monitor prostate cancer with heterogeneous foci. Almost all urine-detectable prostate-specific markers have been recently reviewed. For this reason, we focus here on only a few promising markers which have been independently evaluated (in particular PCA3, fusion genes, TERT, AMACR, GSTP1, MMP9 and VEGF) and very recent ones (ANXA3 and sarcosine). The emphasis is also on multiplex biomarker analysis and on microarray-based analysis of fusion genes. A combination of multiple urine biomarkers may be valuable in the case of men with persistently elevated serum prostatespecific antigen and a history of negative biopsies. The emerging urine tests should help in both early diagnosis of prostate cancer and identifying aggressive tumors for radical treatment.

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Section: Prostate Cancer Antigenmentioning

confidence: 87%

Urine markers in monitoring for prostate cancer

Jamaspishvili

Král

Khomeriki

et al. 2009

Prostate Cancer Prostatic Dis

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“…However, 12 additional studies included matched results of PCA3 and the comparators but enrolled men with both initial and repeat biopsies or they did not report biopsy history. 10,11,[35][36][37][38][39][40][41][42][43][44] Most often, the results from these studies were not stratified by biopsy history.…”

Section: Clinical Validitymentioning

confidence: 99%

“…Fifteen studies [9][10][11]30,32,[34][35][36][37][38][39][40][41][42][43]46 reported AUC estimates for tPSA and PCA3 in the same population. Overall, 13 [9][10][11]30,32,34,35,37,38,[40][41][42]46 of the15 studies found that the AUC of PCA3 was higher than that of tPSA.…”

Section: Clinical Utilitymentioning

confidence: 99%

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Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

Calonge

Klein

Berg

et al. 2014

Genetics in Medicine

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Summary of recommendations:The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found insufficient evidence to recommend prostate cancer antigen 3 (PCA3) testing to inform decisions for when to rebiopsy previously biopsy-negative patients for prostate cancer or to inform decisions to conduct initial biopsies for prostate cancer in at-risk men (e.g., previous elevated prostate-specific antigen test or suspicious digital rectal examination).The EGAPP Working Group found insufficient evidence to recommend PCA3 testing in men with cancer-positive biopsies to determine if the disease is indolent or aggressive in order to develop an optimal treatment plan.Based on the available evidence, the overall certainty of clinical validity to predict the diagnosis of prostate cancer using PCA3 is deemed "low. " The EGAPP Working Group discourages clinical use for diagnosis unless further evidence supports improved clinical validity.Based on the available evidence, the overall certainty of net health benefit is deemed "low. " The EGAPP Working Group discourages clinical use unless further evidence supports improved clinical outcomes.Rationale: It has been suggested that PCA3 testing in the general male population might lead to earlier diagnosis and management changes (e.g., earlier detection and earlier initiation or higher rates of medical interventions) that improve outcomes. EGAPP Working Group found no direct evidence to support this possibility, so we sought indirect evidence aimed at documenting the extent to which PCA3 testing alters prostate cancer diagnosis or management, alone and in combination with traditional clinical management factors, and the extent to which this testing improves health outcomes.Analytic validity: Assay-related evidence was deemed adequate for the PROGENSA PCA3 assay approved by the US Food and Drug Administration, available from Gen-Probe. Very few studies were available that investigated preanalytical effects, analytical performance, and diagnostic accuracy of other quantitative assays for PCA3.Clinical validity: Evidence on clinical validity was rated inadequate to derive any conclusions about performance of PCA3 testing to inform decisions for when to rebiopsy previously biopsy-negative patients for prostate cancer, or to inform decisions to conduct initial biopsies for prostate cancer in at-risk men (e.g., previous elevated prostate-specific antigen test or suspicious digital rectal examination). Furthermore, there was little evidence to derive any conclusions about performance of PCA3 testing in men with cancer-positive biopsies to determine if the disease is indolent or aggressive in order to develop an optimal treatment plan. Clinical utility:No studies were available to provide direct evidence on the balance of benefits and harms related to PCA3 testing for diagnosis and management in the general male population. Evidence for other populations (e.g., high risk) was not evaluated in the review.

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“…6 Elevations in PCA3 gene transcripts in post-digital rectal examination (DRE) urine have been shown to be associated with prostate cancer in patients undergoing initial and repeat prostate biopsy. 7 In men undergoing repeat biopsy, studies have suggested that PCA3 may be superior to both PSA 8 and free PSA 9 in predicting the presence of prostate cancer. Furthermore, inclusion of PCA3 improved predictive accuracy of a multivariable model that evaluated probability of having prostate cancer in men with elevated PSA, with or without prior biopsy in a recent study by Chun et al 10 Based on these findings, PCA3 was included in a multivariable nomogram designed to predict the presence of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Utility of PCA3 in patients undergoing repeat biopsy for prostate cancer

Reese

Cooperberg

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND: Men with persistently elevated and/or rising PSA levels after negative prostate biopsy often undergo multiple repeat biopsies. Prostate cancer antigen 3 (PCA3) has emerged as a predictor of prostate cancer. METHODS:We sought to define the utility of PCA3 in combination with other clinical data in predicting the risk of prostate cancer on repeat biopsy. We retrospectively obtained PCA3, PSA, PSA density (PSAD), digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings from 103 patients at a single institution who had at least one prior negative prostate biopsy. The sensitivity and specificity of PCA3 in detecting prostate cancer was determined. Receiver operating characteristics curves were produced for each variable individually and in multivariable analysis, controlling for PCA3, PSAD, TRUS, PSA and DRE. A nomogram was created, internally validated and compared to another recently published nomogram. RESULTS:Of the 103 patients, 37 (31%) had prostate cancer on repeat biopsy. The sensitivity and specificity of PCA3 (using a cut point of 25) was 0.67 and 0.64, respectively. In multivariable analyses, PCA3 was independently associated with prostate cancer (odds ratio: 1.02, 95% confidence interval: 1.01-1.04), with area under the curve (AUC) of 0.64. A multivariable model containing PCA3, PSAD, PSA, DRE and TRUS findings showed the most diagnostic accuracy (AUC: 0.82). CONCLUSIONS:In the setting of prior negative biopsies, PCA3 was independently associated with prostate cancer in a multivariable model. In combination with other clinical data, PCA3 is a valuable tool in assessing the risk of prostate cancer on repeat biopsy.

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PCA3: A Molecular Urine Assay for Predicting Prostate Biopsy Outcome

Cited by 391 publications

References 18 publications

Urine markers in monitoring for prostate cancer

Urine markers in monitoring for prostate cancer

Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

Utility of PCA3 in patients undergoing repeat biopsy for prostate cancer

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