The use of PCA3 in the diagnosis of prostate cancer

Abstract

Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been its lack of specificity, which results in a high negative biopsy rate. Consequently, a large population of men with chronically elevated serum PSA and one or more negative biopsies has emerged. More accurate tests are needed that can help identify which patients are at high risk of developing prostate cancer, and for whom repeat prostate biopsies are mandatory. To improve the specificity of prostate cancer diagnosis, prostate-cancer-specific markers, such as prostate cancer gene 3 (PCA3), are needed. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. Quantification of PCA3 mRNA levels in urine was found to help predict the outcome of prostate biopsies. The intensive and time-consuming reverse-transcriptase polymerase chain reaction PCA3 urine test has been translated successfully into the fast and easy transcription-mediated amplification (TMA)-based PCA3 test. This test is the first RNA-based molecular diagnostic assay in body fluids for prostate cancer that is available to urologists. This Review describes the translation of the molecular marker PCA3 from the research laboratory to clinical practice.

Key Points

  • Unlike serum PSA, PCA3 is specific for prostate cancer and is not affected by prostate volume or other non-cancerous prostate conditions

  • The PCA3 score correlates with the result of a subsequent biopsy; in men with a high PCA3 score, the likelihood of a positive prostate biopsy is increased

  • Preliminary data demonstrate a correlation between PCA3 score and prostate cancer prognostic markers; therefore, PCA3 might identify men who have clinically insignificant prostate cancer and are candidates for active surveillance

  • The PCA3 test is the first fully translated molecular assay in body fluids that is a valuable tool in predicting biopsy outcome

  • Combining PCA3 as a continuous variable with other clinical or pathological factors or biomarkers (for example, TMPRSS2ERG gene fusions) will provide more-accurate prostate cancer diagnosis and prognosis

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Figure 1: Structure of the PCA3 transcription unit.
Figure 2: Sensitivity and specificity of PCA3 testing for detecting prostate cancer.
Figure 3: The correlation of PCA3 score (determined with the TMA-based PCA3 test) with the percentage of men with positive prostate biopsies.
Figure 4: PCA3 score and clinical relevance of prostate cancers.

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Acknowledgements

The authors would like to thank Dr. Gerald W. Verhaegh (Experimental Urology, Radboud University Nijmegen Medical Centre) and Frank P. Smit (NovioGendix, Nijmegen) for their assistance in critically reading this manuscript.

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Correspondence to Jack A. Schalken.

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J. A. Schalken has been a speaker for Gen-Probe Inc.

NovioGendix is specialized in molecular diagnostics and offers services (e.g. the PCA3 test) to urologists and clinicians throughout Europe. Daphne Hessels is an employee of NovioGendix.

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Hessels, D., Schalken, J. The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol 6, 255–261 (2009). https://doi.org/10.1038/nrurol.2009.40

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