Moleculaire diagnostiek van prostaatkanker met PCA3 (Molecular diagnostics of prostate cancer using PCA3)

J. Schalken, Kanker 2008;32(3):32-4 (article in Dutch)

• This review (article in Dutch) discusses the role of Prostate CAncer gene 3 (PCA3) in the diagnosis and prognosis of prostate cancer (PCa).
• There is a need for biomarkers that can aid in the diagnosis of clinically significant PCa.
  PCA3 mRNA was found to be minimally expressed in normal or benign prostate tissue, but highly over-expresssed (60-100 fold) in more than 90% of PCa specimens¹.
• PCA3 is the most PCa-specific gene described to date.
• The PCA3 Assay, that measures PCA3 mRNA in urine samples, has been shown to be a sensitive test with a high specificity for detecting PCa².
• In 2007, the CE-marked PROGENSATM  PCA3 Assay became available in Europe as a simple urine test to aid in the diagnosis of PCa. The urine sample is taken after a digital rectal examination (DRE) according to a standardized procedure and the PCA3 Assay is performed with ‘state of the art’ technology for molecular diagnostics.
• Two prospective multi-centre studies in the US and Europe have shown the value of the PCA3 Score in predicting the presence of PCa in the repeat biopsy in men with 1-2 previous negative biopsies^3,4. 
• Recent studies also support the use of the PCA3 Assay to aid in the decision on whether or not to perform a first biopsy^5,6.
• In addition, it has been demonstrated that the PCA3 Score may discriminate indolent from clinically significant PCa⁷.
• The PCA3 Assay is clinically available and may contribute in the diagnosis and treatment of PCa (see table). The role of PCA3 as a prognostic factor is promising but needs to be further evaluated.

Table

1) Bussemakers, MJ et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999;59:5975-9
2) Hessels D, et al. DD3 (PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 2003;44:8-15
3) Marks LS, et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 2007;69:532-5
4) Haese A, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54:1081-8
5) Deras IL, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 2008;179:1587-92
6) Sokoll LJ, et al. A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance, and diagnostic accuracy. Clinica Chimica Acta 2008;289:1-6
7) Nakanishi H, et al. PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 2008;179:1804-10

Reviewed by

Prof. H. van Poppel, Prof. J. Schalken

Editorial comment

The role for the use of PCA3 in clinical practice becomes more and more precise. Its role in counseling patients that are candidates for a repeat biopsy (men with previous negative biopsies) gets well established. In the presence of a high PCA3 Score the patient has a significantly higher chance of having prostate cancer, having a higher stage and higher grade, that is probably best to be detected early. With a favourable PCA3 Score the chance of having significant cancer is low but it should be noted that even very low PCA3 scores cannot exclude the presence of cancer.

The role of the use of the PCA3 Assay in patients that never underwent a biopsy is under study. Similarly, studies are planned on cysto-prostatectomy specimens of bladder cancer patients to elucidate the relation between clinically unsuspicious prostates that often present with insignificant or indolent cancers.