Clinical use of urine PCA3 mRNA testing; Increased sensitivity and specificity of urine prostate cancer assays can aid earlier detection and risk assessment

Shappell SB, Marks LS. Urology Times September 2009

• This paper, published at the web-based journal Urology Times, discusses the PCA3 (Prostate CAncer gene 3) Assay and its use in clinical practice
• The main advantage of the PCA3 Assay is its high specificity for diagnosing prostate cancer, which is lacking for prostate specific antigen (PSA)
• In men with a prior negative biopsy and an elevated PSA level, the PCA3 Assay has a sensitivity of 60-70% and a specificity of 70-80%
• PCA3 is expressed only in the prostate. Unlike PSA, increased expression of PCA3 is essentially specific to prostate cancer cells, which may explain the high specificity of the PCA3 Assay for the detection of prostate cancer
• In contrast to serum PSA, PCA3 is not increased in benign prostate tissues affected by inflammation (prostatitis) and in other benign conditions of the prostate such as benign prostatic hyperplasia (BPH)
• The PCA3 Score may be correlated with the aggressiveness of prostate cancer (i.e. tumour volume, Gleason score). This might be related to the presence of intraductal carcinoma of the prostate (spread of invasive carcinoma within pre-existing ducts) which may also be associated with more aggressive cancer. This should be further evaluated
• The PCA3 Assay specimen collection procedure described in this article is for the ASR (analyte specific reagent) Assay currently available in the U.S.  The CE-marked PROGENSA PCA3 Assay has improved sample stability and does not require frozen storage.  Samples are stable up to 5 days at room temperature for shipment to a testing facility
• The PCA3 Assay is very robust with an informative rate of over 98%, and the inter-laboratory concordance evaluated by testing identical urine samples is high
  In clinical practice, the PCA3 Assay can be used to guide repeat biopsy decisions. In addition, the PCA3 Assay may be used for guiding initial biopsy decisions and to predict clinically insignificant cancer to identify men who could be candidates for active surveillance
• The PCA3 Score cut-off of 35 has the best diagnostic accuracy (i.e. combination of sensitivity and specificity) for predicting repeat biopsy outcome. However, the PCA3 Score is a continuous variable with a higher score indicating an increased likelihood of a positive biopsy. Ideally the PCA3 Score should be used with other clinical information for guiding biopsy decisions in clinical practice

Reviewed by

Prof. J. Schalken

Editorial comment

This is a nice review underlining the clinical utility of the PCA3 test, focussing on where it can complement serum PSA testing in its weaknesses. The review shows that in all studies the specificity of PCA3 is confirmed, as is the sensitivity. The authors conclude that the PCA3 score will in the future likely be incorporated as a continuous parameter. In fact, the implementation in a nomogram has also been reported in 2009 (http://deb.uthscsa.edu/URORiskCalc/Pages/calcsPCA3.jsp )

More information

http://urologytimes.modernmedicine.com/urologytimes/Modern+Medicine+Now/Clinical-use-of-urine-PCA3-mRNA-testing/ArticleStandard/Article/detail/624481