PCA3 Test – For Healthcare Practitioners

First generation of a PCA3-based test

In 2002, DiagnoCure completed the development of a first generation PCA3 assay, uPM3™, a non-invasive test which enabled the detection of PCA3 RNA expression in prostate cells present in the urine from men in the population at risk. It used an amplification and a detection technique to evaluate the overexpression of the PCA3 RNA. In fact, DiagnoCure’s test detected the presence of two RNAs: PSA mRNA, specific to prostate tissue, and PCA3 RNA, overexpressed in prostate cancer. The PSA mRNA level allowed to confirm the presence of prostate cells in sample and thus acted as a qualitative control. uPM3™ was withdrawn from the market in June 2006, as Gen-Probe was introducing its PCA3-based test.

Gen-Probe’s PCA3-based test

In November 2003, DiagnoCure signed a license and collaboration agreement with Gen-Probe Inc. for the development and commercialization of a second generation of a test based on the PCA3 marker on their proprietary platform.

The Gen-Probe technical team has developed a “quantitative ratio” format of PCA3 RNA over PSA mRNA, which provided more accurate results than the qualitative format employed in the uPM3™ assay. For example, the “non-evaluable rate”, that is the percent of samples not yielding sufficient PSA mRNA for the sample to be tested, has decreased to fewer than 5% of samples.

Pre-clinical research studies have been initiated with a Research Use Only (RUO) version of the test and reported at major meetings by investigators from Gen-Probe and major cancer research centers including the Urological Sciences Research Foundation, the MD Anderson Cancer Center, the Johns Hopkins University, the University of Washington and the University of Nijmegen. In 2006, Gen-Probe also initiated clinical research studies at seven prestigious European universities.

Preliminary results from these studies (see below for highlights of two recent studies) suggest that the high specificity of PCA3 could have an important role in prostate cancer diagnosis:

  • PCA3 ScoreStudies have shown that PCA3 RNA is overexpressed, relative to benign cells, by 60 to 100-fold in more than 90% of prostate tumors.
  • Studies are reporting higher specificity for the PCA3-based test compared to the prostate specific antigen (PSA) following a first negative biopsy.
  • The PCA3 score appears correlated to the risk of a positive repeat biopsy.
  • Unlike PSA, the PCA3 score appears NOT to be correlated with diseases that increase the size of the prostate gland, such as benign prostatic hyperplasia (BPH).

For more information:

Highlights of two recent studies confirming the potential of the PCA3 marker for the diagnosis of prostate cancer

Preliminary results of European multi-center study, March 2007 [1]

A poster presented at the European Association of Urology in March 2007 indicated that the new Gen-Probe PROGENSA™ PCA3 test for prostate cancer yielded greater diagnostic accuracy than the free prostate specific antigen (free PSA) test on men with previous negative biopsy.

Based on the interim analysis presented at the EAU meeting, the researchers concluded that the PROGENSA™ PCA3 assay was better than free PSA at predicting the result of the repeat biopsy. They reported the PCA3 test had a specificity of 73% in the study, compared to only 16% for free PSA. The researchers also said that higher PCA3 scores correlated with a greater likelihood of a positive repeat biopsy. For example, men with an elevated PCA3 score had a 41% likelihood of having a positive repeat biopsy, while men with a low PCA3 score had only a 16% likelihood.

Promising data on research test for prostate cancer published in UROLOGY®, March 2007 [2]

In this 233-men study, Gen-Probe’s research PCA3 predicted the results of repeat biopsies more accurately than traditional prostate specific antigen (PSA) testing. The study included men with serum PSA levels of at least 2.5 ng/mL from three North American hospitals. All the men previously had a negative biopsy, and were scheduled for a follow-up biopsy. The median age of the men was 64, and their median serum PSA level was 6.1 ng/mL. In the study, the researchers collected urine from the men after a digital rectal examination. Approximately 97% of the samples were “informative,” meaning they contained adequate genetic material for analysis. Repeat prostate biopsies revealed prostate cancer in about 27% of these men.

The researchers found that the risk of a positive repeat biopsy correlated with the PCA3 score. For example, among the 26 men in the study who had a PCA3 score of less than 5, only 12% had a positive repeat biopsy. In contrast, among the 18 men with a PCA3 score greater than 100, 50% had a positive repeat biopsy. For all the men in the study, the PCA3 research assay yielded an odds ratio of 3.6, meaning that men with an elevated PCA3 score were 3.6 times more likely to have a positive repeat biopsy than men with a normal PCA3 score.

In addition, the researchers used a statistical method called receiver operating characteristic (ROC) curve analysis to assess the ability of the PCA3 research assay to predict the result of the follow-up prostate biopsy. For the PCA3 score, the area under the ROC curve was 0.68. In comparison, the serum PSA assay yielded an area under the curve of 0.52, “indicating little better than a ‘coin toss’ probability of predicting the presence of prostate cancer,” according to the authors. In the study, the PCA3 assay had a sensitivity of 58%, and a specificity of 72%.

 

[1] Alexander Haese et al., The value of the PCA3 Assay in guiding decision which men with a negative prostate biopsy need immediate repeat biopsy: preliminary European data, EAU, March 2007

[2] Leonard S. Marks et al., PCA3 Molecular Urine Assay for prostate cancer in men undergoing repeat biopsy, UROLOGY, 69: 532-535, March 2007