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 uPM3™ was withdrawn from the market in June 2006, as Gen-Probe was introducing its PCA3-based test.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 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 and others.

To date, over 50 peer-reviewed publications have reported results from these studies and suggest that the high specificity of PCA3 could have an important role in prostate cancer diagnosis, such as:

  • 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, and initial 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).
  • In certain studies, the PCA3 score is higher in men whose prostate cancer show a higher Gleason score, which would indicate cancer aggressiveness.

For more information:

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

PCA3 studied in a subset of 2,400 patients from GSK’s REDUCE trial

In early March 2010, the clinical utility of PCA3 was confirmed in two large worldwide studies, conducted in a subset of about 2,400 patients from GlaxoSmithKline’s REDUCE trial of dutasteride. The studies were presented at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU) in San Francisco. The results demonstrated that PCA3 can help determine whether men suspected of having prostate cancer should undergo a repeat biopsy and can predict the risk of having an aggressive cancer.  

The first PCA3 study presented at the ASCO GU meeting originated from the placebo arm of the REDUCE trial.  This study showed that PCA3 scores were significantly correlated with a positive prostate biopsy result, and that men who had higher PCA3 scores were more likely to have prostate cancer.  Specifically, cancer was diagnosed in only 6% of men with very low PCA3 scores, but in 57% of men with very high PCA3 scores.

PCA3 scores also correlated with cancer aggressiveness (as defined by the Gleason Score): median PCA3 scores were higher in men with high-grade cancers than in those with low-grade cancers.  Finally, the PCA3 test also predicted the likelihood of a positive prostate biopsy performed two years after the test. 

The second PCA3 study originated from the patients treated with dutasteride in the REDUCE trial.  This study demonstrated that PCA3 can also be used to predict prostate biopsy outcomes in men taking dutasteride.  It confirmed earlier research that showed PCA3 outperforms serum PSA testing for prostate cancer detection, and improves diagnostic accuracy when combined with serum PSA testing and other clinical information.

PCA3 useful before the initial prostate biopsy

In April 2010, the results of a new European study of 516 men were presented at the annual meeting of the European Association of Urology. The study demonstrated that PCA3 could improve the prediction of the outcome of initial prostate biopsies while being indicative of cancer aggressiveness. In the study, patients with a PCA3 score over 35 were almost 3 times more likely to have a positive initial prostate biopsy than patients with a score under 35. The principal investigator, Pr. Alexandre de la Taille from the urology service of Henri Mondor hospital, Creteil, France, explained: “When the results of this study are combined with the results of another study we did on patients with a first negative biopsy, the PCA3 test proved to have a high predictive value as prostate cancer could be detected, at the initial or subsequent biopsy, in about 75% of men with a PCA3 score over 35. Moreover, our new study showed that with a cut-off of 20, 40% of patients could have avoided undergoing a prostate biopsy, while only 5% of the high grade cancers (all grade 7) would have been missed on the initial diagnosis.”

For more studies and scientific publications on PCA3, click here.