The PCA3 or prostate cancer gene 3 assay was approved some time ago for commercial use in Europe. It has not yet been approved by the U.S. Food and Drug Administration. What are the real differences between this test and the PSA test that we are all more accustomed too?
Last October Prof. Jack Schalken of the University of Nijmegen in the Netherlands (one of the developers of the PCA3 test) gave an interview to UrologyWeek in which he talked about the real potential of this test. The following information is based on that interview.
The Basic Facts: The Progensa® PCA3 test approved in Europe is a gene-based diagnostic test. It may help to solve current challenges associated with the diagnosis of prostate cancer. The test requires only a urine sample as opposed to the blood sample required by the traditional PSA test. The test’s developers showed that the PCA3 gene is expressed in > 95 percent of prostate cancer tissue but is not expressed in normal or benign (non-malignant) prostate tissue in the same patients. This implies that PCA3 is not only prostate-specific, but also prostate cancer-specific.
Is the PCA3 Assay a Real Breakthrough? According to Prof. Schalken: “PSA is commonly elevated for reasons not related to cancer. As a result, PSA testing produces many ‘false positive’ results,” resulting in a high proportion of negative biopsies. (In the USA today, > 60 percent of all prostate buiopsies are negative.) Available data suggest that the PCA3 test has a specificity of over 80 percent, compared to a specificity of 25 percent for the PSA test. The PCA3 test also appears to be better than the PSA test at detecting aggressive forms of prostate cancer. However, the most compelling data will come from a screening trial that is still ongoing. This trial will compare the value of PCA3 tests with PSA tests directly. The results of this trial are expected this year (2009).
Can Any Laboratory Do This Test? The PCA3 assay “is a new and rather complex tool which should remain in the hands of experts for at least the first few years,” said Schalken. In Europe there are just eight laboratories that can perform the PCA3 test. “The tests are rather expensive and it takes qualified personnel to perform them. Thus, for reasons of quality, efficiency and costs it is best to have these tests done in specialised laboratories.”
What Will the PCA3 Assay Mean for Physicians? “We will be able to change to a more rational biopsy schedule,” said Schalken. “It is a first small step towards more individualized medicine. At present it is standard practice to take another biopsy when a patient has had a negative biopsy but a positive test and not to take another biopsy when the patient had a negative biopsy and a negative test. But when the biopsy is negative and the PCA3 is very high, the patient may well have a potentially lethal cancer.” Schalken added that we can expect positive PCA3 data followed by a negative biopsy to lead to careful imaging studies, allowing for identification of more cancers that are commonly located in the [front] of the prostate. He went on to say that the use of PCA3 in active surveillance and screening is currently under investigation. Depending on the results of these studies, we may see the expansion in use of the PCA3 test. (Some readers may remember that, in much the same manner, PSA testing was originally approved only to monitor patients receiving treatment for prostate cancer. It’s approval as a screening tool came later.)
And What Will the PCA3 Test Mean for Patients? Many patients “will no doubt actively seek PCA3 testing,” stated Schalken. “The more the patient is aware of the uncertainties surrounding the diagnosis prostate cancer, the more a test that gives more certainty is [going to be] welcomed. Patients will definitely try to avoid having to undergo a biopsy when it is unnecessary.” Schalken went on to speculate that in the future the family doctor would be able to order a PCA3 test. Most men already get their PSA test from their family doctor, who will then refer the patient to a urologist for a repeat PSA test and possible biopsy, but the family doctor is well aware that in many cases the biopsy will be negative and treatment will not be needed.
The Progensa PCA3 assay is being commercialized by Gen-Probe, a California-based company. Current information about the development of the PCA3 assay is available on a web site at www.pca3.org developed by Ismar Healthcare and underwritten with an unrestricted educational grant from Gen-Probe.
Despite the fact that the PCA3 test is not commercially approved for use in the diagnosis of prostate cancer in the USA, this web site lists several physicians in the USA who are able to offer the PCA3 test to patients. We assume that such access to this test is within the context of ongoing clinical trials, although this is not clear from the web site. This web site provides an extensive range of information on the development and use of the PSA test for patients and for physicians. For more information about access to the PCA3 test in the USA, please see also the article entitled “More on the PCA3 test.”
We have been unable to find any information suggesting when Gen-Probe expects the PCA3 test to be commercially available in the USA.