A recent paper from Johns Hopkins suggests that a second specific epitope of “early prostate cancer antigen 2″ (EPCA-2) has a very high sensitivity and specificity for the detection of prostate cancer. This may represent a major step forward.
First, so as to be clear, let’s make sure readers understand what an “epitope” is. An epitope on a molecule such as a protein or enzyme or antigen is a very specific domain (region) of that molecule that stimulates the production of, and is recognized by, a very specific antibody. Each epitope on a molecule elicits the synthesis of a different antibody. So — in the context of this paper — the EPCA-2.22 and EPCA-2.19 epitopes are two different areas of the EPCA-2 molecule, and they can be tested for carefully selected properties.
There is a good background article on the development of the EPCA-2 assay on the Johns Hopkins Health Alerts web site.
The new paper by Leman et al. starts by reminding us that EPCA-2 was already known to be a highly specific and sensitive serum marker for prostate cancer (based on data from the epitope EPCA-2.22). It then goes on to report on an evaluation of the sensitivity and specificity of the epitope known as EPCA-2.19 in the detection of prostate cancer in a non-screening population of patients.
So what did the authors actually do?
They took 328 serum samples from men with PSA values both below and above 2.5 ng/ml who fell into one of several categories:
- Men who had had negative prostate biopsies
- Men with benign prostatic hyperplasia (BPH)
- Men with organ-confined and non-organ-confined prostate cancer
- Control populations
The serum samples from these men were then all tested using the EPCA-2.19 assay, with the following results, based on the premise that an EPCA 2.19 level of ≥ 0.5 ng/ml was a postive signal for prostate cancer:
- EPCA-2.19 had a specificity of 94 percent and a sensitivity of 91 percent in separating normal men and men with BPH from those with prostate cancer.
- So-called ROC analysis of the EPCA-2.19 assay showed an area under the curve of 0.982 (95% CI 0.952-0.996, P < 0.0001), which suggests a very high degree of accuracy of this test.
Clearly this study confirms the high potential of EPCA-2 as a diagnostic test for prostate cancer that is way more specific than the PSA test or even the PCA3 test (based on the data currently available). As the authors themselves note, however, “larger multi-institutional studies still need to be performed” and these studies will need to actually compare the accuracy of the EPCA-2 test to PSA (and perhaps PCA3) in prospective manner.
What is not evident yet is whether EPCA-2 or its epitopes can help us to distinguish between indolent and non-indolent forms of disease. It will be a step in the right direction if EPCA-2 helps us to be able to avoid thousands of unnecessary biopsies each year in men at almost no risk for prostate cancer, but we still need tests that can help us to discriminate between patients who do and don’t really need invasive treatment.
Filed under: Diagnosis Tagged: | Diagnosis, early prostate cancer antigen, EPCA-2
Search for new and
ongoing trials on the
CTAG PCa web site
It will be interesting to see how long it takes this test to come to market in light of its threatening elimination of 75-80% of a billion dollar a year prostate biopsy business.
PCA3 FDA study has started and take less than a year to complete.
Update on EPCA-2
http://pittsburghlive.com/x/pittsburghtrib/news/s_641304.html
Where is this test available and what is the cost? Will my Tricare insurance pay for this??
Dear Mr. Coppock:
The EPCA-2 test is not commercially available at this time (as far as we are aware). The test is still in development.
It MAY be possible to get this test done through the research team at Johns Hopkins in Baltimore, but I do not think that your Tricare insurance would pay for this.
Besides the recent lawsuit pointed to by Frank Patti above, there are other reasons to worry (perhaps).
The 2007 paper about it was in Urology. 2007;69:714-20. A fairly famous protein expert, E. P. Diamandis, questioned the findings later the same year in Clin Biochem. 2007;40:1437-9. One very simple question was, “What gene makes that protein?”, but there were several other reasons given for being skeptical.
The new Leman paper [for reference see main article above] doesn’t tell us the gene, and doesn’t tell us the sequences of the protein or of the epitopes used to make the antibodies. That’s not typical. Hope I’m wrong and that they really have a great marker that will be instrumental for screening. We need independent studies, but that might require knowing what is being measured.
A semi-recent review: (“Emerging biomarkers for the diagnosis and prognosis of prostate cancer”) is published in Clin Chem. 2008;54:1951-60.
When would the EPCA-2 test be available?
Commercially: If and when it is actually proven to be accurate — which could take years.
As a research tool: It is probably available now at selected academic medical centers.
Today’s date is June 26, 2010. Has there been any advancement on EPCA-2? What laboratories are involved in testing EPCA-2 and is it available in Puerto Rico?
As of June 27, 2010, as far as we are aware, there has been no significant progress on the development of EPCA-2, and we are not aware of any laboratories in Puerto Rico that can offer this test. Indeed, the only laboratory capable of carrying out this test at this time is probably at Johns Hopkins University in Baltimore — if they are legally allowed to do so.
Where can I get a EPCA-2 prostate cancer test in the U.S.A.
Dear Mr. Myers:
As far as I am aware there is no way to get an EPCA-2 test anywhere in the USA at the present time loutside of a research laboratory.
Are there any other blood tests that have shown more accuracy than the PSA
The PCA3 test appears to be slightly more specific for prostate cancer than the PSA test, but not to an extent that makes it any vast improvement.
At this time there is still no good blood or urine test that can help a man to understand he is at risk for clinically significant (as opposed to indolent) prostate cancer.
How useful is the free PSA test (ratio of free to bound PSA) test in estimating the risk for clinically significant (as opposed to indolent) prostate cancer?
PSA data of any type are not particularly helpful on their own in establishing risk for clinically significant as opposed to indolent disease. The value of the %free PSA test is in establishing the need for a biopsy, which may then give additional data (most particularly the Gleason score) which — in combination with other data — helps to establish whether the patient has low-, intermediate-, or high-risk prostate cancer.
I have performed a lot of biopsies. Looking for a good alternative for screening.
John: Men who have had multiple negative biopsies are rarely found to have prostate cancer. It seems likely that if you have an elevated PSA it is for reasons quite different from prostate cancer.
Reading all the stories I came across the magnetic resonance imaging spectroscopy for prostate cancer detection. Would not this be a very good way to confirm prostate cancer than the biopsy?
Yes Roy … It would … if it was as accurate as the biopsy …
Unfortunately, as yet, no form of MRI or other imaging technique has demonstrated that it is as accurate as prostate biopsy in determining (a) the actual presence of cancer foci or (b) the Gleason grades of individual foci of cancer. Both of these factors need to be known with the greatest possible accuracy in order to make the best possible decisions about the need for — and the appropriate types of — therapeutic intervention that could be applied.