Prostate cancer is the second leading cause of cancer death in men, occurring mostly in older men. Until the 1990’s, it was usually detected by physicians when performing a rectal examination, or after it had spread to other organs and was no longer curable. In the 1990’s, the first blood test to help identify prostate cancer, called Prostate Specific Antigen (PSA), was introduced. While this test is now widely used, and has helped to pick up cancers that were not detected before, it has limitations. First, many men with early prostate cancer do not have increased blood levels. Secondly, as men get older, other prostate diseases, such as benign prostate hyperplasia (BPH), can develop and cause an increased PSA level. While other tests that measure only certain forms of PSA (such as free PSA) can help evaluate high PSA levels, a man and his doctor are often unsure of how to use the results of these tests in deciding on whether to perform biopsies.

These facts have led to searches for more specific and sensitive markers of prostate cancer that may improve detection of early cancer and that may be less likely to be elevated in BPH or other non-cancerous prostate diseases. A recent study from researchers at Johns Hopkins University in Baltimore describes a new test that, in early studies, has some features that suggest it might address some of the concerns that exist about PSA tests.

The study describes a newly discovered marker, called early prostate cancer antigen 2 (EPCA-2). The authors developed a test to measure EPCA-2 levels in the blood and studied it in men with and without prostate cancer. EPCA-2 was positive in over 90% of men with prostate cancer, including some who had normal PSA, and identified more cancers than did the PSA test. Among men with BPH, EPCA-2 was increased in 22%, but directly comparable data were not provided for PSA measurements. However, among all men without prostate cancer, more men had increased PSA than increased EPCA-2.

As with most cancers, the chance of cure is greatest if prostate cancer is detected early and before it has spread or metastasized to other organs. In this study, EPCA-2 levels tended to be higher in men whose cancers had spread beyond the prostate. The authors presented some data to suggest that EPCA-2 worked better than did PSA for determining whether the cancer had spread, but the differences were small and further studies will be needed to tell whether the new test is actually better for this purpose.

One additional and very important use of PSA is to determine whether there is any cancer remaining after surgery is performed. Generally, PSA levels that are below the lowest amount that can be measured (usually < 0.1 ng/mL) are considered evidence that the cancer has been eliminated. In a small group of 10 men who had undergone surgery, PSA fell to undetectable levels in all, while EPCA-2 was still measurable in all. There was a much smaller decrease in EPCA-2 than was true for PSA. No further information was provided on these patients, so it is difficult to tell whether PSA or EPCA-2 was providing more correct information on whether all of the cancer had been removed.

What do the results mean?

The study conducted by the Hopkins researchers is very preliminary, and a test that could be used routinely is at least 18 months away. The number of men with cancer who participated in the study was small, and the authors of the study point out that additional studies are needed. The authors also note that there was no evaluation of whether the test would be useful in place of PSA in routine testing of older men for prostate cancer. However, if these preliminary results hold true in larger clinical trials, then EPCA-2 may be a significant improvement over PSA in deciding whether to do biopsies. The fact that EPCA-2 was still measurable after prostate cancer surgery (at levels seen in women and in men without prostate cancer), even though PSA was not, might mean that EPCA-2 is produced by tissues other than the prostate and may not be as helpful as PSA in that setting. It is not possible, however, to draw conclusions without further evaluation of what measurable EPCA-2 levels mean over time because it may be a sign that cancer is still present. It is hoped that with further research we will be able to tell whether EPCA-2 actually represents a useful new tool for evaluating men for the presence of prostate cancer and whether it should be used in addition to or instead of PSA.

Source

Leman ES, Cannon GW, Trock BJ, et al.: EPCA-2: a highly specific serum marker for prostate cancer. Urology 2007;69:714-20.