Two-gene DNA urine test for prostate cancer

In the current debate sparked by the recent USPSTF recommendation on PSA screening, it is clear that better biomarkers than PSA are urgently needed. One new biotechnology that may go a long way in detecting only prostate cancer and reducing unnecessary prostate cancer biopsies and possible subsequent overtreatment, is the development of a new urine test for prostate cancer. It was enabled by the discovery of specific prostate cancer DNA fusions in 2005 at the University of Michigan. This discovery opened the door to developing diagnostic tools that are specific only to prostate cancer.

Scott Tomlins, MD, PhD, a PCF Young Investigator funded in part by unrestricted funds from Safeway Foundation, and a team of researchers at the University of Michigan under the direction of Arul Chinnaiyan, MD, PhD, also a PCF Investigator, have developed a prostate cancer-specific test using two genetic fingerprints—biomarkers—that are prevalent in most prostate cancers and are easily detectable in a simple urine test. The DNA markers are the TMPRSS2:ERG gene fusion and PCA3 DNA. TMPRSS2:ERG occurs in 50 percent of prostate cancer patients. TMPRSS2:ERG and PCA3 DNA (prostate cancer antigen) are expressed at high levels in 95 percent of prostate cancers.

"With more than 300 types of human cancer, this two-gene DNA urine test is ultra-specific to prostate cancer and prostate cancer only," observed Jonathan W. Simons, MD, president and CEO of the Prostate Cancer Foundation. "PSA in the blood is not cancer specific, but this new DNA diagnostic tool is. Accelerating research on these types of new biotechnologies can help us get out of the 'ditch' in which the debate over the limited usefulness of PSA screening has mired us."

The availability of an easy-to-use urine test that is specific in identifying the presence of cancer has the potential to eliminate thousands of unnecessary prostate biopsies in the U.S. each year. Physicians currently begin recommending a biopsy, based on patient factors such as age, family history and general health, once a man's serum PSA levels rise above 4.0 ng/ml. Yet, less than half of the patients who are biopsied each year are subsequently diagnosed with cancer.

"There is no one biomarker for every prostate cancer," explains Dr. Tomlins. "But, by combining these two specific biomarkers that are widely found in prostate cancer patients, we now have a tool for making more informed decisions. Using this combined test, patients and their physicians can now decide to proceed to biopsy or delay a biopsy with greater confidence." The results of studies using the new urine test were published in Science Translational Medicine (www.ScienceTranslationalMedicine.org) by Dr. Tomlins and other researchers who are involved with the trials.

According to Dr. Tomlins, patients with low levels of TMPRSS2:ERG and PCA3 DNA markers have only a 20 percent chance of being diagnosed with prostate cancer and their chances of having a high-risk cancer are less than 10 percent. However, patients with high levels of these biomarkers have been shown to have an 80 percent chance of having cancer with a 50 percent risk of having high grade cancer. There is also an association between test results and the corresponding size of the tumor in patients who do have cancer.

There is also another benefit of this new test beyond identifying which patients really require biopsies. Needle biopsies can miss entire areas of the prostate in which cancer is present. In combination, this new biomarker test provides more data with which clinicians can home in on a patient's cancer and may allow for more effective assessment of the cancer's potential aggressiveness.

While it is important to note that it will take some time before the combined urine-based assay is widely introduced into practice, the University of Michigan has been offering the PCA3 test alone since earlier this year. They expect to be offering it in combination with TMPRSS2:ERG in 2012 under a license agreement with GenProbe. Another trial using the combined assay will soon be conducted in cooperation with the Early Detection Research Network (EDRN). EDRN, an initiative of the National Cancer Institute (NCI), brings together dozens of institutions to help accelerate the translation of biomarker information into clinical applications and to evaluate new ways of testing cancer in its earliest stages and for cancer risk.

Once the University of Michigan (U-M) begins offering the combined TMPRSS2:ERG/PCA3 test, physicians can send urine samples to U-M for analysis until the combined test is more widely available.