Aug. 3, 2011 -- A painless urine test could soon help doctors tell when a high prostate-specific antigen (PSA) level means a dangerous cancer or when it’s a sign of a more benign condition that may not need further treatment, a new study shows.
The test looks for a genetic mistake that’s present in about half of all cases of prostate cancer.
This mistake, a case of two genes that come together and fuse, doesn’t appear to occur anywhere else in the body, or even in precancerous conditions, making it a highly specific marker for the disease.
When the genes fuse, says study researcher Scott A. Tomlins, MD, PhD, a pathologist at the University of Michigan Health System, in Ann Arbor, it’s a lot like flipping a switch. “And that gene, when it’s turned on, can cause cancer.”
Refining PSA Test Results
“This would be done for men who have been identified as having an elevated PSA,” Tomlins says.
Currently, doctors are split over the value of PSA testing for prostate cancer. That’s because PSA can be elevated even when cancer is not present, for example, when the prostate is inflamed, as in the case of prostatitis, or enlarged, as in benign prostatic hyperplasia (BPH).
Yet high PSA levels, over four, typically lead to a biopsy, which can cause discomfort, anxiety, and in rare cases, lead to complications like infections. Biopsies are also expensive, costing somewhere between $500 and $1,500. Researchers say that right now, when PSA levels are elevated, it’s up to patients and their doctors to figure out what to do next.
“There really aren’t very good tools to utilize to help make that decision,” Tomlins says. “We wanted to see if our urine markers could be useful in that situation.”
Testing for Prostate Cancer Biomarkers
For the study, which is published in the journal Science Translational Medicine, researchers tested the urine of 1,312 men with elevated PSA levels who had gone on to have needle biopsies or surgery to remove their prostates.
The test uses strands of artificially created oligonucleotides, the building blocks of DNA and RNA, which are built to match the code of the fused gene, which is called TMPRSS2:ERG.
To increase the accuracy of the test, researchers also looked for another gene, called prostate cancer antigen 3, or PCA3, which is also found in urine.
The two tests together appeared to generate both sensitive and specific results. Sensitive means it’s unlikely that the test would miss a case of cancer. Specific means that the test is unlikely to be positive if cancer isn’t really present.
Based on the levels of PCA3 and TMPRSS2:ERG detected, the men were given numerical scores that were classified as being high, medium, or low.
Those scores were then compared to the biopsy results.
“The men in the highest group have a risk of cancer on biopsy of about 70% and those in the lowest group have a risk of cancer of about 20%,” says Tomlins.
Researchers then narrowed their analysis to see how the urine test scores matched the men’s Gleason score, which helps doctors gauge how aggressive a cancer may be.
“What we’ve found is that your risk of having an aggressive cancer if you’re in the high group is about 40%, and if you’re in the low group, the risk of having an aggressive cancer is only about 7%,” Tomlins says.
The company that developed the test, Gen-Probe, helped to pay for the study, and several authors said they had a personal financial interest in the technology.
“This is great science,” says J. Stephen Jones, MD, chairman of the department of regional urology at the Cleveland Clinic in Ohio.
Now that the researchers have validated the test, further studies in larger, more diverse populations will be important to understand how it is best used.
“The real key is using this or any test to help drive decisions,” says Jones, who was not involved in the research, “If it helps me to know who to biopsy or not biopsy, that’s massively valuable information.”