STANFORD -- More than two-thirds of the men who test positive on the prostate-specific
antigen (PSA) test don't have cancer but they have to undergo a needle
biopsy of the prostate to find out for sure. Now, researchers have taken
the first step toward eliminating the need for most of those biopsies.
The group, led by Stanford urology professor Dr. Thomas Stamey, will describe potential ways to reduce the PSA test's false-positive rate on Tuesday, May 7 at the American Urological Association's annual meeting, in Orlando, Fla.
Generally, a PSA level greater than 4 billionths of a gram per milliliter of blood is considered suggestive of prostate cancer. However, 68 percent of men with PSA levels greater than 4 do not have cancer, said Stamey. He estimates that at least 90 percent of these false positives are due to benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate.
The most striking and cost-effective prospect for reducing false positives hinges on an identifying characteristic of BPH, Stamey's team reports. Normally, prostate-specific antigen is found in semen, but Dr. John McNeal, a clinical senior research scientist at Stanford University School of Medicine discovered a way to extract PSA directly from the prostate enlargements caused by BPH. Senior research associate Dr. Zuxiong Chen isolated this PSA, purified it and showed that it differs from most of the PSA found in semen.
"The PSA protein for BPH is similar to regular PSA, but there is a cleavage inside the molecule. It's nicked," said Chen, lead author of the BPH PSA research report. "It's not an intact molecule; a disulfide bond links it together."
The next step for the Stanford researchers will be to inject the newly isolated PSA into a mouse to try to obtain a monoclonal antibody against the substance. If the Stanford group is successful, this will yield a new PSA test that can distinguish cases in which high PSA levels are due to benign prostate enlargement rather than cancer, Stamey said.
"Men with BPH would not have to be biopsied if we could identify them on the PSA test," Stamey said.
Chen's paper is one of 10 the Stanford team will present at this week's meeting.
In another study, the team used a computer to analyze combined results from five prostate cancer markers in addition to PSA. Using this method as a diagnostic aid reduced the false-positive rate from 68 percent to 15 percent, reports Stamey.
Other studies focused on developing better treatment strategies. For example, complete removal of the prostate gland fails to eliminate the cancer in about 38 percent of cases, Stamey said. Researchers led by Dr. Michael Gong, chief resident in urology at Stanford University Hospital, found that while subsequent radiation treatments apparently could cure about 28 percent of these men with residual cancer, the apparent cure rate jumped to 71 percent when radiation treatments were combined with six months of combined androgen deprivation therapy.
Another study looked at men with prostate cancers larger than 12 cubic centimeters. Stamey's group was able to identify prognostic markers for deciding whether or not these men were likely to benefit from surgery to remove the tumor. Surgery eliminates the cancer in only 3 to 6 percent of such patients, Stamey said. Using information from the PSA test, digital rectal examinations, and prostate biopsies, Dr. Gregory Cost, a resident at Stanford University Hospital, put together a prediction model identifying 86 percent of those who would not benefit from prostate surgery.
"All of these [new papers] are interrelated," Stamey said. "We are trying to improve the diagnosis of prostate cancer and the ability to decide who should be treated and who should not."