Johns Hopkins researchers say they have devised a more accurate blood test for prostate cancer that could eventually replace PSA screening, flagging more malignancies while reducing the number of false alarms.
The scientists, who reported their findings today in the journal Urology, say the test could spare thousands of men painful biopsies that turn out negative every year.
"We're biopsying a lot of men who don't have prostate cancer," said Dr. Robert H. Getzenberg, director of urological research at the Johns Hopkins Brady Urological Institute. "Now we may be able to save men from undergoing biopsies or unnecessary surgery."
Getzenberg said the test - which requires more study of its effectiveness - can also distinguish between cancers confined to the prostate and those that have invaded surrounding tissue.
Such information could help doctors and patients decide whether to begin treatment immediately, monitor the cancer's progress before treating it or forgo therapy altogether, he said.
The simple blood test looks for a protein called EPCA-2, which is produced only by the nuclei of cancerous prostate cells.
Getzenberg and seven colleagues tried the screening test on 385 men for the study but are also in the midst of larger trials. If successful, they could prepare the test for government approval 18 months from now.
Prostate cancer is the second leading cancer killer of men in the United States, accounting for more than 30,000 deaths annually, according to the American Cancer Society. Only lung cancer kills more.
A quarter-century ago, a blood test that looks for a protein called prostate-specific antigen (PSA) revolutionized the diagnosis of prostate cancer. Doctors finding elevated levels often recommend biopsies, painful tests in which a needle is inserted into the gland several times to withdraw tissue samples for analysis.
When biopsies turn up evidence of cancer, doctors often suggest the removal of the prostate.
Early warnings from PSA tests have resulted in skyrocketing numbers of prostate cancer diagnoses and a decline in the number of deaths.
But the tests have also proved controversial. The PSA is elevated not only in men with prostate cancer, but also in those with prostate infections or benign enlargement of the gland, a common condition. Critics have argued that the test is overused, leading to needless biopsies, surgery and radiation treatments.
In their clinical trial, the Hopkins doctors found that the new test misses few actual cancers and is far less likely to raise the specter of cancer in patients who are actually healthy.
Previous studies have shown that PSA tests flag about 85 percent of true cancers. The new test flagged 94 percent of cancers in the Hopkins trial - a difference that Getzenberg called "incremental."
The more important contrast is the rate of "false positives," elevated levels in patients who are actually free of cancer, he said.
"The first thing we want to do is get rid of the unnecessary biopsies," said Getzenberg. "We're now doing six biopsies to find one [cancer]. In the U.S., about 1.3 million men are going to undergo prostate cancer biopsy [in one year] to find about 230,000 who have prostate cancer."
Previous studies have found false-positive rates as high as 85 percent with PSA screenings. All told, 25 million men in the United States have had prostate biopsies that showed no evidence of cancer. In contrast, false positives occurred in only 3 percent of men with elevated EPCA-2, according to the Hopkins study.
The clinical trial also produced an unexpected result, he said. Mildly elevated levels of EPCA-2 indicated prostate cancer that was confined to the gland, while higher levels signaled cancer that had spread beyond the organ.
Learning that the cancer is confined can have a profound impact, he said. For some men, especially younger men, it may signal an ideal time to have the prostate surgically removed - before the cancer has spread.
Others may decide on a course of "active surveillance," postponing treatment while keeping a watchful eye for signs that the cancer threatens to break out.
The test has drawn a mixed reaction, with some experts hailing it as a significant step forward and others saying it still leaves important questions unanswered.
"A more accurate screening test will reduce the number of men who undergo needless biopsies and will increase the number of men who are diagnosed with prostate cancer," said Dr. Howard Parnes, chief of prostate and urological research in the National Cancer Institute's division of cancer prevention.
But, said Parnes, it could also lead to a larger number of men diagnosed and ultimately treated for slow-growing cancers that never would have caused problems in their lifetimes. No one has yet found biomarkers that can accurately forecast whether a man's prostate cancer will ultimately kill him.
"You may be able to identify people in whom a cure is possible," Parnes said. "But it doesn't tell you in which patients a cure is necessary. How many of those men don't need to be cured? How many were overdiagnosed?"
The questions, he said, are of more than academic interest. Despite surgical innovations, some patients are left impotent or unable to control their bladders. Radiation can cause bowel problems.
But Dr. J. Brantley Thrasher, a spokesman for the American Urological Association, said the test holds great promise. By reducing the number of false positives, the test answers the greatest shortcoming of the PSA test, he said.
Prostate cancer by the numbers
It kills about 30,000
1.3 million men undergo prostate cancer biopsy
230,000 found to have prostate cancer