A blood screening result that suggests prostate cancer is bound to provoke high anxiety - even though up to 80 percent of those findings turn out to be false positives.
Anxiety deepens, of course, if a biopsy confirms a cancer diagnosis, to the extent that many men demand surgery or radiation even when they don't need it.
Now, two national health panels have made startling recommendations that call into question the way doctors have been handling prostate cancer testing and treatment. One panel said men should skip standard prostate-specific antigen, or PSA, testing unless they have symptoms such as urinary blockage or pain. A second panel urged many men with low-risk prostate tumors to turn to "active surveillance" rather than immediate surgery or radiation.
The recommendations - the first is part of a draft report by the U.S. Preventive Services task force in October, the second came from a panel convened by the National Institutes of Health this month - have generated controversy, even as researchers work to develop better methods. "Skipping the PSA is the wrong way to approach it. It's an extreme viewpoint that will have terrible ramifications on public health if it goes forward," says Dr. Bruce Kava, interim chair of urology at the University of Miami Miller School of Medicine.
"I've had patients whose cancer was discovered by a PSA test," adds Dr. Rakesh Singal, a urologist and prostate cancer researcher at the University of Miami medical school.
The Preventive Services task force recommendation came after a months-long study of clinical trials around the world. "The common perception that PSA-based early detection of prostate cancer prolongs lives is not supported by the scientific evidence," the draft report said. The task force is a congressionally mandated panel of doctors, nurses and other specialists that develops recommendations for doctors and hospitals.
The second recommendation, from a "consensus panel" of 14 researchers and clinicians convened this month by the National Institutes of Health, tackled the treatment side: "Treatment of low-risk prostate cancer with radical prostatectomy or radiation therapy leads to side effects such as impotence and incontinence. Active surveillance has emerged as a viable option."
Responding to those concerns, researchers in South Florida and around the world are working on better screening tests to replace or at least supplement the PSA test, which has been use since 1986. Such improved tests could make the screening controversy "moot," the U.S. Cancer Foundation says. It says studies also are under way to better guide how aggressive treatment should be when cancer is confirmed.
The prostate, a small-plum-sized gland that sits above the base of the penis and helps produce semen, becomes enlarged in half of all men by age 60, and half of those will have symptoms such as frequent urination, weak stream or inability to completely empty the bladder.
And the symptoms raise the question: Is it benign prostate hyperplasia (enlargement) or prostate cancer? Cancer is not rare. One-third of men ages 40 to 60 and three-quarters of men older than 85 have prostate cancer, federal health officials say - even though most of it is microscopic and clinically insignificant.
Researchers say most of those diagnosed with prostate cancer are likely to grow old and die of something else first. The lifetime risk of death from prostate cancer is only 2.5 percent, and the median age of death from prostate cancer is 80, says the U.S. Centers for Disease Control and Prevention. Still, it's the second greatest cause of male cancer deaths after lung cancer, killing 32,000 men a year.
"We realize it's a dilemma," says Kava, the urologist, calling the number of positive PSA tests that lead to negative biopsies "unacceptably high. ... And biopsies are not innocuous. Some find them painful. Also, false positives can create anxiety, sometimes depression."
Biopsies also cause fever, infection, bleeding and transient urinary difficulty in 68 of every 1,000 procedures, the task force report says. Seeking to balance the benefits of the PSA test against the harms, the task force concluded that men without overt symptoms should skip the PSA tests.
Protest came quickly from the American Urological Association: "We are concerned that the task force's recommendations will ultimately do more harm than good," it said. "It is our feeling that, when interpreted appropriately, (the PSA test) provides important information in diagnosis."
Research at several U.S. universities soon might produce better screening tests to replace or supplement the PSA test, said the California-based Prostate Cancer Foundation, which raises funds for research. Foundation president Jonathan Simons said his group's 2011 annual Scientific Retreat heard presentations of 17 new tests under way that might improve on the PSA.
"The PSA debate can become moot with intensive and accelerated research that delivers a better test," he said.
One new test is being developed by Rakesh, the University of Miami urologist, and a team of researchers who say a DNA blood test may increase the accuracy of diagnosis when added to the PSA test.
"I think it can be very useful in helping decide whether to go on to a biopsy," he says.
The test needs funding for more study, but could be ready in a year or two, he says.
Another promising method, being developed at the University of Michigan Comprehensive Cancer Center by director Arul Chinnaiyan and his team, would use a two-gene DNA test they say is 80 percent accurate to detect prostate cancer. The study was published Aug. 3 in the peer-reviewed journal Science Translational Medicine. The university hopes to offer the test to its patients within a year and to the general public soon after.
But even if new tests improve upon the PSA, it still leaves the issue of treatment for confirmed cases. Anxiety can cause men to demand aggressive treatment even when they don't need it, the task force said.
"Over three quarters of men with localized prostate cancer undergo prostatectomy or radiation therapy," the task force report says. "Radiotherapy and surgery result in adverse effects, including urinary incontinence and erectile dysfunction, in at least 20 percent to 30 percent of men treated with these therapies."
Men with aggressive prostate cancers clearly need aggressive treatment, the task force says. But many others don't need such drastic measures: "Even when asymptomatic cancer is found by PSA, a majority of the tumors will progress so slowly that the man will die of something else."
The report notes there is "no consensus about the best treatment of localized disease."
Kava, the Sylvester urologist, says he has seen anxiety over PSA tests lead men to demand more aggressive treatment than they need.
"We try to temper their emotional response by giving them data," he says. "But we're a patient-driven practice. If they want therapy, we will go forward with it."
Kava says doctors increasingly are turning to two methods of tracking the progression of the cancers - "active surveillance" and "watchful waiting."
A major new active surveillance program funded in 2010 by $5 million from the Prostate Cancer Foundation is the National Proactive Surveillance Network, designed and run by Johns Hopkins University and Cedars-Sinai Medical Center in New York.Â
In the program, open to men across the country, local doctors do the testing and submit results to Johns Hopkins online. Men with PSA scores lower than 15 who have biopsy evidence of small-volume, low-grade cancer are examined and their PSA levels analyzed at six-month intervals, with annual biopsies. In the program's first year, only 32 percent of the men followed have progressed to where they need radiation or surgery.
The University of Miami Medical School and Sylvester have similar surveillance programs, Kava says, following more than 800 men with prostate cancer.
For older men and those in poor health from other causes, with life expectancies under 10 years, Kava says less-rigorous "watchful waiting" programs may be appropriate, with fewer biopsies and other intrusive procedures.
Meanwhile, Simons says his foundation is funding more studies into how doctors can identify which tumors need aggressive treatment and which don't. The University of Michigan search for a DNA test to supplement the PSA test also is designed to give better information about how aggressive the cancer is, based on tumor size and appearance under a microscope.
It comes down to this, Simons says: "Experts believe many prostate cancers will never cause a problem the rest of your life, even if you're diagnosed at 50. But others will kill you. We need to understand what makes one prostate cancer indolent while another is lethal.
"The overtreatment of prostate cancer will go away when we can look at a man and say, 'Mr. Jones, this cancer is a turtle, and this one is a shark.' We're a few years away."
How best to detect and treat it?
The gold-standard test for prostate cancer is the praised and vilified PSA test, a blood test that measures a protein that can signal prostate cancer. Or not. In men who got a routine PSA test even though they didn't have serious symptoms of pain or blood in the urine or semen, one study said the test found evidence of cancer in 25 percent. Indication of cancer was defined for purposes of that study as a PSA of 4.0 nanograms per milliliter or higher. But subsequent biopsies determined that 80 percent of those "positives" were false. (Higher PSAs are considered more likely to indicate cancer, although the National Cancer Institute says there is no specific normal or abnormal PSA level.)