OTIS BRAWLEY, MD, IS ADMITTEDLY A SKEPTIC OF THE MEDICAL SYSTEM. An African-American, he was raised among people who had a deep distrust of doctors and hospitals, believing they could cause as much harm as good.
And that is how Brawley has come to view screening for prostate cancer with the long-established blood test. He believes it causes as much — if not more — harm as good. It's an issue on which he has become a crusader.
Brawley, the medical director of the American Cancer Society, opposes routine, widespread screening using the prostate-specific antigen test, or PSA, as a way to detect prostate cancer in healthy men. He argues that men have been misled into believing that prostate cancer screening saves lives, when science has never definitively shown that to be the case. Rather, he believes large-scale PSA screening has resulted in great suffering from needless and potentially damaging treatments, with uncertain benefits.
Brawley is among the many health-care leaders calling attention to the problem of overscreening — not just for prostate cancer, but for conditions from breast cancer to heart disease — which adds billions of dollars to health-care costs annually. Screenings and the medical procedures that may result, such as biopsies following a high PSA reading, feed the U.S. medical spending juggernaut. The Institute of Medicine reported in September that $750 billion is wasted by the U.S. health-care system each year. Unneeded care amounts to $210 billion of that total.
Nonetheless, the PSA screening controversy, which has persisted for more than a decade, shows how dilemmas in medical practice can impede change.
OVERDOSING ON SCREENING?
Millions of men in the United States now take the PSA test, which measures the level of a protein produced by the prostate gland that can be an indicator of prostate cancer — the second-leading cause of cancer death for U.S. men. This year, it will take the lives of 28,000, estimates the American Cancer Society. A man's lifetime risk of dying of prostate cancer is 2.8 percent among Caucasians and 3.5 percent among African-Americans. The cancer society had recommended in 1993 that men receive a PSA blood test annually starting at age 50 — age 40 for African-Americans and others at higher risk — though it backed off in 1997, saying men should talk with their doctors first about the benefits and drawbacks of the test and make an informed decision before being screened.
A big limitation of the PSA test is that it is imprecise, unable to effectively distinguish between slow-growing, harmless cancers, which are most common, and more aggressive, deadly ones. And high levels sometimes don't indicate cancer at all, but instead more benign conditions such as an enlarged or inflamed prostate.
A high PSA result often leads men down a path to surgery, radiation or hormone therapy which may — or may not — be of benefit and which can have lifelong complications, including impotence, incontinence and problems of bowel control. Unfortunately, no better method for detecting potential prostate cancer exists. It has become entrenched in the medical care system, with many vested interests involved, including doctors, hospitals and pharmaceutical firms.
"Prostate cancer is a poster child for the problem of overdiagnosis," says H. Gilbert Welch, MD, MPH, with the Dartmouth Institute for Health Policy and Clinical Practice and author of Overdiagnosed: Making People Sick in the Pursuit of Health.
"We have done it for 20 years because some people thought it might save lives," says Brawley, professor of oncology and epidemiology at Emory University. "But we told people — we in medicine — that it saves lives and you should get it. My own American Cancer Society recommended every man over 50 get prostate cancer screening — every black man over 40 — back in 1993 without adequate scientific data. Everybody is so brainwashed into thinking that prostate screening is the right thing to do," adds Brawley, who has been both praised and vilified for his views on the highly divisive issue. (To be clear, however, he and other critics of the test endorse its use to track the growth of cancer once it has been identified.)
In a May article in the British Medical Journal, health journalist Ray Moynihan, a senior research fellow at Bond University in Australia, and two co-authors identified prostate cancer as one of a dozen commonly overdiagnosed conditions. The others included breast cancer, asthma, osteoporosis and attention deficit disorder, according to the researchers, who said medicine's ability to heal the sick is becoming overshadowed by its capacity to harm the healthy.
"Screening programmes are detecting early cancers that will never cause symptoms or death, sensitive diagnostic technologies identify 'abnormalities' so tiny that they will remain benign, while widening disease definitions mean people at ever lower risks receive medical labels and lifelong treatments that will fail to benefit many of them," the researchers write.
Next fall, the Dartmouth institute is hosting an international conference on the wider problem of overdiagnosis, partnering with Bond University, BMJ and Consumer Reports.
The costs to the system are enormous. In one study, published this April in theJournal of the American Medical Association, Donald Berwick, MD, former chief of the U.S. Centers for Medicare and Medicaid, and colleague Andrew Hackbarth of the Rand Corp. estimated that between $158 billion and $226 billion was wasted in 2011 in the United States on care that can't help patients, including some end-of-life care and surgical treatment when simple monitoring of a condition would have sufficed.
Americans have embraced the concept of medical screening in the belief that more knowledge is better, says internist Randall Stafford, MD, PhD, a professor of medicine at the Stanford Prevention Research Center who studies the adoption of disease prevention practices. But sometimes that knowledge sends patients down a path to more testing and more treatments, which are not only costly, but harmful.
"While some screening tests have limited utility, patients often expect that a full evaluation will include them, including an EKG, urinalysis or blood count," says Stafford. "We now recognize that there is tremendous overuse of those diagnostic tests."
The problem is that the tests not only cost money, but also can lead to more unneeded health-care activities. "An EKG that is suspicious for coronary artery disease leads to a stress test, which leads to a catheterization, which in turn leads to a bypass surgery, all of which might not have been necessary," says Stafford. "These tests are not specific. That is, a suspicious test result may not always represent actual disease."
Cancer screening is particularly controversial. In 2009, the U.S. Preventive Services Task Force set off a firestorm when it recommended women start getting routine mammograms at age 50, rather than 40, and switch from annual checks to every other year. The organization, which reviews the scientific justification for clinical preventive services, found evidence lacking for earlier and more frequent screenings.
When the decision came out during the national debate over President Obama's health-care reform legislation, opponents decried it as health-care rationing. Many physicians' groups also denounced it, as did some breast cancer research and treatment advocacy groups. Congress went on to undermine the recommendation by writing a requirement into the health-care reform law for insurers to cover mammograms for women ages 40 to 49 despite the task force's conclusion.
Then this spring, the task force added further fuel to the debate when it gave the PSA test a "D" rating and recommended against it for the general population. In its report, the panel noted that a large percentage of men who are screened opt for treatment, with various ill effects.
Among 1,000 men screened, as many as five will die within a month of prostate cancer surgery and between 10 and 70 will have serious complications, the panel reported. At least 20 to 30 percent of men undergoing radiation therapy or surgery will have long-term side effects, including urinary incontinence, erectile dysfunction and bowel dysfunction, while hormone therapy may lead to erectile dysfunction, breast enlargement and hot flashes, according to the report, published in May 2012 in theAnnals of Internal Medicine.
"Based on this work, the task force concludes that many men are harmed as a result of prostate cancer screening and few, if any, benefit," concludes the task force on its website.
AMERICANS HAVE EMBRACED THE CONCEPT OF MEDICAL SCREENING IN THE BELIEF THAT MORE KNOWLEDGE IS BETTER.
The recommendation provoked outrage in the urology community, with the American Academy of Urology calling it "inappropriate and irresponsible." The group notes prostate cancer mortality has significantly declined in the United States, which it believes is largely due to the advent of widespread PSA screening. In June, the American Medical Association voted to officially express concern over the task force's recommendations on both mammography and PSA testing.
"In the United States, death rates from prostate cancer have decreased by 40 percent, and the percentage of men who present with metastases has decreased by 80 percent," says Northwestern University urologist William Catalona, MD, a screening advocate whose early studies helped validate use of the test. "So we are detecting prostate cancer earlier and detecting it in a curable stage more often. Screening has fallen victim of its own success. Now we have people saying we are detecting it too early and treating it too often."
THE TEST'S HISTORY OF CONTROVERSY
Overdiagnosis' "poster child," the PSA, first came into vogue following a 1987 report in the New England Journal of Medicine by Stanford's Thomas Stamey, MD, now an emeritus professor of urology, which suggested it could be useful as a marker in the blood for the disease. Men rushed in, eager to know their status, leading to an immediate spike in prostate cancer diagnoses. These men would go on to have their prostates biopsied, with doctors sampling tissue though a needle from a dozen spots in the gland, which is about the size of a golf ball. Biopsies are not only uncomfortable, but can cause bleeding, infection and, in 1 percent of cases, hospitalization.
In those days, if any one bit of biopsied tissue came back positive, the patient would usually go on to have the entire organ removed, and possibly radiation therapy. Because the prostate is located deep in the pelvis, surrounded by other organs and hard to access, it is difficult for surgeons to avoid damaging the nerves that control vital functions, such as ejaculation and urination.
By 2004, Stamey himself began to question the test, saying it was turning up far too many cases of small, low-grade tumors that were unlikely to spread and cause any harm, yet were subjecting men to unwarranted treatment. His paper that year in the Journal of Urology highlighted a major flaw in the test — its inability to distinguish between slow-growing tumors that may never be troublesome and the more aggressive, potentially deadly ones. His conclusion, that the test was of limited value, caused a furor among urologists.
Two major studies have been completed since then, yet neither has been sufficient to settle the controversy.
A large U.S. study, known as the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, enrolled men at 10 centers around the country over six years. The results, published in January 2012 in the Journal of the National Cancer Institute, showed no difference in mortality among men in the screening group versus controls. Unfortunately, many men in the control group could not restrain themselves from being tested, so the results were considered contaminated.
A separate study, published in 2009 in the New England Journal of Medicine and involving 162,000 men in seven European countries, showed a 20 percent relative reduction in mortality among men receiving the test, though the authors noted that screening is associated with as much as a 50 percent risk of overdiagnosis. The study is often cited by patient advocates and others favoring PSA screening as clear evidence of the value of the test. In August, Dutch researchers published a follow-up to the European study, saying whether or not to screen depends on how an individual patient feels about the possible harms and benefits.
UNCOUPLE SCREENING AND TREATMENT
James Brooks, MD, a professor of urology at Stanford and prostate cancer expert, says a moratorium on testing, as recommended by the task force, is akin to "throwing the baby out with the bathwater." He still believes the PSA is useful, recommending annual tests for men ages 50 to 75.
"Elevated PSA is a marker of risk, much as high blood pressure is a marker of risk for death from heart disease," says Brooks, chief of urologic oncology at Stanford Hospital & Clinics.
He says the task force ignored the fact that death rates and the incidence of metastatic disease have significantly declined, with studies suggesting the decline is related to screening and treatment of localized disease and less so to improved treatments of advanced disease, as some critics argue.
He also believes the task force erred in directly linking screening to treatment. If, for instance, a man has a high PSA, he can go on to have a biopsy, and that may show that he has low-grade disease, in which case the cancer would just be monitored, not treated.
"We have learned that low-grade cancers can be watched safely. Because of that I uncouple screening and treatment. Men with low-risk cancer are watched, and men with aggressive cancer are treated," he says. "There are two randomized trials that show that operating on men with intermediate and high-risk cancers, rather than doing nothing, improves their life expectancy and decreases their chance of developing metastatic prostate cancer. Those are the patients to whom we offer treatment."
'PEOPLE ARE SCARED BECAUSE THEY HEAR THE WORD, "CANCER." DOCTORS ARE SCARED BECAUSE THEY HEAR THE WORD "CANCER." TOGETHER THIS PROMPTS TREATMENT.'
At the core of the problem with PSA screening is the fear inflamed by a diagnosis of cancer. "People are scared because they hear the word 'cancer.' Doctors are scared because they hear the word 'cancer.' Together this prompts treatment. It does not help that there are monetary incentives that drive those decisions," says Brooks.
Brawley, who recently authored the book How We Do Harm: A Doctor Breaks Ranks about Being Sick in America, says he is particularly concerned about free mass screenings at county fairs, shopping malls, churches and other public venues that are sponsored by special interests seeking to attract new patients but that don't provide men the opportunity to make informed decisions. (One past sponsor has been Kimberly Clark, the maker of Depend diapers for adults, he notes.)
"There's a lot of publicity out there — some of it by people who want to make money by recruiting patients — that oversimplifies the issue by saying that prostate cancer screening clearly saves lives. The truth is if you are concerned about prostate cancer, understand there are proven risks and possible benefits.... Every man needs to decide for himself," says Brawley.
LIVING WITH UNCERTAINTY
Often the first reaction among men is to have the cancer removed until they learn about the serious side effects surgery can cause, Brooks says. Once he describes them, he says, many become open to the idea of active surveillance, in which they are monitored with periodic PSA tests, biopsies and physical exams.
"In 1997, virtually all of our patients who were diagnosed, even if the tumor was small and low-grade, got an operation," he says. "Now, one-third of those patients are in active surveillance."
Bill, a 70-year-old Oakland, Calif., resident, is one such patient. Since 2002, he had been getting annual PSA tests, and while the numbers bounced around, they showed a gradual upward trend. So in 2008, at the suggestion of a Berkeley, Calif., urologist, he had a prostate biopsy, which detected something suspicious. The urologist then launched into a discussion of his various treatment options. "My mind said that if I had some kind of cancer, I want to take care of this. This was based on ignorance," says Bill, who asked that his last name not be used to protect his privacy.
He went home and talked to his wife and then began asking more questions of his urologist. "We started talking about side effects — impotence and incontinence, that sort of thing. I kind of felt I was getting different stories at different times."
He decided to get a second opinion and came to Stanford, where he learned that he actually had very little, very low-grade cancer and was a good candidate for active surveillance. Brooks has continued to measure his PSA levels quarterly and do a biopsy every 18 months. Bill's PSA has been trending down.
"On the whole, I'm glad I'm getting the PSAs, and I'm glad I didn't rush into treatment because there are lots of side effects from the treatment," he says. "The cancer is small and doesn't cause me any problems. Treatment would probably cause more problems than having the cancer. So I'm really feeling good about the decision."
THE NEW ATTITUDE
While the PSA test remains widely used, medical associations, including the American College of Physicians and the American College of Preventive Medicine, have begun to advise caution, saying men need to have a detailed conversation with their doctors before proceeding with the test and possible follow-up treatment. Even the conservative American Academy of Urology, in its 2009 Best Practice statement, recommends that men be informed of the risks of screening and of the option of active surveillance for newly diagnosed patients; the organization is currently revising its guidelines to reflect the state of the science.
Which begs the question, what is the state of the science? One unfortunate aspect of the debate over the PSA test is that valuable time has been lost, when scientists could have been looking for other alternatives, Brawley says.
"The urologic industry has been so fixated that they've delayed finding something better than PSA. So what's a man to do since we've been so foolish," he asks.
In fact, efforts are now under way to find a better option, with researchers using genomics, new imaging techniques and other strategies to develop more reliable indicators of the disease. Brooks is involved in several of these studies, including one in which 700 men are under active surveillance, undergoing periodic testing in an effort to develop a marker that can distinguish aggressive tumors from non-aggressive ones.
In another study, he is collaborating with Sanjiv Sam Gambhir, MD, PhD, professor and chair of radiology at Stanford, in using nanotechnology to measure proteins in the blood that may be better indicators of the disease than PSA. And at least two Bay Area companies have alternatives in clinical studies that aim to single out those cancers most likely to progress and require treatment.
"There are certainly plenty of men who are getting treated who don't need to be," says Brooks. "So we have to move the ball down the field. We just need better tests."
