Prostate cancer treatment misused

Androgen deprivation therapy (ADT) is prescribed inappropriately for many men in the early stages of prostate cancer and is associated with an increased risk of cardiovascular disease and diabetes. This was shown in a new study of over 37,000 men treated at the early stages of prostate cancer in the Veterans Healthcare Administration between 2001 and 2005. Published in a recent issue of the Journal of the National Cancer Institute, the study raises questions about informed consent and how much information men are given about ADT beforehand. There is no proof that it can prolong life or help men with low-risk, early-stage disease, yet ADT can cause severe adverse effects because it is drug-induced castration.

The research team led by Nancy L. Keating, MD, Brigham and Women’s Hospital, Boston, found that the high risks of diabetes (25%) and cardiovascular disease (20%) were associated with the gonadotropin-releasing hormone (GnRH) agonists. The drugs, sold under the brand names of Lupron and Zoladex, are injected by a physician or implanted under the skin every few months. No increased risk of diabetes and cardiovascular disease was associated with oral anti-androgen drugs like Euflex and Casodex, which are usuallly given in conjunction with GnRH agonists or, rarely, by themselves.

The increased use of ADT was linked to widespread screening with the PSA (prostate-specific antigen) blood test in a hard-hitting editorial that accompanied the VA study. The author, Peter C. Albertsen, MD, Department of Surgery, University of Connecticut Health Center, Farmington, states that the VA study offers a rare glimpse into the extent of ADT usage. He went on to note that PSA screening has dramatically changed the type of patient newly diagnosed with prostate cancer. “Before the advent of PSA screening, physicians used ADT to relieve symptoms of advanced prostate cancer. Now we use ADT primarily to treat patients with a rising level of PSA.” And most tellingly, Dr. Petersen writes, “We do not know whether these treatments [ADT] have prolonged survival, but [this study] confirms that this approach has the potential for substantial unintended side effects.”

Hot flashes, weakness, fatigue, cognitive impairment, and depression are the “substantial unintended side effects” of ADT, aka chemical castration. The VA study is not the first to link ADT to an increased risk of diabetes and cardiovascular disease, but it shines a light on unproven uses of this drastic therapy. The study shows that ADT is often given as the primary treatment for men with local and regional prostate cancer who have no symptoms of the disease, as well as symptomless men whose post-treatment PSA test show rising levels. The increased use of ADT can be chalked up to the fact that the PSA screening test was introduced in the late 1980s. This is well before the benefit of finding prostate cancer before symptoms appear was proven to reduce a man’s chances of dying from prostate cancer. See results of two recent clinical trials that explored this important question.

Dr. Keating, the lead author of the VA study, was asked to identify the men with prostate cancer for whom the proven benefits of ADT outweigh its considerable risks. “There are proven benefits to ADT for men with symptomatic metastatic prostate cancer in terms of controlling the spread of the disease which causes symptoms such as bone pain and fractures,” answered Dr. Keating in an e-mail, “and [there is] also a survival benefit to ADT when used as adjuvant [additional] therapy for men with high-grade disease, which is localized disease with high-risk features that make it more likely to return after primary treatment [with surgery or radiation therapy].”

And for whom is ADT most likely to be questionable? “The concern is that many men are treated with ADT for indications where there have never been studies showing benefit (e.g., as a primary treatment of prostate cancer and as a preventive against recurrence in those whose PSA levels rise after primary treatment). In these settings, the risks may outweigh any benefits,” answered Dr. Keating. “I think this has become a popular treatment because patients and doctors like the idea of doing something to treat the cancer. But the problem is, it has never been studied, and may have substantial adverse effects.”

So has the PSA screening test saved at least some lives? Apparently not, according to editorialist Dr. Petersen, who compared the current prostate cancer death rate with that of the era when men were not diagnosed with prostate cancer until they noticed symptoms. “Before the widespread use of PSA screening, an American man had an 8.7% lifetime risk of being diagnosed with prostate cancer and 2.5% risk of dying from this disease. By 2005, the lifetime risk of being diagnosed had increased to 17%, whereas the lifetime risk of dying from prostate cancer remained virtually unchanged.”

Maryann Napoli, Center for Medical Consumers(c)

Just Say No to the PSA Prostate Cancer Test

“Studies Fail to Settle Prostate Screening Debate” (Boston Globe);
“Prostate Screening Saves Lives” (BBC). 
“Prostate Cancer Screening May Not Reduce Deaths” (Washington Post).

These are just some of the headlines for the big health story last month about the PSA (prostate-specific antigen) screening blood test.  The results from two long awaited clinical trials were released early and simultaneously by The New England Journal of Medicine on March 18.  Despite the seemingly conflicting messages of these sample headlines, it is now clear that symptomless men should consider refusing this test.

The larger of the two trials was conducted in several European countries.  It found that the lifesaving benefit of PSA screening is far more modest than previously thought…and the risk of harm is very high.  For every 1,400 men who regularly had a PSA screening test over the ten-year period of the European trial, one man avoided death from prostate cancer and 47 men were treated unnecessarily for a cancer that did not progress.  The risks of treatment include urinary incontinence, bowel problems, and impotence.  Otis W. Brawley, MD, chief medical officer of the American Cancer Society, summed up the findings this way: “The test is about 50 times more likely to ruin your life than it is to save your life.”  (Click here for Treatment for Early Prostate Cancer.)

The other trial was U.S. government-funded and, unlike the European trial, it showed no reduction in prostate cancer deaths. The predictable and disturbing finding from both trials is this—many more prostate cancers were diagnosed in the men who were screened with the PSA test than in those who were not.  Few men opt for the “wait and see” approach once a PSA test, biopsy and other tests indicate the presence of cancer.

The debate over the PSA test is expected to continue, largely because flaws can be found in virtually all trials.  For example, the U.S. trial had less than half the number of participants of the European trial (162,000), which some believe may account for the absence of a lifesaving benefit.  In the U.S. trial, men were randomly assigned to annual PSA tests plus a digital rectal examination (screened group) OR what is known as usual care.

Given the fact that the PSA test has been aggressively marketed as a lifesaving test to doctors and the general public for the last 20 years, usual care in the U.S. involves a doctor recommending a PSA test. It is considered unethical to ask men in the unscreened control group not to have a PSA, and a large portion of them in the U.S. trial—38% to 52%—had the test.  Western European countries put up barriers to the marketing of an unproven test to the public.  In the U.S., most men over age 50 have regular PSA tests; in the U.K., where the National Health Service does not recommend PSA testing, only about 6% of men have had a PSA test because they requested one.

Treatment-Related Deaths?
There was a troubling finding from the U.S. trial that did not get media attention last month—it involves the deaths from the prostate cancer treatment itself.  When the authors of this trial looked solely at the participants who had been diagnosed with prostate cancer in the 10-year period of the trial, there were 312 men in the PSA screening group and 225 men in the unscreened control group who had died from causes other than prostate cancer.  The unexpectedly higher number of deaths in the screened group, say the authors, is “possibly” related to treatment of non-progressive cancer.

The question that no one seems to be asking at this time is: Why was the PSA screening test allowed to become so widespread when it cannot identify which prostate cancers are aggressive and lethal?  And no test currently exists that can make that distinction accurately.

Cancer screening tests are approved by the FDA on the basis of an outdated understanding of cancer, i.e. all cancers are deadly; finding cancer early is always good.; treatments are more effective with early diagnosis. All a company has to do is prove its product can find symptomless cancers.  The success of any screening test, however, should based on how many deaths can be avoided.  And most important, the chance of avoiding death should be far greater than the chance of serious harm as a result of the test itself.  The PSA screening test fails on both counts.

What to do:

• Inform yourself. Try to get as much information about prostate cancer, early detection, and the PSA test from sources other than hospitals and doctors who treat prostate cancer.  The National Cancer Institute is one place to start (www.cancer.gov).
• Be aware of the fact that some men are given the PSA test without their knowledge.  It is often automatically added in with the standard blood test for cholesterol, etc.  If you decide to forego a PSA test, make your wishes known before you are given a blood test.
• Recognize that fear-mongering with statistics is essential to cancer screening promotion.  Prostate cancer may in fact be the second leading cause of cancer death in men, but it accounts for only 3% of all deaths.  No prostate screening campaign is likely to flip that statistic around to tell men that 97% of them will not die of prostate cancer.  And the 20% reduction in prostate cancer deaths shown in the PSA screened group in the European study.  Here’s what it means: The man who regularly has a PSA test over the course of the next ten years will reduce his risk of dying of prostate cancer from 3% to 2.4%.

Maryann Napoli, Center for Medical Consumers© April 2009

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Treatment for Early Prostate Cancer

Not Better Than “Wait & See” Approach

A common treatment given to men with early-stage prostate cancer—one that has significant harms—was found to be no more effective in extending life than the “wait-and-see” approach. The study, published last summer in the Journal of the American Medical Association, highlights the fact that doctors have been using this treatment for decades without proof of benefit. Its finding became the centerpiece for an unusual article in a recent issue of the Journal of the National Cancer Institute that candidly discussed the many reasons for overuse, chief among them are the financial incentives that encourage treatment…but more on that later.

The treatment in question is called androgen deprivation therapy (ADT), aka drugs that shut off the male hormones known to promote tumor growth. It is given to men whose cancer is confined to the prostate and received no other treatment, such as surgical removal of the prostate. The 2008 study that showed ADT does not increase survival was conducted by Grace L. Lu-Yao, MPH, PhD, University of Medicine and Dentistry of New Jersey, and colleagues who drew their information from Medicare claims.

The men in this study were diagnosed with localized prostate cancer in 1992-2002. They were age 66 years and older at the time of diagnosis with a median age of 77 years. Survival results favored the untreated. During the ten year follow-up period, those given ADT had a lower prostate-cancer survival rate (80%) than those not given ADT (82.6%).

Wide variations were seen in the treatment duration—half of the ADT-treated stayed on the drugs more than 30 months. Such long-term use has been associated with 10% to 50% increases in the risks of fracture, diabetes, coronary artery disease, heart attack and sudden cardiac death, according to Dr. Lu-Yao and colleagues. Hot flashes and swollen breasts are some of the common adverse effects.

This is not the first study to show ADT for early-stage disease did not prolong life, though its use steadily increased over the last 20 years. In a telephone interview Peter C. Albertsen, MD, a co-author of the ADT study, acknowledged a trial that randomly assigned men to ADT or no treatment would be ideal. But that type of trial would have taken too long, he continued, “So we did the best we could by going to the Medicare claims data.”

Dr. Albertsen, who is a professor and chief of urology at University of Connecticut, Farmington, went on to explain, “It was thought that early use of ADT would offer a longevity benefit, but our analysis is convincing that early use of hormone therapy doesn’t make sense. In fact it makes much more sense to wait for the patients to develop symptoms before they are offered this treatment.”

That conclusion also calls into question the current practice of giving the PSA (prostate-specific antigen) blood test to symptom-free men, as part of a routine physical exam, though the test has yet to be proven life-saving. And many experts suspect that it causes far more harm than good, particularly in elderly men, because it leads to unnecessary drastic treatments [e.g., prostatectomy] for cancers that would never produce symptoms or become lethal. Furthermore, there is no accurate way to distinguish the cancers that will progress from those that will remain dormant for a lifetime. These concerns led to new recommendations from the U.S. Preventive Services Task Force.

Last summer, the USPSTF announced that men over the age of 75 years should no longer be screened for prostate cancer and men younger than 75 years should know “the benefits of screening for prostate cancer are uncertain and the balance of benefits and harms cannot be determined.” With this recommendation, the USPSTF parts company with many other medical organizations like the American Urological Association that recommend PSA testing for all men after the age of 50 years.

With the new USPSTF recommendation in mind, Dr. Albertsen was asked whether it is reasonable to see his study’s findings as an example of the harm that results from the aggressive promotion of the PSA test over the last 20 years. “Yes it is,” responded Dr. Albertsen, after a moment’s hesitation, “because you can only have early, localized cancer [diagnosed] if you are screened—otherwise you’d have a tumor that causes symptoms and that’s not what we’re talking about here.” (click here for “Just say no to the PSA test.”)

There are other forces driving the overuse of ADT, according to James Talcott, MD, director of the Center for Outcomes Research at Massachusetts General Hospital Cancer Center. In a telephone interview, Dr. Talcott, who was not involved in the ADT study, said, “Two drugs [used in ADT]—Lupron and Zoladex—have been aggressively promoted by their makers—Tap Pharmaceuticals and AstraZeneca.” Both companies used illegal kickbacks to encourage and reward urologists who were high prescribers of these expensive drugs, although a less expensive drug is widely available.

“Together, these two companies had to pay over a billion dollars to the federal government in fines for kickbacks to urologists [in 2001],” said Dr. Talcott. (The kickbacks included free TVs, VCRs and seminars at resorts.) “Drugs like Lupron and Zoladex—that are given by injection or infusion—are where all the money is made,” he continued, doctors can bill for them which is not the case for drugs given orally. “A great majority of men are treated by a urologist and moved on to an oncologist only after they don’t respond to Lupron or Zoladex.”

Part of the ADT overuse problem is not the physicians’ fault, stressed Dr. Talcott. “It’s also the payment mechanism. Doctors are paid to do something like give an injection, but talking to patients is a money loser.” Dr. Albertsen made a similar point, saying it’s easier to give a drug than to explain the seemingly counterintuitive option of leaving cancer untreated.

Men are bombarded with the message that early detection is best, observed Dr. Talcott, and yes many cancers are found, but “men are at least tenfold more likely to be harmed than helped by treatment of early-stage symptomless cancer.”

Maryann Napoli, Center for Medical Consumers© March 2009

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Overtreated—Why too much medicine is making us sicker and poorer

New Book:  Overtreated  by Shannon Brownlee (NY: Bloomsbury, 2007)

In a nutshell, overtreatment is unnecessary treatment. It’s treatment that has no positive impact on health or longevity, and in many cases, causes harm. It’s the coronary-artery opening procedures given yearly to more than one million Americans for whom drug therapy has been proven to be the better choice. It’s the long-term drug regimens recommended to people at low-risk for hip fracture, heart attack or stroke. It’s the PSA blood test for finding prostate cancer at its earliest stage, despite the fact that studies have yet to prove immediate treatment is better than no treatment at all. Just to name a few.

About one-third of the medicine we receive is unnecessary, according to “Overtreated” by journalist Shannon Brownlee. “We spend between one fifth and one third of our health care dollars, between $500 and $700 billion, on care that does nothing to improve our health.” Central to this excellent book is the work of John Wennberg, MD, whose pioneering research spans four decades.

Wennberg was the first to detect wide geographic variations in medical care, first within his home state of Vermont and later in the country at large. Wennberg recalls that he embarked on this research project in the late 1960s with a notion shared by many doctors of that era: The most serious problem in American health care was that many citizens were not getting enough of it. Still, it was startling to find, for example, that in Middlebury, VT, 7% of children under the age of 16 had their tonsils removed, and in Stowe, VT, 70% of children had the operation. Similar variations were shown for other procedures like hysterectomy, hernia operations and hospitalizations for heart attacks.

Extensive interviews of 4,000 people living in this most homogeneous of states ruled out the obvious explanations like patient demand and the possibility that people were sicker in some areas of Vermont. The high rates of surgery were, in fact, driven by doctors not patients. Findings like these ultimately led Wennberg to conclude, “Medicine had wrapped itself in the mantle of science, yet much of what doctors were doing was based more on hunches than good research.” Wennberg’s work drew hostile reactions from fellow physicians, and medical journals turned down publication of his findings. When they were finally published in Science magazine in 1973, they drew no attention. More medical care was still considered to be better care.

Cost Becomes an Issue

In time Medicare provided Wennberg, who had moved on to Dartmouth Medical School, with a treasure trove of patient records to learn not only about regional variations in care for everyone over age 65 but also the cost of treatment. Cost had become a major issue for Medicare by 1995 due to the huge 6000% increase in spending over the 30 years following its launch. With Dartmouth colleagues, Wennberg spent the next three years combing through the Medicare data. One example of what they found: Medicare spent an average of $8,414 for an enrollee living in Miami compared with $3,341 for an enrollee in Minneapolis.

The price of major treatments, as it turns out, played an insignificant role in explaining the differences. The cost of a hip replacement, for example, was only slightly more in Miami than in Minneapolis. Another obvious possibility—elderly people are sicker in some areas of the country than in others—also accounted for only a small difference in cost.

Findings like these began to get national media attention, but the Dartmouth researchers still had to determine whether more care means better care. In 2000 Wennberg’s colleague Elliott Fisher, MD, conducted another study that showed Medicare recipients living in high-cost regions were no healthier and no less disabled than those in regions that got less medical care. The big shocker, however, was this: More care sometimes led to more deaths.

Ultimately, Fisher showed that the people in high-spending regions were not getting more major surgery. Rather they were getting more tests, drugs and procedures that were likely to be done even when it didn’t make sense in frail elderly people with a short life expectancy. An excess of specialists was a major part of the problem. “Patients with heart attack, hip fracture or colon cancer got more care—but not better care—in hospitals where there were more specialists,” concluded Fisher.

Eventually Fisher determined that the 2-6% increase in deaths among Medicare recipients living in high-cost regions was due to the fact that they spent more time in the hospital. Patients are exposed to all the risks that include hospital-borne infections, medical errors and the complications and side effects that come with any treatment.

The results of the Wennberg and Fisher studies have been known for years and have long been available to all in the Dartmouth Atlas of Health Care (www.dartmouthatlas.org). The author of the new book “Overtreated,” Shannon Brownlee, a senior fellow at the New America Foundation, provides a public service by calling attention to this important research which is even more relevant today when the newest costliest imaging, cardiac and other high-tech procedures receive almost instant uncritical acceptance.

Brownlee brings us up to speed on the few surgical procedures and drugs that are well studied and proven to be of value…but to a much smaller proportion of current recipients. One outstanding example is the coronary-artery-opening procedure called angioplasty, which, by the way, was shown to have wide regional variations by West coast researchers building on the Dartmouth researchers’ work.

Each year two million Americans receive an angioplasty, but studies show that only 800,000 of them who are in the midst of a heart attack are likely to benefit. The majority have other cardiac-related conditions like stable angina or shortness of breath, which can be more safely and effectively treated with the same drugs that will be given after an angioplasty. In a 2006 federally funded trial, the rate of death and heart attack was lower in those treated with multiple-drug therapy alone than in those given angioplasty plus multiple-drug therapy. Angioplasty with a stent costs insurers $10-15,000.

While angioplasty is an example of doctors ignoring scientific evidence that clearly shows who should get this treatment and who should not, there is no definitive information one way or another about the vast majority of tests and treatments. The Institute of Medicine estimates that only 4% are backed up by strong scientific evidence, more than half have very weak evidence or none.

Malpractice fears cause doctors to order more tests, but to Brownlee the more powerful reason doctors and hospitals overtreat is they are paid more for doing more. She calls for an overhaul of malpractice laws because they fail to punish and weed out incompetent doctors and to compensate patients for injuries that result from medical errors.

Brownlee takes consumers to task for contributing to overtreatment by making irrational demands for drugs advertised on TV or over-the-top diagnostic tests like an MRI for a sprained ankle. She calls for more independent sources of information like the federal Agency for Healthcare Policy and Research so that consumers can be better informed. Studies show that when they are given high-quality decision aids describing the benefits, risks and unknowns about treatment options, many will make an informed decision not to be treated.

The last chapter called “Less is More” presents solutions that will go a long way toward fixing our dysfunctional system. The ideal medical care system Brownlee envisions is one that rewards doctors for using evidence to improve quality; keeps specialist care to a minimum; coordinates care in ways that will reduce errors and overtreatment—among other ideas. Pie in the sky? Brownlee says that several U.S. health care systems have already implemented these ideas—Kaiser Permanente, Veterans Health Administration (VHA), Group Health of Puget Sound and the Mayo Clinic where doctors are on salary.

The VHA is especially interesting because it managed to turn around a failed medical care delivery system in less than a decade. The VHA decentralized its health care; put doctors on salary; makes sure every veteran has a primary care doctor at a local VHA clinic; rewards hospitals that hit performance measures set by Washington; negotiates discounts for drugs; and computerizes patient records to reduce medical errors and repeat testing. In 2003 The New England Journal of Medicine published a study that compared veterans’ health facilities with traditional Medicare. The quality of the care delivered at VHA health facilities proved to be significantly better on nearly all 11 performance measures.

Yet-another kudo for the VHA came from the independent National Committee for Quality Assurance which ranks health-care plans according to 17 performance measures, such as prescribing beta blockers for patients after a heart attack. By every measure, the VHA system outperformed the highest rated non-VHA hospitals, including those widely perceived to be the best in the country.

If the VHA can do it….

Maryann Napoli, Center for Medical Consumers©March 2008

Screening for Prostate Cancer: The More They Test, The More They Find

It’s a controversy that has been roiling among research physicians for two decades: Does the prostate-specific antigen, or PSA, blood test for prostate cancer cause more harm than good? Does the early detection of prostate cancer—that is, before symptoms appear—actually save lives? These questions still haven’t been answered, though many physicians automatically test their middle-aged and elderly male patients as if they have.

A new study conducted in Europe was initiated to see whether PSA screening symptom-free men every two years has any advantage over screening at four-year intervals. The short answer is no, but this study, published in the September 5 issue of the Journal of the National Cancer Institute, suggests that the PSA test is more likely to find non-life threatening cancers without reducing the number of advanced and potentially lethal cancers.

Monique J. Roobol, PhD, and colleagues at medical centers in Holland and Sweden based their findings on data from a large trial called the European Randomized Study of Screening for Prostate Cancer. Initiated in 1993, this trial will answer the question of whether early detection of prostate cancer reduces mortality from this disease.

The reason that this trial and its American equivalent, the Prostate, Lung, Colorectal and Ovarian Cancer trial ongoing since 1992, will take so long to provide answers is the fact that most prostate cancers found on the basis of PSA screening are either non-progressive or so slow-growing that they will never become life threatening or symptomatic. A minority of the prostate cancers diagnosed during the course of this trial will be the deadly aggressive version, and it is unclear whether early detection and prompt treatment of these fast-growing cancers will result in prolonged lives. About 17% of U.S. men contract prostate cancer and 3% of them will die of the disease.

Context Needed

Any discussion of the new study about screening intervals requires some background information on prostate cancer itself. Pathologists have long known that many of the cancers that show up in the prostate will never become lethal had they remained undetected for a lifetime. Autopsy studies of men who died in accidents show that the older they are, the more likely they will have cancer in the prostate.

That’s why the measure of a screening test’s value is not how many cancers it can find; instead it is a reduction in prostate cancer deaths. But that’s not all. Harm must also be taken into account. The detection of prostate cancers that would never progress or become lethal clearly results in a high rate of biopsies and unnecessary treatment. The latter—irradiation or surgical removal of the prostate—is associated with an increased risk of urinary incontinence, bowel dysfunction and impotence.

The diagnosis of new cases of prostate cancer increased substantially in all countries after PSA screening was introduced. In the U.S., for example, PSA screening began in the late 1980s. But contrary to expectations, the prostate cancer death rate has decreased only modestly. And it is not known whether the drop in prostate cancer mortality is due to early detection or improvements in treatment, or both. Such uncertainties can be resolved by a long-term clinical trial that randomly assigns men to be screened (with a PSA test and a digital rectal examination) or not. This describes the European and the American ongoing trials.

“Interval Cancers” Studied

The new study by Roobol and colleagues takes on yet-another unanswered question about prostate cancer screening: What is the appropriate interval for screening? In the U.S. trial, men are usually screened annually.

Not so in Europe. Some medical centers participating in the European trial screen participants every four years, and others screen every two years. This difference in intervals provided the opportunity for Roobol and colleagues to see whether one has any advantage over the other. Of particular interest was the number of prostate cancers detected in men between screening tests. These are what researchers call “interval cancers.” And they are worrisome because they are likely to be the potentially fatal, advanced cancers. A reduction in their detection would be a good sign that screening might eventually reduce the number of prostate cancer deaths.

Roobol and colleagues found that, after 10 years, more cancers were diagnosed in the men (12%) screened at the shorter (two-year) intervals than in the men (8%) screened at longer (four-year) intervals. Contrary to expectations, the number of potentially life-threatening prostate cancers was the same in both groups. The downside of too frequent screening is overdiagnosis, i.e., the increased detection of cancers that do not progress, resulting in more unnecessary biopsies and treatments.

Asked by e-mail for the bottom line message from her study, Dr. Roobol wrote, “Screening should not be done at fixed intervals but through a more personal approach. Men with very low PSA levels (<1.0 ng/ml) can, depending on their age, be screened at much longer intervals. Screening every year for me looks [like] too much for the majority of men in the age group 55 or higher.”

E. David Crawford, MD, University of Colorado Health Sciences Center, author of the editorial that accompanied this study, had this observation: “Although many of us believe that early detection is saving lives, definitive evidence is lacking.”

This uncertainty is reflected in the treatment options listed for all stages of prostate cancer on the National Cancer Institute Web site (www.cancer.gov). Whether prostate cancer is diagnosed at stage I (early) or stage IV (advanced)—no treatment is as reasonable a choice as having the prostate surgically removed or irradiated.

That raises the obvious question: Why test symptomless men when—once cancer is found—no treatment is a valid option? We still don’t know whether the man whose cancer was detected after symptoms appeared is any worse off than the symptom-less man whose cancer was detected with a screening PSA test.

More Needle Biopsies, More Prostate Cancers Detected

“Despite the considerable attention given to the prostate-specific antigen (PSA) as a screening test for prostate cancer, it is needle biopsy—and the PSA test result—that actually establishes the diagnosis of prostate cancer.”

With that as background, H. Gilbert Welch and colleagues at Dartmouth and other Medical Centers studied Medicare claims to determine the proportion of men, aged 65 years and older, who have prostate cancer after a needle biopsy (removal of prostatic tissue by inserting a thin needle through the rectum and into several sections of the prostate). Their study was published in the September 19 issue of the Journal of the National Cancer Institute

The researchers found: Over 10,000 needle biopsies were performed in 1993 through 2001 in 8,273 men, age 65 and older. The overall proportion of needle biopsies found to contain cancer was 32%, and it increased with age—35% for men in their late 70s and 41% for men over age 80.

The risk of finding prostate cancer increased with repeat biopsies in those initially found to be cancer-free, with 50% of the men diagnosed with prostate cancer after two biopsies, 62% after three biopsies and 68% after four biopsies.

The odds of finding cancer go up not only with the age of the man undergoing a needle biopsy but also the number of tissue samples taken. Over the years, the needle biopsy has become more and more aggressive. Initially, needle biopsies consisted of jabs for prostate tissue in six different sites. Now many urologists advocate 12 or more and some even advocate “saturation biopsy,” which involves 32 to 38 jabs, say Welch and colleagues, “the more biopsies taken, the more cancer is found.” The incidence of biopsy-induced infection was not recorded in this study.

Maryann Napoli, Center for Medical Consumers ©
November 2007

Early Promoters Of PSA Screening For Prostate Cancer Do A Turnabout

At first, it appeared to be heresy. A paper published last October in the Journal of Urology indicates that the PSA screening test for prostate cancer has lead to widespread cancer diagnoses in men who did not need to be treated. The paper entitled, “The prostate specific antigen [PSA] era in the U.S. is over for prostate cancer: what happened in the last 20 years?” received surprisingly little publicity. What made it so remarkable was the fact that the lead author, Thomas A Stamey, MD., and colleagues at Stanford University are credited with early promotion of PSA screening in a paper published in 1987. Now, their recent data present a powerful argument against this use in symptomless men.

The paper describes a study that shows the presence of cancer in the prostate increases with age. Autopsies conducted on 525 men, equally divided between white and black men, killed accidentally on the streets of Detroit , showed that 8% of those in their 20s had prostate cancer. There was a linear increase in prostate cancer with each increasing decade of life. About 80% of the men (of both races) who were in their 70s had invasive prostate cancer.

The fact that most prostate cancers will remain dormant is demonstrated aptly by another statistic in this paper: “[Prostate cancer] has an extraordinarily small death rate of 226 per 100,000 men older than 65 years,” wrote Stamey and colleagues. Deaths from prostate cancer are rarer yet in men under age 65, according to the National Cancer Institute. Yet despite these statistics that make a case for not screening symptomless men for prostate cancer, the PSA blood test began to go into widespread use in the late 1980s. There is still no test that can accurately distinguish slow-growing or latent prostate cancer from the type that is moderately rapid and fatal.

Over the course of two decades, Dr. Stamey and colleagues assessed 1,317 consecutive prostates that had been removed surgically between 1983 and 2003—what they called the “PSA era.” The idea was to see how well the PSA test given before surgery accurately reflected the size of the largest cancers. Here’s what they found: “In the first ten years after PSA screening was introduced, there was a reasonably good, although not great, correlation between serum PSA and prostate cancer volume.”

But, as the years went by, things changed completely. When the researchers assessed the prostates removed most recently, that is, between 1998 and 2003, they found that the PSA tests were detecting benign enlargement of the prostate, rather than cancer. Benign prostatic hyperplasia, or enlarged prostate, is a common condition in men over age 60.

Dr. Stamey and colleagues explained their findings in this way: American men between 50 and 80 years have been screened so intensely over the last 20 years that the most significant of the prostate cancers had already been detected. However, they glossed over the substantial harm done to men in the PSA era in terms of unnecessary prostatectomies and unnecessary radiation therapy. The issue was alluded to in only one sentence, using one word— overtreatment.

In a telephone interview, Dr. Stamey said he had no hope that the huge industry that has now built around PSA screening will disappear with his findings. So he stressed the importance of informed consent where it concerns the use of the PSA test in symptomless men. “It is immoral for surgeons not to tell patients that we [men] all get prostate cancer as we age,” said Dr. Stamey, after describing himself as a 76-year-old surgeon who hasn’t had a screening PSA test in several years.

“Patients should be told that there’s a high chance of having prostate cancer that rises with age, but a very low chance of dying of it. Do we really want to screen 100,000 men to save 226 from dying of prostate cancer? In fact, it’s about the same chance of my not driving home safely tonight.” What’s more, he continued, 20 years ago, the prostate was biopsied in only six places, now it’s 36.

What about the PSA test’s possible role in the slight dip in the U.S. prostate cancer death rate? Dr. Stamey gave no credit to PSA screening.

“The death rates from several other common cancers have fallen, too, but we have no idea why.”

Maryann Napoli, Center for Medical Consumers ©
February 2005

Survey Of Patient Education Materials About Prostate Cancer Treatment

One-Sided Information Common

Our office often receives calls asking for a source of balanced information about the treatment options for early prostate cancer. It has always been a stumper. Our usual recommendation is the National Cancer Institute’s treatment summaries (www.cancer.gov), but this is a disappointing source of information where it concerns prostate cancer. Unlike other cancers, this one might be just as well left undetected and untreated (more on that later), and it is hard to find anything that gives a balanced view of all options, including no treatment. In fact, we have yet to find one.

That’s why we were interested in a new survey of “Patient Education Materials about the Treatment of Early Prostate Cancer,” published last month in Annals of Internal Medicine. 546 consumer pamphlets and Web sites were surveyed and given scores based on these two crucial questions: Are all the options presented? Are the potential harms as well as potential benefits presented? Professional organizations, medical centers, and drug companies were among the publishers of the educational materials in this survey.

What makes early-stage prostate cancer such a good test of an information source’s honesty is the fact that no head-to-head comparison study of all three treatment options has ever been conducted, though radical prostatectomy has long been the common treatment. For what other cancer would a prospective patient face the choice of having an organ removed, irradiated, or left alone unless symptoms develop (watchful waiting)—all of which are equal in terms of survival?

So when this patient education materials survey was published last month, we were ready to champion the top choices in this newsletter and add a link within our Web site to those with the high scores. The first stop was the Web site of the medical division of the University of Toronto (www.library.utoronto.ca/medicine/prostate).

After multiple failed attempts to get through and no response from the site’s Web master, it was on to the next high scorer, the Web site of Memorial Sloan-Kettering Cancer Center, which describes itself on the local public radio station as providing, “The best cancer care anywhere.”

This Web site’s information amounts to a sales pitch for certain radiation and surgical techniques pioneered by doctors at Memorial Sloan-Kettering Cancer Center. Don’t expect a full explanation for why watchful waiting might be worth considering. This option merits only five sentences. The American Cancer Society wasn’t any more forthcoming on watchful waiting, providing exactly the same minimal amount of space.

How did these Web sites score so high? That question merited a return to the statements written by Angela Fagerlin, PhD, of the University of Michigan, and colleagues after completing their survey:

All sites reviewed were accurate, but some erred by omission, most typically de-emphasizing side effects of therapy. Several sites presented so little of the key content that they generated somewhat misleading impressions.

And this about the printed materials:

No print education materials we evaluated had clinically significant misstatements, although some references were out of date because of the publication date. We found only one case of clinical significant imbalance in the treatment descriptions. However, a general bias was toward active treatment that minimized the role of watchful waiting. In addition, the likelihood and impact of side effects were minimized [emphasis ours].

What is really needed here is not just a balanced view of treatments, but an honest view of prostate cancer. Men die of prostate cancer. A small percentage of all prostate cancers are aggressive, and rapidly fatal no matter how early they are detected and treated. The majority, however, are so slow growing that they will never become life threatening or produce symptoms. In between, there may be a small proportion of men with a type of prostate cancer that could benefit from early detection and immediate treatment. An ongoing clinical trial is pursuing the question of whether early detection of prostate cancer is lifesaving. Though men will be told their PSA and Gleason scores, no test can determine accurately which prostate cancers will become aggressive and which will remain dormant.

As this survey shows, treatment-related harms are usually left out of the information given to patients. Since the choice of watchful waiting is counterintuitive to most people, it deserves a clear and lengthy explanation. After all, hasn’t the early-detection-saves-lives message been drummed into the public’s consciousness for years?

There is a reasonable amount of preliminary research to suggest that men should give serious thought to avoiding a PSA test for prostate cancer because it is unclear whether early treatment is lifesaving. For example, a Swedish study, which had randomly assigned men to watchful waiting or radical prostate surgery, showed that the men who underwent surgery did not live longer than those who did not. After six years, there were 4% fewer prostate cancer deaths among the surgically treated men. That benefit, however, was canceled by the fact that their quality of life was worse (incontinence and impotence are treatment complications) and their 4% higher rate of deaths from other causes.

Several studies monitored untreated men with favorable results, for example, one followed Swedish men who were not treated unless symptoms developed. At 15 years, those whose cancers appeared to be confined to the prostate at diagnosis had a prostate cancer death rate of 11%. In the U.S., men treated with a radical prostatectomy for early-stage disease have a similar mortality rate. Don’t expect to hear about these studies from your average urologic surgeon. And there is no financial incentive for a medical center’s Web site to provide a balanced description of watchful waiting.

What you can do:

• Send for the free pamphlet that got the best score in the print material category by calling the National Cancer Institute (NCI) hotline, 1(800) 4-CANCER. Ask for “Understanding Treatment Choices for Prostate Cancer.” The same pamphlet can be read at the NCI Web site (www.cancer.gov/prostate). It includes a survey of prostate cancer patients’ experiences with treatment-related complications, such as incontinence and impotence.
• Talk over the options with a knowledgeable primary care physician. When getting a second opinion about treatment, recommendations will correspond to the bias of the specialist. Not surprisingly, urologic surgeons advise surgery and radiation oncologists recommend radiation therapy. As with the information sources in this survey, a test of a primary care doctor’s knowledge would be his or her opinion of watchful waiting.
• Do not have a PSA screening blood test for prostate cancer without informing yourself beforehand. Read the new book entitled Should I be Tested for Cancer? Maybe not and here’s why (Berkeley: University of California Press) by H. Gilbert Welch, MD.

Maryann Napoli
June 2004

PSA Screening Test for Prostate Cancer

An Interview with Otis Brawley, MD

By Maryann Napoli

The prostate-specific antigen (PSA) screening test for early prostate cancer has been surrounded by controversy ever since it was introduced over 15 years ago. The test can indicate the presence of cancer, but many men have a form of prostate cancer that will remain dormant or is so slow-growing that it will never cause symptoms. Neither this test, nor any other can distinguish which prostate cancer will become lethal. Furthermore, there is no proof that the use of the PSA blood test to screen symptom-free men will spare anyone a prostate cancer death, yet it is associated with a considerable amount of unnecessary treatment with aftereffects that can be both severe and permanent. All of the treatments for early prostate cancer carry the risk of impotence and incontinence. In short, cancer researchers do not know whether PSA screening saves more lives than it ruins. (Update: In 2009, two important clinical trials published contradictory results click here.)

Otis W. Brawley, MD, is the brains behind the ongoing National Cancer Institute Prostate Cancer Prevention Trial, which is designed to answer questions about the effectiveness of screening and the causes of prostate cancer. After leaving the National Cancer Institute, Dr. Brawley became the Director of the Georgia Cancer Center and Professor of Medicine, Oncology, and Epidemiology at Emory University School of Medicine. He is interviewed about the ever-increasing use of PSA screening in the face of so much uncertainty about its value.

Napoli: Does the popularity of PSA screening concern you?

Dr. Brawley: First of all, I’m not against prostate cancer screening. I’m against telling people that it is well established; and that it works; and that it saves lives when the evidence that supports those statements simply does not exist. I’m a tremendous supporter of the real American Cancer Society (ACS) recommendation, which is: Within the physician-patient relationship, men should be offered PSA screening and should be informed of the potential risks, as well as the potential benefits and be allowed to make a choice.

Napoli: Do you think fully informing men about PSA screening happens very often?

Dr. Brawley: I think it rarely happens. Many doctors are uninformed, and that’s a big problem. My great concern is people being misled. I routinely follow the prostate cancer screening recommendations of 18 organizations in the U.S., Canada, and Western Europe. The two most pro-screening recommendations are those of the ACS and the American Urologic Association. Both of whom say it should be offered to men; men should be informed of the potential risks and the potential benefits; and they be allowed to make a choice. The ACS does not recommend that men of normal risk be offered mass screening. There’s a distinction between what is done within a doctor/patient relationship at a doctor’s office and mass screening.

Napoli: What is the difference?

Dr. Brawley: Mass screening takes place at a booth at a mall where screening is offered to anyone who comes by and wants screening. In the last few years, there has been screening on the floor of the Republican National Convention, health fairs at the mall, [TV] channel this or channel that will have a health fair with prostate cancer screening. Yet there is no organization that endorses mass screening because of the concern that you can’t have informed consent.

Napoli: If policy makers aren’t promoting the test, who is?

Dr. Brawley: The British Medical Journal recently published an article about how several of the leading prostate cancer survivor organizations [based in the U.S.] that do a lot of the pushing of screening are funded by the makers of the PSA screening kits. And, indeed, [these survivor organizations] do things that the Food and Drug Administration won’t let the manufacturers do—like make promises that there are only benefits from prostate cancer screening. Many of these prostate survivor organizations that I’m critical of—that take drug company money—offer mass screening.

Napoli: You were once quoted in The New York Times saying that 30-40% of men whose cancers appear to have been confined to the prostate at diagnosis will recur soon after treatment.

Dr. Brawley: Yes, this [brings up] one of the lies perpetrated about prostate cancer. If you look at the prostate cancer outcomes from a huge study conducted by the National Cancer Institute, close to 40% of men who undergo a radical prostatectomy will have a PSA relapse within two years. This means that they had disease that was outside of the prostate that was not obvious to the surgeon or the pathologist. It means that if the man lives long enough, metastatic disease will kill him.

Napoli: The public is always told that early detection is lifesaving. How true do you think that is for prostate cancer?

Dr. Brawley: If you have a group of men diagnosed as a result of PSA screening, 30-40% don’t need to know that they have prostate cancer because it’s meaningless in terms of risk to their health. And for somewhere between 30% and 40% of the men with prostate cancer, no matter what [treatment is given], the disease is not curable. And then maybe there are about 20% who actually benefit.

Napoli: And there’s no way to know which type of prostate cancer you have.

Dr. Brawley: That’s right.

Napoli: What about African American men, who as a group, are at a particularly high risk for prostate cancer? PSA testing is thought to be advisable for them at an earlier age.

Dr. Brawley: The proportion of black men in Rocky Feuer’s paper [for the Journal of the National Cancer Institute] who don’t need to know they have prostate cancer was over 40%, compared to 30% of white guys. The reason it’s higher for black men is that they have so many other competing causes of death. The other issue is this: It’s a principle of cancer screening that, unfortunately, many of the advocates of screening just don’t comprehend, and that is, the more aggressive cancers are less likely to benefit from screening. There are people out there who say we must screen black men because they have more aggressive prostate cancer. [These screening proponents] do not realize that they are saying, in effect, because prostate cancer screening is less likely to benefit black men, then we must screen black men.

Napoli: You recently published a medical journal article about informed consent and the PSA test.

Dr. Brawley: Yes, the problem I have is that people are not open and honest about all the controversies, and this extends to people being not open and honest about the treatments, once prostate cancer is diagnosed. Men tend to get railroaded toward radical prostatectomy or to external-beam radiation, or to seed implants.

Napoli: Since there’s no evidence that any one of these treatments is superior to another or superior to no treatment, for that matter, where do you suggest men go for unbiased information?

Dr. Brawley: First of all, I think we should tell men what is scientifically known and what is scientifically not known and what is believed and label them accordingly. [As for credible sources of information,] the National Cancer Institute’s PDQ treatment statements at http://www.cancer.gov are good [call 800/4-CANCER]. So is the ACS’s information. And by the way, we at Emory have figured out that if we screen 1,000 men at the North Lake Mall this coming Saturday, we could bill Medicare and insurance companies for $4.9 million in health care costs [for biopsies, tests, prostatectomies, etc]. But the real money comes later—-from the medical care the wife will get in the next three years because Emory cares about her man, and from the money we get when he comes to Emory’s emergency room when he gets chest pain because we screened him three years ago.

Napoli: You’re saying that screening creates long-term customers. So, did Emory Healthcare decide to go ahead with the free PSA screening on Saturday?

Dr. Brawley: No, we don’t screen any more at Emory, once I became head of Cancer Control. It bothered me, though, that my P.R. and money people could tell me how much money we would make off screening, but nobody could tell me if we could save one life. As a matter of fact, we could have estimated how many men we would render impotent…but we didn’t. It’s a huge ethical issue.

Surgery For Early Prostate Cancer

Surgery for Early Prostate Cancer
By Maryann Napoli

When a man is diagnosed with early prostate cancer, he faces several options but no clear answer to the most crucial of all questions: Is treatment better than no treatment at all? A new Swedish study showed that surgical removal of the prostate does, in fact, reduce a man’s odds of dying of prostate cancer, but worsens his quality of life.

Unfortunately, the finding has little relevance to most American men because prostate cancer screening has become so popular in this country that the majority are diagnosed before they have any signs or symptoms of the disease. This was not true of the majority of the Swedish men who participated in the study published last month in The New England Journal of Medicine (9/12/02).

Americans Diagnosed Earlier

The term early means that the cancer has not spread beyond the prostate gland. But there are degrees of “early.” The majority of the Swedish participants had tumors that could be felt by a digital rectal examination, and many had symptoms, such as difficulty urinating. Whereas 75% of American men with prostate cancer do not have a tumor that can be felt, nor do they have symptoms. They are diagnosed after a biopsy performed as a result of a PSA screening test. The Prostate-Specific Antigen (PSA) test identifies a protein in the blood that can indicate the presence of a cancer too small to be felt. Originally intended as a follow-up test for men who had been treated for prostate cancer, the PSA test has been promoted to symptomless men for over a decade.

The relatively small group of newly diagnosed American men who fit the profile of the 695 participants in the Swedish Study should take note: The results of this study are a wash. At six years, the men who had a prostatectomy (surgical removal of the prostate) had a lower death rate from prostate cancer, but it was canceled out by a higher death rate from other causes. If the aim is solely to reduce the odds of dying of prostate cancer within the next six years, then surgery is the way to go. Only 4.6% of the men died of prostate cancer after undergoing a radical prostatectomy; where 8.9% of the untreated men died of the disease.

If, however, the goal is to lower the odds of dying from any cause, then no treatment may be the way to go. The overall death rate in both groups was exactly the same. It is possible that the surgically treated men died of treatment-related causes, such as an infection. In that case, their deaths would not be counted as prostate cancer deaths. All the men were under the age of 75, with an average age of 64 years.

By counting the overall death rate-that is, the deaths from all causes-the authors of this study are following an important new trend in research. They are stepping back and looking at the big picture, as opposed to looking solely at the question of whether X medical treatment lowers the death rate from Y disease. Too often, the treatment itself will cause deaths, but they go uncounted by most researchers. Here is the conclusion of the Swedish study: “…there was no significant difference between surgery or watchful waiting in terms of overall survival,” wrote Lars Holmberg, MD, and colleagues at the Scandinavian Prostatic Cancer Group Study.

The Swedish research team noted that there were 37 deaths from other causes in the surgically treated group and 31 in the untreated group. “This difference could be due to chance or to long-term but hitherto unknown adverse effects of prostatectomy.”

While it is unusual for researchers to address the overall death rate in the conclusion of their study, the finding itself is not. There are already several examples of medical interventions that reduced the death rate from cancer but failed to lower the overall death rate. For example, several randomized controlled trials showed that screening tests for colon cancer reduce the rate of deaths from this disease, but inexplicably increase the death rate from heart disease. More recently, a review of all the best mammography clinical trials came to a similar conclusion about the overall death rate.

Symptoms Worsen After Surgery

Now for the question of quality of life. It’s certainly possible that a prostatectomy could improve a man’s life without prolonging it. Consequently, the Swedish research team sent questionnaires to the 326 men who had symptoms at the start of the study to see how they fared four years later. The percentage of men suffering the following symptoms was consistently higher among the surgically treated, as compared to the untreated: impotence (80% vs 45%), “distress from compromised sexuality” (55% vs 40%), urinary leakage (49% vs 21%), “distress from all urinary symptoms” (27% vs 18%).

The clinical trial with the most relevance to American men is currently in progress, and results will not be available until 2008. It is sponsored by the Department of Veterans Affairs, the National Cancer Institute and the U.S. Agency for Health Research and Quality. The 731 participants had cancer that was confined to the prostate, and most were diagnosed initially with a PSA test. The men were randomly assigned to have their prostates removed or to remain untreated. The lead researcher, Timothy J. Wilt of the Minneapolis VA Medical Center, recently told The New York Times that five years into the study, no survival advantage has been shown for either group.

Although there are other treatment options for men with localized prostate cancer, such as radiation therapy and radiation seed implants, no head-to-head comparison study has ever been done.

(October 2002)