USPSTF Says “No” to PSA Screening

[gdpawel]

[Richard M. Hoffman, MD, MPH, is a general internist, Professor of Medicine at the University of New Mexico School of Medicine and a staff physician at the Albuquerque VA Medical Center. He also serves as Interim Director for Cancer Prevention at the University of New Mexico Cancer Center. His areas of research interest are prostate and colorectal cancer screening and prostate cancer treatment outcomes, with expertise in clinical epidemiology, health services research, and meta-analysis. He is a medical editor for prostate cancer topics for the Foundation for Informed Medical Decision Making and works with the Foundation to develop shared decision making tools for prostate cancer screening and treatment of localized prostate cancer.]

Once again, the United States Preventive Services Task Force seems headed for a storm of controversy. The Task Force concluded that screening should be discouraged because it has no net benefit or the harms outweigh the benefits.

Not even two years ago, the Task Force's recommendation against routinely performing mammography in average-risk women before age 50 outraged professional organizations, advocacy groups, celebrities, politicians, and many other vocal critics. Unfortunately, the somewhat awkward message was distorted to imply that these women should never undergo mammography. In fact, the Task Force was highlighting that mammography for these women involved important trade-offs between potential benefits and harms--and that women needed to make informed, personalized decisions. This is an appropriate message.

However, the new recommendation on prostate cancer seems troubling. In 2008, the Task Force gave prostate cancer screening an "I" rating because the available evidence was considered insufficient to recommend for or against screening--largely because there were no valid data from randomized controlled trials of screening. The Task Force suggested that men be informed about the risks and benefits of screening, though strongly advised against screening men age 75 and older.

In 2009, long-awaited results from the major randomized controlled trials were published. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found that screening reduced prostate cancer mortality by 20%. In contrast, the American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found no benefit with screening. However, evaluating PSA in America was challenging because screening was so pervasive that investigators had difficulty enrolling men who had never been screened--or preventing screening in the control group. The validity of the negative PLCO results is uncertain. The ERSPC study was more credible, but showed only a small absolute survival benefit. This benefit must be balanced against the harms of overdiagnosis--finding cancers that would never cause clinical problems during a man's lifetime--and the resulting overtreatment, which can lead to urinary, bowel, and sexual dysfunction.

Unfortunately, we cannot confidently identify the "overdiagnosed" cancers found with screening, so most men will undergo surgery or radiation therapy. A new strategy of active surveillance might mitigate the harms of overdiagnosis. With this option, men are closely monitored with PSA tests, digital rectal examinations, and biopsies--and will be offered surgery or radiation only if the cancer shows signs of being aggressive.

Ideally, men should be making an informed decision that best reflects their values for the potential downstream consequences of screening. This is indeed the conclusion (based on similar clinical data) that the Task Force reached regarding mammography for women before age 50. The Task Force classified this as a grade "C" recommendation--which is what I expected for prostate cancer screening.

USPSTF's grading system [url]http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm

Source: HealthNewsReview.org

The National Cancer Institute tracks US cancer epidemiology through its SEER (Surveillance, Epidemiology, and End Results) tumor registries. SEER reports that men diagnosed with localized prostate cancer (that hasn't spread beyond the prostate) have a 0% chance of dying from this cancer over the next 5 years, regardless of whether the man receives treatment. This means that they need to follow men for at least 10 to 15 years following diagnosis to determine whether treatment improves cancer survival.

[gdpawel]

By: Len Lichtenfeld, M.D., Deputy Chief Medical Officer, American Cancer Society

A report from the venerable United States Preventive Services Task Force made it to the media yesterday–a bit ahead of schedule–and it not only says we aren’t certain whether a man should get a PSA test to find prostate cancer early, it came flat out and proposed, effectively, “Don’t do it!”

That proposed recommendation that is going to create a good deal of discussion, I would think.

Whether PSA testing to find prostate cancer early really saves lives is not certain. The test has been around for over two decades, but it wasn’t until recently that there were any scientific studies that could provide evidence whether or not the test actually worked. And those two studies produced conflicting results, or so it seemed.

One study done in several European countries found that PSA screening reduced deaths from prostate cancer by about 20%. Another study done in the United States concluded that PSA screening did no such thing. In fact, in the US study, the deaths from prostate cancer were greater during the period of the study in men who were screened vs. those who were not, but that difference was not found to be statistically significant.

Basically, what has happened is that the Task Force reviewed all of the evidence as to whether or not PSA screening decreased death rates from prostate cancer, and whether or not the harms from early diagnosis and treatment outweighed the benefits.

In reviewing the available studies, they found studies that tried to answer the question, but didn’t find any that were really well done. So they had to rely on a lesser level of evidence, and among that evidence were the two studies noted above.

In the European study, they pointed out that for ALL of the men included in the study, ages 50-74, there was no reduction in deaths in the group with PSA testing. They also pointed out that the European study was in fact a “compilation” of trials in several centers in several countries, and that the frequency of PSA testing differed considerably from center to center (every 2-7 years, not every year as is commonly done in the United States).

The USPSTF researchers also pointed out that the group where the reduced death rates were found was in fact a “select” group of men ages 55-69. Furthermore, not all men in that study were treated equally: men who were in the “PSA testing arm” were treated in academic centers, where they would have arguably received better care, compared to the untested control group who were treated in community hospitals.

Another wrinkle was highlighted by the researchers who pointed out that one of the Swedish centers that participated in the trial had exceptionally good results (in fact the only center in the study that had such great results). Take that center out of the analysis, and voila! the benefits of screening in the European study miraculously vanishes.

Then there was the United States study, were many of the men in the “untested” control arm had PSA tests anyway, thus making the results of “no benefit” less than clear cut.

I could go on, but I think you can begin to understand the dilemmas all of us have faced in trying to figure out whether or not PSA testing really works. And let’s not ignore the question of what happens to men after they receive treatment for their prostate cancer, problems that are not insignificant such as incontinence of urine, difficulty with bowel movements, impotence and more. These are not minor issues.

So here is a test that has strong advocates, not the least of whom are the truly well-meaning men and their loved ones, friends and colleagues who truly believe that PSA testing saved their lives. And not a few of those men are in positions of influence, including a number of Congressmen and Senators, senior executives, celebrities, you name it. They were told that PSA testing saved their lives and I would expect they would take that advice to heart. Hear it often enough, and you believe it.

But just saying something often enough, loud enough and clear enough does not make it so. Just ask the women who took all those hormones for all those years, and all those doctors who thought they were doing the right thing for their patients by prescribing those medications. They too thought hormones were good for their health, until the evidence proved it wasn’t so. (Hormone therapy remains a useful treatment, but only with a clear understanding of the risks and benefits of those treatments.)

So, now the horns of the dilemma. The Task Force is now on record as proposing a recommendation that men NOT get PSA testing. They conclude there is no real proof of benefit, and real proof of harms. Too many men go through too many treatments with too many long -lasting complications without a clear expectation that it will save their lives.

That’s pretty radical, and is certain to raise a firestorm of criticism among those who believe that PSA testing saves lives.

The American Cancer Society went through the same evidence a couple of years ago and had the same discussions. We elected to say to men that we did not know whether or not PSA testing saved lives, but thought the best approach was for men and their health professionals to have a clear discussion, outlining the benefits and risks before embarking on a program of PSA testing. And that remains our recommendation today.

But I will say that even then, the evidence of benefit from PSA screening was certainly not overwhelming, if it existed at all. We knew then about the issues with the United States trial; there were whispers about some problems with the European study that are now more clearly discussed in the Task Force report. But the bottom line remains for both organizations that the evidence is not firm that the test makes a real difference.

After all this, you know what really gets me upset?

We have invested over 20 years of belief that PSA testing works. Catch it early, treat it early, and get it out. Save a life. That’s the mantra many of us–including me, as a practicing physician–believed. And here we are all of these years later, and we don’t know for sure. That is not an acceptable situation. Plain and simple, we have not done our homework to prove our point. And the chickens are coming home to roost.

Unfortunately, those “chickens” are men like me who dutifully get our blood tested every year. We have been poked and probed, we have been operated on by doctors and robots, we have been radiated with fancy machines, we have spent literally billions of dollars. And what do we have? A mess of false hope?

Back in the early part of this decade, researchers came to the conclusion that although there were some benefits to hormone therapies for post-menopausal women, there were more harms that outweighed their routine use. Almost a decade later, there has been a significant decline in hormone usage, we are more aware of the risks, we counsel our patients carefully about the use of these medicines, and we recommend the lowest dose for the shortest period of time.

Now we are about to face similar issues with prostate cancer screening. We will argue, we will refute the other persons science, yet I suspect we will come to an understanding that just because experts, doctors and grateful patients and their families say it often enough and loud enough does not make it so.

As someone reminded me recently, anecdote is not a form of evidence. And for PSA screening, unfortunately, according to the Preventive Services Task Force, the evidence just isn’t there.

It’s always hard to learn that the emperor in fact has no clothes. The sad reality, however, is that this debate is not about a fairly tale. It’s real life, my friends. And people have been hurt, and doctors have been deceived. At least, that’s what the Task Force is saying.

Maybe it’s time to listen to evidence instead of hope. Sometimes that’s hard to do.

[gdpawel]

Zosia Chustecka
Medscape Medical News

October 7, 2011 — Routine screening for prostate cancer using the prostate-specific antigen (PSA) test will no longer be recommended in the United States, where it is currently used more than in any other country in the world, according to a draft recommendation. The draft recommendation against routine screening with the PSA test comes from the US Preventive Services Task Force (USPSTF).

The USPSTF already recommends against routine PSA screening in men older than 75 years. In the new draft recommendation, it extends this to all men. It now recommends against routine screening in men younger than 75 years, giving this a "D" rating, which means there is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits.

Based on Reviews of Trials

The recommended change is based on a review of 5 randomized trials of screening and 3 trials and 23 cohort studies of treatments. Included in the review were the 2 largest trials of PSA screening, which reported conflicting results, the USPSTF notes. The European study found a reduction in mortality after 9 years of screening, but the American trial, which had high crossover and contamination rates, found no reduction in mortality after 10 years of screening.

The review also noted that treatment for prostate cancer, such as prostatectomy and radiation, is associated with risks for problems such as erectile dysfunction, urinary incontinence, and bowel dysfunction.

The USPTSF concluded that after about 10 years, PSA-based screening results in small or no reduction in prostate-cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.

Delay in Announcement

This recommendation has been a long time coming, according to reports in the October 7 issue of the Cancer Letter and in the New York Times magazine. They assert that the timing of the release of this recommendation was influenced by political considerations. According to these reports, the task force first voted to recommend against routine PSA screening back in November 2009, but this caused a violent political firestorm, and subsequent follow-up meetings were cancelled. The final vote was taken in March. After this, a paper summarizing the recommendation was submitted to the Annals of Internal Medicine, where is it expected to appear.

PSA Test is Not Specific

The main problems with the PSA test are that it is not specific for prostate cancer and it cannot differentiate between aggressive and indolent forms of the disease.

"It cannot distinguish cancer that will never make a difference in a man's lifetime from cancers that will make a difference," so might prompt men to undergo aggressive treatment unnecessarily, Virginia Moyer, MD, MPH, chair of the USPTSF panel that made the recommendation, stated in an interview with Bloomberg News. "So you go from being a guy who feels fine and who is potentially one of the majority who would never have known they had this disease, to being a guy who wears adult diapers," she said. Dr. Moyer is a professor of pediatrics at Baylor College of Medicine in Houston, Texas.

The PSA test is "hardly more effective than a coin toss," said Richard Ablin, PhD, research professor of pathology at the University of Arizona College of Medicine in Tucson. Dr. Ablin discovered PSA in 1970. Using this test to screen for prostate cancer in the general population has been a "hugely expensive public health disaster," he wrote in an opinion piece in the New York Times.

"Drug companies continue peddling the tests, and advocacy groups push prostate cancer awareness by encouraging men to get screened," he wrote. "The medical community must confront reality and stop the inappropriate use of PSA screening," he stated. "Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatment."

Although PSA testing is recognized as being imperfect, it is the only test for prostate cancer that is widely available, and it does provide information that can be useful, proponents point out. One of the professional bodies that has long supported the use of the test, the AUA, emphasizes that it should not be used on its own, but needs to be combined with other information (such as family history).

The AUA issued a statement in reaction to the new USPSTF recommendations: "We are concerned that the Task Force's recommendation will ultimately do more harm than good to the many men at risk for prostate cancer, both here in the United States and around the world."

"The AUA's current clinical recommendations support use of the PSA test, and it is our feeling that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pretreatment staging or risk assessment, and post-treatment monitoring of prostate cancer patients," according to the statement.

"Not all prostate cancers require active treatment and not all prostate cancers are life-threatening," the statement points out, and the decision of whether to proceed to active treatment or whether surveillance is an option needs to be discussed in detail with the patient.

The Agency for Healthcare Research and Quality supported this study. Author disclosure information is available on the Annals of Internal Medicine Web site.

Ann Intern Med. Published online October 7, 2011.

Zosia Chustecka is news editor for Medscape Hematology-Oncology and prior news editor of jointandbone.org, a Web site acquired by WebMD. A veteran medical journalist based in London, UK, she has won a prize from the British Medical Journalists Association and is a pharmacology graduate. She has written for a wide variety of publications aimed at the medical and related health professions. She can be contacted at [email]ZChustecka@webmd.net

Note: According to Dr. Matt Cooperberg, assistant professor at UCSF, active surveillance for prostate cancer means that based on the information available, the likelihood of cancer progressing in the short-term, while not zero, appears to be very low. Active surveillance does not mean the cancer will never need to be treated, but rather that it does not need treatment now. The "window of opportunity" for curing low risk prostate cancer is measurable in years in most cases, if not decades. In the meantime, men can avoid the risks and costs of surgery, radiation therapy and other interventions.

[gdpawel]

[Merrill Goozner occasionally writes for the Journal of the National Cancer Insitute.]

Over a ten-year period, about 15 to 20 percent of men receiving routine PSA tests will be sent for biopsies because of elevated PSA values;

Yet elevated PSA values are not specific to cancer; 80 percent of the men sent for biopsies will not have cancer;

About one in 24 men sent for biopsies will wind up being hospitalized with complications from the procedure within a month;

About 90 percent of all prostate tumors successfully identified by the biopsies will not be metastatic, but will be localized, which makes them prime candidates for “watchful waiting,” not aggressive treatment;

Yet 75 percent of those identified with cancer will wind up receiving either radiation, or surgery, or both;

Five out of every 1,000 men who have prostate cancer surgically removed will die within 30 days of complications of the operation;

Ten to 70 of 1,000 men who receive surgery will have serious complications, including heart attacks and strokes;

Anywhere from 200 to 300 of those 1,000 men who receive aggressive treatment for prostate cancer (radiation or surgery) will become either incontinent or impotent or both;

In the European trial, which showed benefit from PSA testing while the U.S. trial did not, there needed to be 48 men screened every year for ten years to save one person from dying from prostate cancer.

To sum up, treat 1,000 men identified with prostate cancer and 200 to 300 will become impotent or incontinent; among those who get surgery, five will die from operation complications, and 10 to 70 will have heart attacks, strokes or other serious adverse events. That compares to about 20 lives not lost to prostate cancer for every 1,000 men treated, if I’m doing the math right.

For those of us who follow medicine closely, we understand science drives these studies, just as science drives the decision-making process at USPSTF. But its parent agency, AHRQ, does itself no favors when it explains these scientific decisions late on a Friday afternoon, a week after the announcement, and gives the press and public no chance to ask questions.

Merrill Goozner

[gdpawel]

MDS (myelodysplastic syndrome) is characterized by an excess of blasts in the Bone Marrow 5-20%. The ONLY difference between MDS and leukemia is that the term "leukemia" is only used when the number of blasts reaches 20% or more.

Radiation can be a causal factor in this disease, as well as age. My brother-in-law (70 at the time) developed MDS after being treated for local prostate cancer with radiation pellets (brachytherapy). Treatment-related MDS or secondary MDS is often more severe and difficult to treat than de novo MDS (unknown changes to the bone marrow).

You don’t have to receive chemotherapy and/or radiation to get this disease. Simple aging is enough. When we are exposed to enough radiation through natural means to disrupt our DNA or, perhaps our DNA just falls apart on its own. Most patients with myelodysplasia who have not received anti-cancer treatment are in their 70’s and 80’s.

There are different varieties of this disease and doctors can distinguish them by looking at the appearance of the bone marrow cells as well as testing their DNA for mutations. People with the most peculiar cells have the shortest life span after diagnosis, about a year or two, although a few can last as long as ten years. Others with good-looking cells can live anywhere from five to fifteen years or even longer. The same holds for genetic changes. Certain ones are associated with very short survivals and others, with much longer life spans.

I guess my brother-in-law had the most peculiar cells, he died a short time afterwards.

When people die from this, it is usually because they can’t make enough infection fighting cells and get overwhelming infections such as pneumonia. Or, they develop acute leukemia. This type of leukemia that develops in people with myelodysplasia is virtually untreatable – different from other kinds of leukemia. Also, remember that the patients are generally elderly so that they can’t handle aggressive treatment or the stress of not enough blood cells.

Is it cancer? Most cancer specialists do, according to Dr. Herman Kattlove, a retired medical oncologist. For seven years, he was a medical editor for the American Cancer Society where he helped develop much of the information about specific cancers that is posted on the society's website.

I lost my brother-in-law (my wife's brother) to MDS after he received permanent seed implants for "early" prostate cancer treatment. Urologists can hardly hold themselves back and are out with all sorts of treatments. Sometimes, while a life may be saved, a life may be taken. I have experienced for the second time in my life, the issue. It does happen, but no one emphasizes that point. I will.

[gdpawel]

The New England Journal of Medicine has four perspective pieces on the new US Preventive Services Task Force's prostate cancer screening recommendations:

One, on "what the USPSTF left out," states:

"Although the USPSTF explicitly does not consider costs, policymakers cannot ignore economic aspects of screening. Using data from the European screening trial, researchers have estimated that $5.2 million would have to be spent on screening (and the interventions that follow it) to prevent one death from prostate cancer. That estimate does not appear to include the costs of excessive serial PSA testing and repeated office-based encounters devoted to discussions about screening or interpretation of fluctuating PSA results. The extraordinary time, effort, and costs associated with the PSA-screening enterprise must be evaluated against other claims on health care spending and physicians' time and energy. We believe that the current PSA-based screening paradigm does not compare favorably with competing health care priorities."

[url]http://www.nejm.org/doi/full/10.1056/NEJMp1112191?query=featured_home&

Another, by Drs. Michael Barry and Mary McNaughton-Collins of the Foundation for Informed Medical Decision Making,argues for a grade C recommendation rather than the grade D recommendation the Task Force supports:

"A grade C recommendation would allow the patient to be involved in the decision to skip or choose a PSA screening test, after a discussion with a primary care provider about the magnitude of the known harms and the potential for some benefit. The patient could then provide his perspective on how he views the trade-off. Weighing the pros and cons to make a decision about PSA screening is an individual process, and different well-informed men will make different decisions. A grade D recommendation removes the patient from the equation and puts the physician in the central position of discouraging use of the test. Uncertainty in medicine is more common than we usually let on, and the way to address uncertainty is to allow patients the central position in decision making. A grade C recommendation would acknowledge that whereas the evidence shows that the harms may outweigh the benefits on a population level, some individual patients will still elect PSA screening. We do not believe that anyone but the patient should decide whether the small and uncertain benefits of PSA screening are worth it.
...

To make a grade C recommendation appropriate, we primary care clinicians must ensure there is no more routine, indiscriminate PSA screening -- and no washing our hands of responsibility once the patient is referred to a specialist for prostate-cancer treatment. We owe it to our patients to provide them with the kind of guidance about this screening test that they need and deserve. That's the way to help put the controversy to rest . . . one man at a time."

[url]http://www.nejm.org/doi/full/10.1056/NEJMp1111894?query=featured_home

A third piece recommended:

"PSA screening should not be dismissed as uniformly nonbeneficial. Rather, decisions about screening should be made on an individual basis, by an informed patient and his clinician, after weighing that patient's particular risk factors."

[url]http://www.nejm.org/doi/full/10.1056/NEJMp1112140?query=featured_home

The fourth piece "begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations."

[url]http://www.nejm.org/doi/full/10.1056/NEJMcp1103642?query=featured_home

The DECISIONS study found that “most prostate cancer screening decisions did not meet criteria for shared decision making because subjects did not receive balanced discussions of decision consequences, had limited knowledge, and were not routinely asked for their preferences.”

[url]http://www.ncbi.nlm.nih.gov/pubmed/19786681

A new analysis published in the Annals of Family Medicine,”Primary Care Physicians’ Use of an Informed Decision-Making Process for Prostate Cancer Screening,” found that 24% of primary care physicians who responded to a survey said they ordered screening without discussing it with patients.

[url]http://annfammed.org/content/11/1/67.full

Source: HealthNewsReview.org

[gdpawel]

In many cases, men with a high Gleason score have not seen their cancer spread while men with a low Gleason score have.

This is why the Preventive Services task force no longer recommends the PSA test followed by a biopsy to check the Gleason score.

The American Joint Committee on Cancer (AJCC) issues guidelines for staging cancer (predicting if it will spread and how quickly).

What scientists, who are looking at medical evidence, say about Gleason scores tell us: Although the Gleason score is the standard grading system, studies have found problems with interobserver variability of this score. Aggregating scores into the 3 categories of well, moderate, and poor differentiation improves reliability.

Another problem is the agreement between Gleason scores based on biopsy specimens and scores based on larger amounts of tumor on surgical pathology specimens. One study found 74% agreement within a Gleason score of ± 1 between prostatectomy and biopsy specimens. The number of specimens overgraded and undergraded was similar.

If an asymptomatic man is told he has a Gleason score of 8, and on that basis, goes ahead with surgery, there is a 1 in 200 chance that he will die of complications from that surgery. The odds that a man experiencing no symptoms will die of prostate cancer are much lower.

If he undergoes radiation treatment the odds that he will wind up impotent or incontinent are much, much higher than the odds that he will die of prostate cancer.

But once he is told his Gleason score and told that according to the AJCC - this is the single most important predictor - and is not told that Gleason scores are not terribly reliable, have serious "limitations" and in many cases the Gleason score "overgrades" the cancer, the patient who is told his Gleason score is high is likely to feel that he must go ahead with treatment.

Psychologically, it is very difficult for many men to choose "watchful waiting" even though the medical evidence says that this is the prudent course.
The is why even the American Cancer Society (ACS) no longer recommends routine PSA testing and biopsy - to discover Gleason score.

Instead the ACS says that a physician should describe the risks of PSA testing, as well as possible benefits, going through all of the medical evidence with the patient in a process called "shared" decision-making and then let the patient decide.

But the doctor should not recommend the PSA test and the biopsy that follows.

From the medical journal Radiology:

"Our ability to predict biologic aggressiveness of tumors is still based on the histologic appearance of prostate cancer as assessed with the Gleason grading system, which has substantial limitations."

Thanks to Maggie Mahar at HealthBeatNews