Prostate Cancer Screening: Seduction Of The Innocent

5/28/14

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millions of dollars. TAP wound up paying $875 million—at the time, the largest criminal and civil settlement in the pharma industry’s history.

Prostate cancer treatments have helped fuel the explosion of our nation’s health care costs. It turns out that 85 percent of all radical prostatectomies in the U.S. are done using surgical robots, which cost about $2 million apiece. Studies showed that while men having robotic surgery require less blood transfusions and get out of the hospital sooner than with conventional therapy, there was no difference in cancer recurrence rates. However, men who had robotic surgery had a higher incidence of complications (e.g., incontinence and impotence) than men who had conventional surgeries. The FDA approved the da Vinci surgical robot based on data generated by gall bladder removal surgery, not radical prostatectomies, but prostatectomies are where the big money is made.

Who else profits? Proton beam treatment of prostate cancer, in theory, causes less injury to tissues surrounding the tumor than conventional radiation therapy. According to Ablin, however, there is no data to support the idea that proton beam therapy is more effective than conventional radiation at treating prostate cancer, even though it is much more expensive (78 percent more per Medicare patient). The incidence of side effects is equivalent to what is seen with conventional treatments. Furthermore, proton beam therapy centers could not survive without the income from treating prostate cancer patients. They’d go out of business if the reimbursement rate for proton beam therapy were reduced to what is paid for conventional treatments.

Why was Ablin opposed to approval of the PSA test for the detection of prostate cancer? He gives four reasons:

1) PSA measurements cannot diagnose prostate cancer; the enzyme is secreted by normal, benign, and cancerous prostate cells. PSA levels are affected by many factors, including sexual relations, exercise, prostatitis, and benign enlargement of the prostate.

2) There is no specific level of PSA that detects prostate cancer. Though the original number chosen as a cutoff level was arbitrary, this number was later reduced, leading to even more men being treated.

3) The PSA test cannot distinguish between prostate cancer that is slowly growing or very aggressive. The vast majority of men diagnosed with prostate cancer will die of some other cause before their cancer can progress and kill them.

4) Prostate cancer is an age-related disease; men have a 3 percent lifetime risk of dying of this disease. While 30,000 American men die of prostate cancer every year, the vast majority have localized cancers that never metastasize, and these men eventually die of other causes. Biopsies done on men who died of other causes indicate that 45 percent of men aged 50 to 59 have prostate cancer; this number rises to 65 percent for the 60 to 69 age bracket. These data are independent of PSA scores. As a result, many doctors take a watchful approach to treating prostate cancer, with no interventions (usually biopsies). Ablin claims that most of the one million needle biopsies and 100,000 radical prostatectomies performed in the U.S. each year are unnecessary.

So how did the PSA test win approval for the detection of prostate cancer? According to Ablin’s detailed recounting of the FDA Advisory Board meeting, the test won the vote of the advisory panel only with a number of significant conditions attached. However, these provisions were then dropped when the FDA approved the test. At the Advisory Board meeting, Steven Woolf, science advisor for the U.S. Preventative Services Task Force, stated, “the positive predicative value of the PSA screening is only 1.9 percent. That means that at least 50 men with elevated PSA will undergo unnecessary workups for every man with a clinically significant case…It might be worth subjecting this many men to unnecessary treatment if we knew that one man with cancer would benefit from early detection. But this leads to the second problem with PSA screening: lack of proven benefit. There is simply no evidence that early detection of prostate cancer improves the health of patients.”

Two clinical studies published in 2009 in the New England Journal of Medicine assessed the overall usefulness of the PSA screening program. Their conclusion: “PSA-based screening results in small or no reduction in prostate cancer specific mortality.” These results led the U.S. Preventive Services Task Force to recommend in 2011 against routine PSA screening. According to Task Force co-chair Virginia Moyer, “the bottom line is that science tells us there is very little benefit and significant harms associated with mass routing screening.” This recommendation was met by outrage by a number of groups, including the American Urological Association. However, by 2013, the AUA changed its recommendations regarding the use of the PSA test for screening.

I’ve focused here on the PSA test, but the value of other large population screening tests have also been called into question. Examples include genes associated with increased risk of developing breast cancer, the recent approval of a test for human papilloma virus that some worry may displace the standard Pap test in cervical cancer screening, and direct-to-consumer genetic testing. If you’re considering taking a screening test, it’s a good idea to follow the science and an equally sound notion to track the money. How clear-cut are the screening results, and who bears the responsibility for their interpretation? Who stands to profit if a screening test becomes widely adopted? Don’t be seduced by the mythos conveyed by your physician’s white coat. As Otis Brawley, the chief medical officer of the American Cancer Society put it, “We in medicine need to look into our soul and we need to learn the truth. If your income is dependent on you not understanding something, it is very easy not to understand something.” Patients need to recognize that they need to be their own best advocates for their medical care. You shouldn’t automatically suspend the thinking process just because your doctor has told you something, and this involves more than just getting a second opinion. Sometimes you need to ask your physician hard questions, even if it’s not in your nature to do so. The life you save may be your own.

Stewart Lyman is Owner and Manager of Lyman BioPharma Consulting LLC in Seattle. He provides strategic advice to clients on their research programs, collaboration management issues, as well as preclinical data reviews. Follow @

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  • David Miller

    It’s unfortunate Xconomy chose to print this article. It would be even more unfortunate if the men reading it chose to not get a PSA test as a result. The single best predictor of prostate cancer death is a baseline history of PSA tests in your 40s.

    A man in his seventies with male relatives who lived into their 90s probably has 10-15 years of time left — time that would be extended if he catches his prostate cancer early and time that would be robbed if he quits getting his PSA and develops metastatic prostate cancer.

    Does the medical community overtreat prostate cancer? The popular answer is yes. And I’m willing to grant this premise, as long as everyone understands no urologist ever tied a dude to surgical table and took his prostate out by force.

    If you smash your thumb with a hammer, it sure is easier to blame the hammer than your bad aim. But nobody seriously wants to ban hammers. They understand blaming the tool is useless. It is, after all, just a tool.

    The PSA test is a tool. It is a tool designed to start a conversation. That conversation may end up with the patient, deciding for HIMSELF, to undergo a prostate biopsy to learn more.

    The biopsy is an exceptionally low-risk, but not no risk, tool. It will create another conversation that may end up with the patient, deciding for HIMSELF, to undergo some sort of treatment for prostate cancer. That decision will be made with the best information at hand, even though the best information the medical community can provide is always going to be imperfect. This is, after all, cancer. And we don’t know everything there is to know about cancer.

    Doctors can’t, for example, predict with certainty whether the cancer detected by the PSA tool and confirmed by the biopsy is aggressive or not. Doctors can provide odds, but we as humans aren’t very good at figuring odds when death is involved. We tend to like living as long as possible, so we humans tend to like to eliminate potential causes of death when we can. This is why most of us don’t face jump, paddle across an ocean on our own, or play in a busy street. It’s also why many men who have, by doctors’ best guesses, “low risk cancer” decide to have their prostates removed.

    There are some people, however, who think it is their job to make medical decisions for us men. They believe, without knowing my family history, that if I’m 70 years old I’ll be dead soon enough. And since I’ll be dead soon enough, they believe I shouldn’t be treated for prostate cancer.

    Nobody wants to come out and say THAT, though. They’d be accused of being ageist. Or advocating for “death panels” (whatever the hell those are).

    Instead, they say “You shouldn’t get this PSA test”. You need to understand the central reason why these folks hate the PSA test. You need to understand the PSA test has never killed anyone.

    When someone tells you that you shouldn’t get a PSA test, what they are really saying is “You aren’t worth treating for prostate cancer because you’ll be dead soon.” Because let’s face it, prostate cancer is primarily a disease of old men. Prostate cancer clinical trials have a median age around 70.

    The USPSTF, the AUA, and the ACS all chose to ignore one salient point when creating their guidelines: Death from prostate cancer have fallen dramatically since PSA testing became widespread in the US. Very few men present with metastatic disease in the US. Men instead die of something else because, of course, we all die in the end.

    The PSA test is a tool. You can make bad decisions based upon this tool, just like that hammer can mash your thumb. But it’s not the PSA test’s fault. Therein lies the fatal flaw in the argument against why men should take the PSA test. Make use of this tool, I urge you. Then use the tool as one part of a smart, informed decision-making process. Abandoning regular PSA testing simply means you’ve allowed these folks to make the decision you’re “too old” to be treated for prostate cancer.

    Here’s a couple of other perspectives:
    http://urologytimes.modernmedicine.com/urology-times/news/great-prostate-cancer-hoax-call-arms?page=0,1#sthash.1mKV3kpU.dpuf

    “Prostate cancer will not go away if we simply stop looking for it. Sure, I would theorize that if we were to universally stop checking PSA today, we
    would see a dramatic decrease in the incidence of the disease that would
    be nothing more than a reverse of the spike in incidence seen soon
    after the test’s widespread implementation.

    “But then what? Ten years from now, the number of men presenting with
    late-stage disease diagnosed by obstructive voiding symptoms or bone
    pain would increase and, barring a medical breakthrough, there would be
    nothing we as urologists could do to cure these patients. An entire
    generation would be lost to prostate cancer before the politicians and
    bean counters of the world awoke to the gravity of their mistake…”

    NCCN Guidelines on PSA testing

    http://www.ajmc.com/conferences/NCCN2014/New-NCCN-Prostate-Cancer-Screening-Guidelines-Aim-for-Middle-Ground

  • William Utz MD

    PSA is a Kallikrein serine protein made by prostate cells, both benign and malignant. It’s hardly some mystical conspiracy as suggested by th author re: it’s use and I remain perplexed that such an equally biased article, purports it to be such a worthless, or worse, test based solely to make urologists, radiotherapists and medical device Co’s $. Every urologist and primary care physician I know (practice in MPLS) understand it’s a biomarker that represents an organ-specific condition, not disease-specific. Over the last 2 decades, it is part of the evaluation that urologists have used to lower prostate cancer death rate from @ 45,000/yr men to 30,000/yr since it’s inception into clinical practice…something the author erroneously forgot to mention. He also forgot to mention the ERSPC trial by Schroder, et al, initially published in NEJM in 2009 (and updated in 2012) that found a 30% reduction in prostate cancer death in screening of 162,000 European men since 1991. Instead, I suspect he relied on the heavily flawed (and universally panned) PLCO trial that had significant contamination in both the prescreening and control arms.
    Likely any screening test, one must be selective in whom to offer it to. Routinely, urologists (AUA guidelines) do NOT recommend using the test in men over 70 (55yr-70yr); however, as in the first comment made to this article by Mr Miller, if I have a 71 yr old male in my office who is with his 92 yr old father, whose brother died of prostate cancer (this scenario occurred last wk in my office), I discussed the merits of PSA screening and offer it as a clinical component to determine PC risk. In this setting, his PSA was below the norm for a man in his age group and with a concomitant prostate exam that was nonthreatening, he left my office without a prostate biopsy, knowing his prostate cancer risk was low. He also understood annual PSA’s are NOT necessary as the fore mentioned screening trials lengthened interval PSA testing.
    Lastly, the comment by Mr Miller re: utilizing PSA in men in there 40′s is, in fact, quite engaging. Again, the author of this hatchet job article may wish to enlighten himself to a critically important paper written in 2008 called the Malmo Preventive Preventive Medicine Study (Ulmert, et al BMC Medicine) that demonstrates the point made by the well informed first commentator. It’s a fascinating, thought provoking read and suggest Mr Lyman read it, might enlighten him to a topic he has remarkably failed to understand.
    And one last suggestion. Would change the title of your article to “Prostate Cancer Screening: Seduction of the Village Idiot Reviewer”

  • daviesbj

    Friends,
    David Miller is a brilliant mind and although he has yet to take me to dinner, give me stock tips, or hug me – we have over the years shared a laser like focus on responding to these pseudo-intellectual ventures on the interwebs. Just because this blogger can cite a few NEJM articles and pronounce adenocarcinoma without gumming it all up doesn’t mean that this blog is helpful, meaningful, or instructive. How then can an academic urologist (with no financial ties to pharma or genomics companies) offer a more a balanced approach to this fraught issue?
    The easiest way for the lay public to look at prostate cancer screening is to simply look at the numbers. Have prostate cancer deaths plummeted since the start of PSA screening –> answer…A massive yes. Have the number of men with metastic disease and prostate cancer plummeted since the start of prostate cancer screening?–>….answer…another massive yes. Does that mean that urologists have universally been beneficent healthcare providers with no financial skin-in-the-game. Of course not. Academic urology has carefully crafted protocols to safely watch men whom have been diagnosed with slow-moving prostate cancer. And while the community has been slow to adopt such methods new technologies like mpMRI and genomic testing will lead the way for more thoughtful treatment in the future.
    Simply stopping testing PSA – as the USPTF and others have suggested – is a profoundly dogmatic approach. Like most things in medicine equipoise is needed. Many men whom have limited life expendancy and need not get PSAs – however, many healthy men should get PSAs and will unquestionably benefit from definitive therapy. I can easily (and with better prose than this blogger) trot out the evidence for effective PSA screening. I can easily asssail the United States PSA screening trial for the 25% contimination rate. I can call to task the USPTF for having not a single cancer physician on the panel – AND – for them ignoring careful screening modeling (Etzioni) that while used for breat cancer recs was ignored for PSA recs.
    Still many people do not want to be convinced. They enjoy the lazy intellectual comfort of relying on the USPTF pediatricans and family doctors for advice. They are satisfied that the new medical meme of “overtesting” applies to PSA screening and with that they scurry off to the recliner with beer in-hand, there undiagnosed prostate cancer neatly ensconced in the pelvis propped on the couch – hidden, silent, and deadly.

    Benjamin J. Davies
    Associate Professor of Urology
    University of Pittsburgh
    Fellowship Director, Urologic Oncology
    Chief of Urology, Hillman Cancer Center UPMC

  • David Miller

    Drs. Davies and Utz both mention “contamination” in their criticisms of the two studies primarily relied upon by the USPSTF, the book author, and the article author. I thought I’d chime in with an explanation (all of us deal with this so often, we often use shorthand to describe issues and forget our shorthand is often non-obvious).

    “Contamination” means the control arms of these studies (men who were not offered screening) actually sought screening on their own. This is a big flaw in these trials. The trial intended to test screening against no screening. What it tested was screening against less screening. The resulting effect is to narrow the benefit of screening in the outcomes of the trial.

    Of interest, both the AUA and USPSTF refused to look at epidemiological data when forming their guidelines. These are the data both doctors’ comments cite showing a big decrease in US men presenting with metastatic disease and a big decrease in the number of men dying from prostate cancer once screening became widespread. These are population data, not clinical trial data. Or, if you like, the forest instead of the trees. Both the AUA and USPSTF looked only at the trees.

    Bottom line, men please continue to get yourself PSA tested. Women, please continue to pester men in your life to get PSA tested.

    David

  • Tim Bartik

    This post does not present a balanced view of the situation.

    There are two main studies of prostate cancer screening, one in the U.S. and one in Europe. If you believe the U.S. study, there are no benefits to prostate cancer screening. If you believe the European study, there are benefits to prostate cancer screening, and under some reasonable simulations using the European results, prostate cancer screening and the resulting treatment may have a reasonable benefit-cost ratio, in the sense that some men based on these data would choose screening and treatment.

    For example, Etzioni and her colleagues have done projections using the European study that suggest that in the long-run, screening and the resulting treatment end up saving 1 life for every additional 8 men treated.
    http://journals.lww.com/lww-medicalcare/Abstract/2013/04000/Limitations_of_Basing_Screening_Policies_on.2.aspx

    Because perhaps half the men treated suffer significant side-effects (impotence or incontinence), there are 4 men harmed for every 1 man helped. On the other hand, many men may consider death a more serious harm than impotence or incontinence.

    Other work by Etzioni suggests that screening can do better than this harm-benefit ratio if screening is done on less frequent intervals and uses a higher cut-off before ordering biopsies done.

    Of course, all these simulations assume the European study is right, and the U.S. study is wrong. There is a vigorous scientific debate, as yet unsettled, over the relative scientific merits of the methodologies used in the two studies. Neither study is perfect. However, the above article is misleading because it suggests that the scientific evidence on PSA screening has been settled, and the evidence conclusively points against screening. That is not the case.