The problem with scientific mythology


There is an interesting article today in the journal Nature entitled “Science myths that will not die”. It is worth a read.

Among the myths discussed by the author in this article are the following:

  • That antioxidants are “good” for us and that free radical are “bad”.
  • That we humans have exceptionally large brains (as compared to our body mass)
  • That individuals learn best when they are taught in a style they prefer (i.e., verbal vs. visual learning)

and (this is the one many readers won’t like so much)

  • That regular, mass screening for all cancers is necessarily a good idea

In the case of screening, the article makes its case primarily through reference to screening for thyroid cancer in South Korea (but yes, screening for prostate cancer does come up).

10 Responses

  1. Another Myth That Will Not Die — That the PLCO Trial Was a Prostate Cancer Screening Trial That Validly Suggested No Benefit from Screening – And It’s Side-Kick Myth, that the Cochrane Meta Analysis and Other Myth Debunkers Understand Prostate Cancer Science

    Ugh! Here we go with Whack-A-Mole once again!

    It is reasonable to assume that anyone attending to articles on this blog understands that the Prostate, Lung, Colorectal and Ovarian Cancer trial was actually a trial in the US of usual practice for prostate cancer screening, which turned out to involve a high level of screening, versus extra emphasis on screening. A sound interpretation of still very premature PLCO results is that usual care was just about as good as screening (in the days before the blundering recommendation basically against all screening by the US Preventive Services Task Force), which was twisted by those not understanding the disease into the message that screening made no difference.

    Now here is the part of the foregoing article that Sitemaster mentions that relates to prostate cancer screening: “But evidence from large randomized trials for cancers such as thyroid, prostate and breast has shown that early screening is not the lifesaver it is often advertised as. For example, a Cochrane review of five randomized controlled clinical trials totalling 341,342 participants found that screening did not significantly decrease deaths due to prostate cancer1.” Here is the link for footnote 1 to the abstract of the Cochrane review.

    Yes, that number “341,342” participants is impressive. However, what it represents is two large trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the PLCO trial, with other trials contributing a relatively small proportion of the total. The Cochrane analysis does actually recognize that the ERSPC actually does find a benefit for screening, even the relatively porous form used in most of the participating countries (every 4 years or even longer, likely letting many aggressive cancers with short PSA doubling times — a hefty proportion of the dangerous bad actors — slip right through the cracks. However, the Cochrane study faults the ERSPC, and fails to note the highly favorable trend toward screening with the two updates each documenting an additional 2 years of follow-up to this still premature study. In contrast, the Cochrane study misinterprets the PLCO study as a screening versus no screening study, fails to note that, if so considered, the study has an extremely high degree of supposed non-screenees who were actually screened, fails to note the critical pre-maturity issue even if PLCO were a true screening versus no-screening study, and fails to note other flaws. Therefore, if you subract PLCO from the 341,342 total, and if you subtract ERSPC also because it actually shows a substantial and ever-growing benefit to screening, you don’t have much of a number left to support the anti-screening case. Yet the author of the subject article, accepted for publication in the prestigious journal Nature, accepted the Cochrane analysis uncritically! No clue at all!

    Actually, while I find this mangling of the science on prostate cancer screening quite discouraging, I also find it very human and supportive of the author’s thesis about the enduring nature of scientific myth. The journal Nature enjoys a fine reputation, but here we have proof that we cannot park our brains when reading it. I learned that lesson some time ago about the New England Journal of Medicine when it published the original prostate cancer “screening” results in 2009 from the ERSPC and PLCO. There was an accompanying editorial that raised some doubt about maturity of the results, but gross flaws were not spotlighted.

  2. Dear Jim:

    Congratulations. You have just provided a highly precise reflection of one of the other points made by the author of the article:

    “Once a myth is here, it is often here to stay. Psychological studies suggest that the very act of attempting to dispel a myth leads to stronger attachment to it.”

    You may not like this, but just as the data from the PCLO trial were flawed by people having PSA tests out of protocol, the ERSPC trial was flawed by it’s very design. It was actually seven quite separate studies, of which only one (the Swedish/Goteborg set) have shown a result in favor of screening. The fact is that in the past 25 years there has only been a positive result from one screening trial (the Goteborg study). That study was biased by the fact that it was based on an entirely previously unscreened population.

    This does not mean that PSA testing of at-risk patients is a bad idea. It also does not mean that getting a baseline PSA test is a bad idea. It does, on the other hand, mean that we have almost no good data demonstrating the value of prospective, frequent, mass screening of all men for risk of prostate cancer through the use of the PSA or any other currently known test.

  3. One myth that persisted is the “widespread” use of PSA mass screening here in the US. Another is the computer generated unreal rate of PCa over treatment…

    What is real and still unexplained is the reduction in prostate cancer-specific deaths here and elsewhere where PSA has been used to detect prostate cancer and effective treatment has altered the natural course of the disease.

    If the main reason the Goteborg trial was successful is because it was applied to an unscreened population, how do we explain the continued, reduced prostate cancer mortality rate here, where there is “widespread” PSA use? Ah, Mythology at work. Over-treatment of non-significant disease is not causing that. …

  4. Dear Ralph:

    I agree with you, and I think there are four important factors at play here, but the degree to which each one has contributed to the decline in prostate cancer-specific mortality is difficult to assess. However, for whatever it is worth:

    (1) The availability of the PSA test most certainly contributed to increased awareness of male risk for prostate cancer, and thus to the identification of risk for prostate cancer much earlier in the development of the disease in many at-risk patients.

    (2) The average American diet has improved over the past 20 years, and this may have been having an effect on risk for all cancers

    (3) There has been a massive focus on improving the available treatments for localized and more advanced forms of prostate cancer (although I certainly wouldn’t want to suggest that they are close to being as good as we all might like).

    (4) Time from diagnosis to prostate cancer-specific death (among those who die from prostate cancer), on average, is now closer to 20 years than it is to the 5 years that it used to be in the late 1980s (when most men still got diagnosed with locally advanced or metastatic disease). Thus, many men who were diagnosed with localized disease in the early to mid 1990s are still alive today — at least partially because their disease was diagnosed 10+ years earlier than it used to be (lead time bias).

    At least some of the decline in mortality rate is quite certainly associated with the use of PSA testing (as even people like Gilbert Welch are happy to admit). But that still doesn’t imply that mass screening is having (or has had) an overall or a prostate cancer-specific survival benefit.

    I would point out, yet again, that I am a strong advocate for access to PSA testing for those men who want to have such tests, who understand the “slippery slope” that can easily lead to over-treatment, and particularly those who have well-identified risk factors for clinically significant prostate cancer, … but I feel able to distinguish between the known benefits of PSA testing among men with known risk factors (including an elevated baseline PSA level in one’s 40s) and the lack of proven benefits associated with mass, population-based screening.

  5. Dear Mike,

    I am not attributing the decline in prostate cancer deaths solely to PSA testing. Far from it. On the other hand it contributed more to the decline that Gil Welch and others are ready to admit.

    In the absence of PSA testing the disease would be diagnosed in a significant percentage of men at a more advanced stage (this is known from the past when men’s life expectancy was much lower and it should be worse now that we live longer). In such absence or at a reduced rate of PSA use one can expect an increase in deaths such as seen in countries in which PSA use is low. This would make your points 1, 3 and 4 if not invalid at least much weaker.

    You mention lead-time bias but the reduction is deaths are not impacted by this bias. As far as the improvement in treatments for advanced disease, the results are positive but at the same time the medium survival measured in months at most is hard to consider as a major cause of the death reduction. It is (in my estimation) early detection of disease destined to kill and opportune treatment that alters the natural pathway of the disease that has resulted in the major reduction in deaths here. This in spite of a limited use of PSA testing in a significant number of men at risk here in the US (in spite of the widespread PSA use myth).

    I know that you are a strong advocate to access to PSA testing. You are not the problem. The problem is with those that say that that testing does more harm than good. In saying that, the general population has been confused and less men are being tested with PSA these days. The intent is to reduce over-treatment and in doing that sacrificing men to die of prostate cancer more often: a sad solution to a problem that could be resolved with the presently available tools applied with current knowledge and compassion. That is the sad reality these days. …

  6. Ralph:

    Again … I agree with you. This is all because far too many people think about all of this in terms of “screening” (of all men) as opposed to not “screening” (of any men). That “packaging” of the discussion is an inappropriate black/white or do/don’t form of packaging.

    The solution to the entire problem is for everyone to dump the unfortunate and misleading word “screening” and to start talking about individualized testing based on baseline PSA levels and other risk factors.

  7. Dear Sitemaster:

    I’m replying to your fundamental point in the comment dated December 18, 2015 at 7:45 am above that mass screening is not wise, which is my view also. Here is my suggested recommendation, which reflects that view, to the US Preventive Services Task Force Draft Research Plan:

    ‘The US Preventive Services Task Force recommends that informed screening, where intervals are tailored to individuals and active surveillance is emphasized as a key approach if prostate cancer is diagnosed and is characterized as “low risk,” is of net benefit for men with a life expectancy of at least ten years. The Task Force also recommends that uninformed screening is likely to lead to more harm than benefit for most men.’ Just to repeat, these are my suggested words and not those of the Task Force. (This was at the conclusion of 15 pages of comments. They did promise to read our comments.)

  8. Dear Jim:

    Then if you agree with this, which you clearly do, I would strongly suggest that you stop using the misleading term, “screening”, which is very widely interpreted to mean mass, population-based screening, and use the term “informed testing”, which is a great deal more precise and helps us all get beyond the black/white discussion that is at the root of this entire problem.

    Mike

  9. Dear Mike:

    I’m responding to your reply to me of December 19, 2015 at 7:17 am in which you suggested the term “informed testing” instead of screening.

    I like your suggestion and will try it on for size. I have not been fond of “early detection” as a substitute for screening as the objective is really to “test” (already trying) whether there is preliminary evidence of prostate cancer rather than to detect it, which we actually hope not to do. In a sense “early detection” is kind of a turn off to potential “informed testees”. Hmmm. That doesn’t roll off the tongue so well, but maybe I’ll get used to it.

    You have a better sense of the greater prostate cancer community than I do, so I’ll accept your view of the connotation of screening, but for me that word has covered both mass and informed screening for more than a decade.

    PS: I have regularly encountered opposition to “informed screening” or “empowered screening” among adherents to the Task Force’s recommendation; perhaps talking about “informed testing” will improve communication.

  10. Dear Jim:

    The problem with the word “screening” is that it has indeed been used (in my view inappropriately) to describe both the testing of individuals and the mass testing of populations (for risk of all sorts of disorders).

    I would argue that we would all be better off if we limited the term “screening” to the regular mass screening of populations (as in “newborn screening” of all newborn children for a range of possible common and rare life-threatening disorders) and “screening” of all passengers and their baggage at airports before they are allowed on a plane.

    When you think about it this way, the USPSTF is arguably correct that “screening” for risk of prostate cancer using the PSA test should not be recommended, but (as the USPSTF also noted) informed testing of certain categories of individual may be entirely appropriate.

    If we were all to use language that corresponded to this, and explain why in a consistent manner, the black/white dichotomy vanishes, and such language/terminology also helps to explain why “empowered screening” and “informed screening” make no sense to those who do not think that mass population-based screening is appropriate.

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