A dozen years might seem like a publishing eternity, but the European Journal of Cancer
has decided to purge a duplicate paper from 2000. The article, on the utility of the prostate-specific antigen (PSA) test for detecting prostate cancer, comes from a group whose work in this area has been widely cited as evidence for the benefits of the highly controversial screening tool.
“Prostate cancer screening in the Tyrol, Austria: experience and results,” by a group of Austrian researchers, has a rather complicated past. It’s been cited 42 times, according to Thomson Scientific’s Web of Knowledge. Here’s the notice, which appeared in a recent issue of the journal:
This paper has been retracted at the request of the Editors of the European Journal of Cancer and the authors of the paper.
The paper was published as part of a special issue of the European Journal of Cancer which summarized the proceedings of the 1st International Conference on Tumour Genetics and Prevention, which took place from 17th to 19th February 2000 in St. Gallen, Switzerland. The paper describes the presentation of the authors at the conference. It has become necessary to retract the paper from the European Journal of Cancer because it is also a duplicate of a paper published in the journal European Urology in 1999 (W. Horninger, A. Reissigl, H. Rogatsch, H. Volgger, M. Studen, H. Klocker, G. Bartsch, Prostate cancer screening in the Tyrol, Austria: experience and results. Eur. Urol., 35 (1999) 523–538, doi:10.1159/000019893.
According to the study:
These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.
That might not be the only time this work has shown up in the literature, either. We found a 1997 paper in the journal Cancer by the same group of authors with an awfully similar title, “Prostate carcinoma screening in the county of Tyrol, Austria, Experience and Results.” And as the introductory text states, the work was “Presented at the American Cancer Society Workshop: Review of Current Data Impacting Early Detection Guidelines for Prostate Cancer, Phoenix, Arizona, March 10-11, 1997.”
The conclusion:
These data suggest that PSA-based screening increases the detection rate of clinically significant and organ-confined tumors. Percent free PSA and PSA transitional zone density provide an additional diagnostic benefit over total PSA.
We asked Arnon Krongrad, a urologist who helps run the “New” Prostate Cancer Info Link, whether he thought the retraction would have much of an effect on practice:
Tyrol is seen by some as the prostate cancer “Framingham,” along with its mini-me, the Puget Sound observational studies. [Ed: The NIH-funded Framingham study began in 1948 and has informed a good deal of cardiovascular health care.] I would guess that most don’t think much about Tyrol these days given the noise made by more current studies. So for this reason alone, I’d guess a retraction in a journal few Americans read will have negligible effect on behavior.
Behavior will also be minimally changed, I believe, because behavior is rarely explained by rational analysis and/or consumption of truth. More to the point, it hinges on packaging, marketing, hype, commercial agenda, politics … Otherwise, how to explain the popularity of selenium, pomegranates, proton beam therapy, robots, bottled water?
PSA testing has, in primary care, been extraordinarily popular since the late nineteen eighties. According to the research, it has been worse than useless. Many people have been identified as having prostate Ca and treated with a wide variety of invasive modalities, with little effect on mortality and a dramatic degree of treatment related morbidity. This is because prostate Ca tends to be an indolent disease, hence the aphorism, “more men die with prostate Ca than from prostate Ca.”
Nonetheless, doctors have continued to order the test in all and sundry. Why?
There have been many anecdotes about lives “saved” by PSA testing followed by urgent treatment of previously unsuspected high grade tumors–directly contradicting the statistics but forming a meme (did I just use that word?) justifying continued testing by primary care practicioners who fear accusations of malpractice and negligence.
An example of the availability of good research having no effect on clinical practice.
So the retraction of this old study doesn’t have much effect, especially since it is duplicative. The study does demonstrate the problem: of patients with elevated PSA, only 25% of biopsies showed prostate Ca. Use of refinements like percent free PSA and transitional zone density reduced negative biopsies by 25-30%, but there were still a lot of “dry taps.”
Biopsies have a certain degree of morbidity as well as discomfort(pain) and embarrassment. All the medical activity generated–referrals, ultrasounds, and biopsies followed by radical prostatectomy or radiation–was expensive but didn’t seem to reduce mortality according to more recent research, if I recall correctly.
On the other hand, when I was a student, if I didn’t do a rectal exam on a particular patient, the attending would make me go back and do it; so it got to be an automatic part of my physical. Later, I had a number of patients with normal or minimally abnormal PSA who had palpable hard nodules in their prostates(I’m reversing the order here; I ordered the PSA because of the physical findings.) These patients all had prostate Ca. So I never really trusted the test. On the other hand, I had some patients without nodules who had markedly abnormal PSA; they had Ca too(I ordered the test because they were high risk, in many cases elderly black males.)
Now I don’t trust anybody or anything. But I do take a statin every day.
I agree with Conrad. This retraction doesnot have any significant influence on PSA testing/screening. Yes, the screening itself is controversial – there were false positive cases as well. I am surprised that even after this ambiguity, we didn’t come up with a better marker for prostate Ca. We cannot probably depend on a single marker for a particular disease -unless we are 100 % sure. It is interesting to note that as a physician,Conrad himself doesn’t believe in the test. Dr. Ablin who discovered PSA doesn’t believe either (http://www.nytimes.com/2010/03/10/opinion/10Ablin.html). I don’t believe that I have high cholesterol but the doctor says if I don’t take statin i will die of CVD in another 10 years. Life goes on. After reading retraction watch blogs, I am becoming more and more skeptic about fast-track and high profile publications (not that papers published in lower impact journals are trustworthy either).
Thanks to Ressci for agreeing with me…but about statins: I don’t believe in cholesterol numbers either. What I do believe in is total mortality, and Lipitor did reduce total mortality (as an end point) at least in one pretty good study. Now if I could just keep from being run over by that bus…
Yes, this duplicate study had to be retracted, even if it’s a little late. Now on to the next problem.
I see this retraction as a matter of principles: duplication papers should be retracted, full stop.
Whether this retraction will have any effect on the rates of PSA testing around the world is a question of evidence-based practice which will depend on a proper evaluation of all available evidence (i.e. not only Tyrol).
I believe there are many more duplicates by this group.
Got to http://www.vbi.vt.edu/resources_and_tools
open http://spore.vbi.vt.edu/dejavu/
click on “this link”, i.e. http://spore.vbi.vt.edu/dejavu/duplicate/
enter Bartsch G in the search box, then press search.
Most, not all the duplicates are Bartsch G.
Click on the blue numbers in the ID column to see the comparisons side-by-side.
Be sure to scroll to the bottom of the page to see this.
Duplication paper retracted as a principle? – Preposterous – duplication is the basis of scientific rigor. In fact MORE papers should be published that try to duplicate major studies that influence a large shift in the way we diagnose and treat disease. Unfortunately most journals find duplication studies “boring” and not worth publishing.
Replicated by others surely? Not simply printing something twice.
Senior author on the Eur J Cancer retraction, Georg Bartsch, is mentioned in 2 Nature reports from 2008.
Published online 14 August 2008 | Nature | doi:10.1038/454922a
http://www.nature.com/news/2008/080820/full/454922a.html
“Report finds grave flaws in urology trial”.
“Strasser, who is head of the urology department’s incontinence division, designed and led the stem-cell project and is implicated throughout the report. The university hospital has now forbidden him from treating patients. But, controversially, the report exonerates the head of the urology department, Georg Bartsch, even though he signed many of the documents related to the therapies and is listed as a co-author on the publications.”
“Bartsch, an oncologist, dissociates himself from all parts of the trial, saying that he was unaware of the problems developing until the rector informed him of concerns in November 2007. Although the Lancet paper lists him as one of five co-authors who did “all investigations and treatments”, and includes his signature of agreement, Bartsch insists he did not request authorship but that Strasser included him “in honour of my seniority”. On 31 July Bartsch asked The Lancet to withdraw his name, as “Strasser had not retracted the article as I had suggested”. Bartsch adds that the agency’s report “is not a legal document in any case”.
Bartsch says that ‘honorary authorship’ is given on occasion within his department. He was a member of the university ethics committee until 1997 and, in 2001, he headed an ad hoc committee that oversaw the introduction of ‘good scientific practice’ in the faculty of medicine. Three years later the university’s senate approved a ten-point protocol along these lines, including an explicit rejection of honorary authorship.”
Nature 454, 917-918 (21 August 2008) | doi:10.1038/454917b; Published online 20 August 2008
http://www.nature.com/nature/journal/v454/n7207/full/454917b.html
“Scandalous behaviour”.
“According to a report from the Austrian Agency for Health and Food Safety, a urologist at the university, Hannes Strasser, has conducted a high-profile clinical trial so inappropriately that it must be considered entirely invalid (see page 922). Moreover, that trial represents just a fraction of the total number of patients who paid handsomely for the stem-cell treatment for urinary incontinence without knowing it was experimental.
Strasser’s department chair, Georg Bartsch, insists that he has no connection with, and no responsibility for, the scandal — despite having ‘honorary authorship’ on all the relevant papers, a practice that contravenes the university’s code of practice. And Strasser himself has written an open letter to university authorities denying any wrongdoing.”
I was being sarcastic.
Dear Dmitriy, I was being concrete. My apologies. It creeps up on one with age.
There are two more retractions by this group:
1.Transurethral ultrasonography-guided injection of adult autologous
stem cells versus transurethral endoscopic injection of collagen in
treatment of urinary incontinence.
Strasser H, Marksteiner R, Margreiter E, Mitterberger M, Pinggera GM,
Frauscher F, Fussenegger M, Kofler K, Bartsch G.
World J Urol. 2007 Aug;25(4):385-92. Epub 2007 Aug 14. Retraction in:
World J Urol. 2010 Oct;28(5):663.
PMID: 17701044
2. Autologous myoblasts and fibroblasts versus collagen for treatment
of stress urinary incontinence in women: a randomised controlled
trial.
Strasser H, Marksteiner R, Margreiter E, Pinggera GM, Mitterberger M,
Frauscher F, Ulmer H, Fussenegger M, Kofler K, Bartsch G.
Lancet. 2007 Jun 30;369(9580):2179-86. Erratum in: Lancet. 2008 Feb
9;371(9611):474. Retraction in: Kleinert S, Horton R. Lancet. 2008 Sep
6;372(9641):789-90.
Hannes Strasser had patients pay handsomely for stem cell injections when this therapy was still experimental? That reminds me of the behavior of WPI in Las Vegas: they sponsored a test for XMRV and charged as much as $2400 for it, when there was no confirmation of the supposed connection to CFS/ME. There oughta be a law… the loophole is that whatever you administer, it doesn’t have to be FDA approved if you’re a physician and you personally produce the tx you administer. See also the anti-neoplastons(?) against which FDA has been fighting a losing battle for many years…there oughta be a law…
Dear Conrad Steitz,
Hannes Strasser and Georg Batrsch were in Innsbruck, Austria. The FDA’s writ does not run there.
Kaiser Franz Joseph was according to many stiff, but kindly. Many of the laws from that time still stand.
Post WWII a system of Proporz, consenual government, with both main parties in power most of the time, has been in place.
http://en.wikipedia.org/wiki/Proporz.
Certainly an improvement on the inter-war strife,
http://en.wikipedia.org/wiki/Austrofascism
but many believe that Proporz has led to patronage and nepotism, and stagnation.
Perhaps this was a manifestation of that.
Dear Bernard:
Thanks for the capsule on recent Austrian history. Franz Joseph, I heard, was a nice guy, as kaisers go.
So, the peaceful, prosperous bipartisan government has developed into minor abuses such as patronage and nepotism. Naturally stagnation is a prominent feature when there is no competition. High status medical specialists can probably run wild in this atmosphere.
I would describe a physician personally taking profit from a new product or procedure he has developed as a common, minor, relatively nonviolent form of corruption–graft. Highly unethical. But there should be a regulatory agency, like the Medical Board of each US state.
How has Austria responded to European Union?
In the US, there has been highly variable and ineffective enforcement of individuals who do this sort of thing.
I mentioned anti-neoplastons as a famous example.
As to enforcement actions on large corporations, they are rare, carefully limited when possible, and relatively low cost. Abuses such as the marketing of antipsychotic drugs for use in large populations of nonpsychotic people(such as demented elderly persons), are only lightly punished, even when they lead to numerous deaths. I would call this a violent form of corruption, and drug companies are constantly pushing the boundaries on crimes of this sort.
For example, Abilify, a potent antipsychotic with certain severe side effects such as akathisia, is advertised on television as an add-on for patients who are not responding adequately to their fluoxetine or other antidepressants. How many patients do you think DON’T respond adequately to their antidepressants? A third, sometimes more. What business does a drug company have, advertising on television, targeting an impaired and vulnerable group of patients, offering them another pill? Doesn’t that tend to inflate demand and promote possibly inappropriate pressure on the prescribing physician/provider? What is worse, the patient could be unnecessarily exposed to the risk of some very unpleasant side effects. There is a line between informing the public of available treatment options and pushing a potent drug on a vulnerable population.
I apologize for this rant. I suspect that, although Europe does not have such primitive scams as artificial drug shortages, there may be more subtle but equally pernicious abuses.
Sorry. I should have read the wiki article first–it explains the response of Austria to EU.
“Time spent in reconnaissance is never wasted.”
I don`t know if this is the right place to put it, but here’s another prostate retraction:
http://mcr.aacrjournals.org/content/early/2012/03/20/1541-7786.MCR-12-0085.full?sid=ce8135bd-fbf3-4da5-8d5d-22357a0c9e98
It is about as clear as mud, which is not bad going as some retraction notices are not even that clear.