Category: Informations (en)

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Effect of a mammography screening decision aid for women 75 years of age and older

April 23, 2020

Randomized clinical trial by "cluster" (cluster)

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2764100

 Authors: Mara A. Schonberg, MD, MPH; Christine E. Kistler, MD, MASc; Adlin Pinheiro, MA et al.

A cluster randomization trial is a trial in which subjects are randomized not individually but by randomization unit or groups of subjects, known as "clusters".

Here 546 women aged 75 to 89 years, who received a decision aid on mammography screening prior to a health care visit with their practitioner, constitute the randomization unit.

Purpose of the study :

To investigate how the use of a screening decision aid for women 75 years of age and older affects their decision to participate in mammography screening.

Study Results

Providing these women with a mammography screening decision aid prior to their medical visit helps them make informed decisions and leads to fewer women undergoing mammography screening.

Study Conclusion

Therefore a decision support tool can help reduce overscreening.

Our analysis

Cécile Bour, MD

Such a study could be of interest on younger age groups, although an assessment of what concerned women perceive and the impact of the lack of balanced information has already been carried out [1].

How do women perceive the benefits of screening according to what has been conveyed about it, and according to the information they have received, and which has forged their convictions on the subject?
This is the question posed in this study by Domenighetti et al, according to which the table below was drawn up by Nikola Biller-Andorno, a bio-ethics researcher who collaborated on the work of the Swiss Medical Board. [2] [3]

In this comparative table we can find, in part A, data from Domineghetti's American Women's Perception Survey, and in part B, actual data from the most likely scenarios, found from the most convincing and reliable studies. [4]1-3)

The authors (Biller-Andorno et al.) were stunned by the significant discrepancy between women's beliefs about the benefits of screening and the reality, and legitimately asked the question: how could women make an informed decision if the benefits of the procedure were overestimated?

See our article with the detailed results of this work here: https://cancer-rose.fr/en/2020/12/18/perception-and-reality-2/

For the moment, the decision-making tool for women requested by the citizen consultation is completely absent in France, since 2016 when the consultation took place.

There is indeed a question of establishing one " in the French way ", which will hardly be possible given the deficient epidemiological data in our country [5].

Recently in JAMA a viewpoint was published on recommendations for shared decision making with the patient [6].

Unfortunately at the moment it seems that the shared decision is more a medical " dream " than a reality.

Indeed, recommendations from learned societies always have more weight than the values and experiences of the patient, and are sometimes imposed in the media and on patients with great virulence and authoritarianism, as we saw in 2019 with the abusive campaign of the French national college of obstetricians and gynecologists (CNGOF)[7], advocating the extension of screening to the elderly, without any national or international recommendation. The Council of the Order, which we had alerted, did not react ,[8] even though it regularly calls to order those who violate the communication of verified medical notions, as is currently the case in the Covid context.

To conclude

There is still an enormous amount of work to be done so that the values and reality of each patient's life, including her age, can guide the practice of every physician. There is also a long way to go, to ensure that physicians have the practical means to contribute to shared decision making, so that women, both older and younger age groups, finally have access to real tools made on a correct and independent scientific basis.

The development of such tools implies admitting the possibility of women's refusal to participate in screening, as the performance of mammography screening has proven over the decades and in the course of modern studies to be increasingly disappointing.

The real problem is that neither health authorities nor politicians are prepared to accept the possibility of women refusing to be screened for political and ideological reasons, thus depriving them until now of true autonomy in health.

References

[1] Domenighetti G, D'Avanzo B, Egger M, et al. Women's perception of the benefits of mammography screening: population-based survey in four countries. Int J Epidemiol2003;32:816-821 CrossRef | Web of Science | Medline

https://www.ncbi.nlm.nih.gov/pubmed/14559757

[2] https://www.nejm.org/doi/10.1056/NEJMp1401875

[3] https://boris.unibe.ch/51602/7/Biller-Andorno%20NEnglJMed%202014.pdf

[4] 1. Gotzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;6:CD001877-CD001877 Medline/

  • Independent UK Panel on Breast Cancer ScreeningThe benefits and harms of breast cancer screening: an independent review. Lancet 2012;380:1778-1786 CrossRef | Web of Science | Medline/
  • Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014;348:g366-g366 CrossRef | Web of Science | Medline/

[5] https://cancer-rose.fr/2020/01/22/faisabilite-dun-outil-daide-a-la-decision-sur-le-depistage-du-cancer-du-sein-a-la-francaise-selon-les-criteres-ipdas/

[6] https://cancer-rose.fr/2020/03/14/recommandations-pour-une-prise-de-decision-partagee-avec-le-patient/

[7] https://cancer-rose.fr/2019/04/07/la-campagne-pour-le-depistage-de-la-femme-agee-par-le-college-national-des-gynecologues-et-obstetriciens-de-france-cngof/

[8] https://cancer-rose.fr/2019/05/02/lettre-au-conseil-national-de-lordre-des-medecins-concernant-la-campagne-du-cngof/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Loss of scientific rigor and scientific misuse, poor quality medical research

Cécile Bour, MD, May 14, 2020

In the era of EBM (proof-based medicine), the headlines of last few weeks during the Covid 19 pandemic have highlighted the drifts that undermine this approach of a modern medicine.

We should not only blame the recent context; over the last decade and perhaps more, there are three main problems in modern medicine that Jeanne Lenzer, an investigative medical journalist, and Shannon Brownlee, Vice President of the Lown Institute, « a nonpartisan think tank advocating bold ideas for a just and caring system for health in the United States », have denounced in "Issues" column of their site.

These three drifts seriously weaken evidence-based medicine and jeopardize the benefits owed to patients, and they are currently exacerbated in this period of crisis.

Three main drifts of today's medicine

  • The main drugstore in the city where I practice has the motto "primum non nocere" above the counters. But, according to Lenzer and Brownlee, doctors are insufficiently trained to discern good science from poor studies, and prefer to use molecules they know and whose effect appears biologically plausible. Fear and haste have sounded the death knell for the Hippocratic maxim, a pillar of medicine. Beliefs and unproven faith in medications used for other medical conditions have been considered, without concern for their real usefulness against an emerging and unknown virus, or their possible harmfulness.
  • The second pitfall identified by the authors is the prominent role of the media today. On the one hand,  convictions and opinions of non-physicians are following in the footsteps of politicians, to whom the floor is widely and generously given. On the other hand, many of media that echo this are ignorant and incompetent in scientific method or in search for evidence, and also have a commercial interest in hype around these well-known and popular, but null, town criers.

We can only agree with this observation, having ourselves been confronted with a very unpleasant episode of attacks from a TV host, who mediated his experience of prostate cancer at will to convince people who asked him nothing, to undergo prostate screening test, in spite of all the non-recommendations of such screening [1].
The naive crowds that "follow" these characters, fan clubs generally very well supported on social networks, do not facilitate the expression of cautious doctors or independent collectives like ours, which are inevitably a killjoy in the general hope. The word of the Cassandras is hardly a media-friendly one...

●The third calamity denounced by Lenzer and Brownlee concerns poor quality studies that do not include what is called a "control arm", i.e. inclusion in the study of a comparison group that has not been given the drug being tested. The control arm is the cornerstone of a strong randomized controlled trial. It aims to formally establish the true efficacy of a product, highlighting possible biases in the tested protocol. For example, a drug may appear to be effective in reducing the risk of a given disease when the population to which it was administered is already naturally less at risk, because they are younger, healthier or have easy access to medical care. A control arm with a wide range of subjects can show ineffectiveness of the test drug in certain groups of  population and thus point to errors in reasoning or biases that would go unnoticed. In hastily constructed studies, on the other hand, potential harms may be underestimated. 

But even outside of critical health periods, such as in the field of cancer for example, proclamation of "miracle" drugs has been legion in recent years, with questionable studies, selling hope of so-called "revolutionary" chemotherapies. On this subject read the post of Annette Lexa, our toxicologist.

We add to this last point on the poor quality of medical researchn a particular type of study that is currently spreading, it is the "non-inferiority" test, all the more fraudulent and perfidious that nobody understands a drop.

Doshi and all. 2] studied informed consent forms from non-inferiority studies on antibiotics. Their observations are generalizable, however, because there are many applications of this type of study, in diabetes, cardiology, infectiology and cancerology. Doshi et al. found that often neither the methodological experts nor the members of personal protection committees were able to define the true objective of the study from the information forms given. For the methodologists, only 1 out of 50 trials, according to them, correctly restituted the objective of the study; for the patients, 7 out of 50 studies succeeded in doing it. These results raise the question of whether consent is truly an informed one, and thus whether the trial is even ethical.

But what are we talking about?

Non-inferiority trials

We have given a summary explanation about the MyPEBS study for personalised breast cancer screening which concerns the theme of our site, a study that we have analyzed in depth here: https://cancer-rose.fr/my-pebs/.

In the non-inferiority trial it is a question of comparing two elements (two medical devices or two procedures, or two drugs) to check whether the device or procedure or treatment being tested would not be worse than what is already in use, accepting a certain loss of effectiveness within a certain tolerated margin, known as the non-inferiority threshold.

It is not a question of verifying whether the system, procedure or drug tested would be superior to former one. This is often how the press reports it and how doctors and public understand it, but it is not the case!

For example, for breast cancer screening, intended purpose is normally to reduce severe forms of cancer. In the MyPEBS non-inferiority study, if the new personalized screening tested does not appear to favor a rate above 25% (arbitrarily set threshold) for additional severe cancers, the trial will be declared a success. You have read correctly. There is no control group there either to test what would happen without screening, which would be legitimate though since recent studies on this screening no longer manage to demonstrate a positive benefit/risk balance.

It is true that in non-inferiority trials in cancerology the control arm is rarely considered, this being judged to be unethical given seriousness of disease, and patient cannot be deprived of any care. But here, in the MyPEBS study, healthy and non-complaining women are being tested, we should remember.

What must therefore be understood, in short, is that it is possible, with non-inferiority trials, that a new health procedure can be accepted as effective, even if its therapeutic or beneficial effect is slightly inferior to current standard. In a non-inferiority trial, the new procedure or drug is not supposed to make the participant healthier than she would have been outside the trial, since superiority of the procedure or drug is not sought.

The only assumptions are :

- In the best configuration, participants randomized into the study's test group could fare as well as if they had not participated in the trial,
-or then potentially worse within an arbitrarily accepted margin, in the wrong scenario.

And everyone is happy. The public because they are not well informed and believe that what was tested on them is 'superior', the journalists who did not grasp the subtleties of the methodology and write laudatory articles, and above all the designers of the study. Why is such an approach necessary? Because with this set-up, the study is subtly biased towards the result desired by the promoter, which is to obtain or safeguard a market share much more than to answer a scientific question whose stake is the well-being of the patient. For MyPEBS, the aim is to establish breast cancer screening, since women will only have a choice between two options: old screening or personalized screening, but screening in all cases.

To caricature, the patient or population will be worse or not less well, but the good news is that the study is a success..

Two interesting articles to help the practitioner in the critical analysis of the studies that published

Vinay Prasad, in an editorial in the JGIM[3] (Journal of General Internal Medicine) where he actually quotes the results of Doshi et al, refers to the publication of Aberegg, Hersh and Samore who analyzed 183 non-inferiority comparisons of 163 clinical trials published in the five major impact medical journals.

Aberegg and colleagues found that only 70% of the non-inferiority studies explicitly stated why new therapy would have an advantage, and in 11% of cases no advantage could be inferred. This suggests to these authors that many of these studies should not have been conducted.

What should the practitioner beware of and what trials of non-inferiority can he trust? According to V.Prasad, it is necessary to :

  • Consider whether new therapy is less expensive, more convenient, less invasive or less toxic than old one. If answer is no, stop looking, he says! There must be a positive compensation for the patient for loss of effectiveness of the new procedure or new drug being tested. If not, there is no point in learning about the "novelty".
  • Ask yourself how much loss of effectiveness of the new procedure or new treatment you would be willing to accept in order to adhere to it. 5% loss of effect, or 10%? More or less?
  • Be concerned about the margin of inferiority accepted. E.g. for MyPEBS the non-inferiority threshold is very generous. This means that if, at the end of the new screening, 25% additional serious cancers are found, the study is "successful". This margin would have to be justified, and this justification would have to appear at least in the study protocol, which is not the case.
  • Finally, consider whether the new intervention was in fact 'inferior', not 'non-inferior'.

The French independent journal Prescrire[4] examined  problems of these particular trials in 2006. Their advice is similar to that mentioned above. For the journal, one must be critical of the threshold of non-inferiority that is chosen a priori, arbitrarily by trial designers. For the patient, this threshold is equivalent to the loss that is consented to in relation to the reference treatment or device.  It is therefore necessary to be sure that the result is not in fact a true inferiority.

For Prescrire, in short, these tests are intended to simply exclude the possibility that a treatment or process is massively worse than what already exists. When the treatment or procedure is slightly less effective, and within a certain accepted margin, the new treatment or procedure is only of interest to the patient if it brings other benefits in compensation. And this is where the stick can hurt, as in this study we regularly criticize, and not just us.

To conclude:

The urgency and willingness to obtain results quickly justifies dispensing with well-conducted controlled studies and exposes us, because of flawed and poorly executed studies, to biased medical judgments and erroneous conclusions.

Improper, sometimes excessive, communication by lay people or ignorant media aggravates media coverage of drugs or procedures that we do not know what they actually induce, whether they do more harm than good.

These problems pre-existed before the context of the Covid19 pandemic which only brought them to light.

Research in science is important, yet it must meet quality standards, be done by scientists who are concerned about respecting proven methodologies and meeting standards, and this in a serene media environment.

This is currently not the case, as damage and physical inconveniences to health of populations are aggravated by misinformation and pollution of scientific debate by quarrels of opinion.

If we want to make good science that is useful to people, we must develop a critical spirit, constantly verify results of studies promoted as revolutionary by media, see by which methods conclusions have been reached.

We have come full circle; if we want to make good medicine we will always return to what is proclaimed at the front of the drugstore, the basic principle that must underpin our medical practice: "primum non nocere" .

References

[1] https://cancer-rose.fr/2020/02/06/ah-mais-quelle-aubaine-ce-cancer/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710221/

[3] EDITORIAL
Non-Inferiority Trials in Medicine: Practice Changing or a Self-Fulfilling Prophecy?

Vinay Prasad, MD, MPH

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Department of Preventive Medicine and Public Health, Oregon Health and Science University, Portland, OR, USA; Center for Health Care Ethics, Oregon Health and Science University, Portland, OR, USA.

J Gen Intern Med 33(1):3–5
DOI: 10.1007/s11606-017-4191-y
© Society of General Internal Medicine 2017

[4] La Revue Prescrire avril 2006/Tome 26 N°271, page 249

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Parallel to breast screening, prostate screening: overdiagnosis, as well!

As for breast cancer screening, there is a similar problem with prostate cancer screening.

While there is still a controversy regarding breast cancer screening, as far as prostate screening is concerned, we have crossed this step.

Official recommendations are that mass screening should no longer be offered to men. Yet it is still advocated, in particular by our urologist colleagues.

Philippe Nicot explains in The Conversation, in an article published on November 15, 2016, a summary of the ins and outs. :

https://theconversation.com/prostate-attention-a-lexamen-de-trop-68756

We publish it again here, following the guidelines for republishing issued by The Conversation.

Prostate: beware of over-examination!

Philippe Nicot, University of Limoges

We learn an important news, in the November 15 issue of the weekly scientific publication of Santé publique France. The institution in charge of monitoring diseases in our country slips, with a glint of suspicion, that health authorities have revised their instructions on screening for prostate cancer, the most common cancer in men over 50 years of age. And this on the basis of scientifically founded information. In particular, they are encouraging doctors to prescribe less the blood test that has long served as a justice of peace in deciding whether or not to remove this gland from male genital tract. A small revolution.

 Health authorities are finally opening their eyes to an inadequate practice that has been known and reported by many experts for nearly three decades. Prostate cancer is usually detected by dosage of a protein produced by cells of prostate gland, PSA, or prostate specific antigen (PSA), from a simple blood test. This low molecular weight glycoprotein is one of the constituents of semen, serving to fluidify it and facilitate sperm motility. Some of it passes into bloodstream. Its production is linked to the activity of prostate. In a blood test, a rise in PSA levels is interpreted as an indication of a possible tumor.

In the Weekly Epidemiological Bulletin (BEH) that Santé publique France (formerly the Institut de veille sanitaire) focuses on prostate cancer, the editorialists are prominent guests: the President of the National Cancer Institute (Inca), Norbert Ifrah, associated with the Director General of Santé publique France, François Bourdillon. They note that PSA testing is, according to data from the French National Health Insurance, practiced very frequently. "In 2015, 48% of men aged 40 and over had taken a PSA test in the previous three years, with this frequency rising to 90% for men aged 65 to 79," they say.

However, this analysis in men who do not complain of any signs suggestive of cancer is not recommended in 2016 by "any health agency or authority in the world," they write clearly, neither in a screening program for this cancer, nor at the individual initiative of the doctor. In other words, there is a big gap between official references and practice.

No established effect on mortality

Today, we have necessary hindsight to answer the only valid question: has the generalization of this examination reduced the mortality related to this cancer? The assessment drawn up by the National Cancer Institute (Inca) in 2015 states that it has not.

Two randomized trials conducted in the U.S. and Europe that evaluated the impact of a PSA prostate cancer screening program on specific prostate cancer mortality have produced contradictory and questionable results," writes the health agency. "Their meta-analysis did not show a significant effect in terms of a decrease in mortality from prostate cancer, which does not support a conclusion in favor of a benefit at a population level".
The test also has many disadvantages. It detects cancers that, for some, progress so slowly that regular monitoring would be preferable to surgery - only they cannot be distinguished with confidence yet. The test also has many disadvantages. It detects cancers that, for some, progress so slowly that regular monitoring would be preferable to surgery - only it is not yet possible to distinguish them with certainty. The test poses a high risk of overdiagnosis and overtreatment," says Inca. It detects many cancers that would have remained asymptomatic without having the means to identify cancers that do not require treatment. However, surgery can have serious consequences, rendering the man impotent or incontinent. "The treatments are effective, but their undesirable effects can be significant, while keeping an acceptable quality of life must be taken into consideration," adds Inca.

Based on this observation, Inca took action - without any fanfare - with general practitioners, the main prescribers of this PSA dosage. The agency elaborated with the College of General Medicine documents to allow the National Health Insurance Fund for Employees (CNAMTS) to exchange on this subject with general practitioners. The objective: to make this examination, soon, no longer automatic.

Mass screening not recommended

The PSA assay has been a controversial issue in France since 1989. That year, a "consensus conference" was held in a state-of-the-art manner. Organized by three urologists, Professors François Richard, Guy Vallancien and Yves Lanson, and the economist Laurent Alexandre, this consultation of experts already concluded that "the organization of mass screening for prostate cancer is not recommended".

A new consensus conference is held in 1998 and the same year, a clinical practice recommendation states even more clearly: "Since prostate cancer screening (whether mass screening, directed at the entire interested population, or opportunistic, on a case-by-case basis) is not recommended in the current state of knowledge, there is no indication to propose a PSA dosage in this context. »

Visual of the first National Prostate Day in 2005 by French Urology Association

But then a grain of sand slips into the system. The majority of learned societies and professional groups around the world rule against such screening, except for three American associations (American Cancer Society, American Urological Society, American College of Radiology). Shortly afterwards, the French Association of Urology (AFU), which brings together experts in male reproductive system, launches in its turn what can be described as a campaign to promote PSA testing.

In 2009, however, two major studies, one American and one European, brought the scientific debate to a close. The French National Authority for Health (HAS) concluded: "No new scientific element is likely to justify re-evaluating the advisability of setting up a systematic screening program for prostate cancer using PSA testing. "End of story.

The American physician who developed the dosage in 1970, Richard Albin, is himself concerned about the "public health disaster" caused by his discovery. In an op-ed published in 2010 in the New York Times, he wrote:

”I never dreamed that my discovery four decades ago would lead to such a profit-driven public health disaster. The medical community must confront reality and stop the inappropriate use of P.S.A. screening. Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatments”

A risk of impotence

In 2011, an American authority, the US Preventive Service Task Force (USPSTF), recommends stopping prostate cancer screening with PSA, emphasizing its side effects. For every 1000 people treated, there are 5 premature deaths one month after surgery, between 10 and 70 patients with serious complications but survivors. Radiotherapy and surgery have long-term effects, and 200 to 300 patients will become impotent and/or incontinent.

In addition, there are deaths following prostate biopsy, a far from insignificant procedure. A French study of 2010 conducted by Paul Perrin reports an alarming figure: 2 per 1000.

Today, France has officially ended the systematic use of PSA testing. And the health authorities have decided to rely on general practitioners to change mentalities and practices.

How do you explain the fact that GPs have not taken the lead? Because they are misinformed, no doubt. Because patients are asking them to do the exam, too. The Inca suggests it in its synthesis on the benefits and risks of screening. "According to surveys, one out of every five men over 60 years of age takes the initiative to be screened for prostate cancer," the agency writes. The analysis of practice of general practitioners shows that, torn between the contradictory recommendations of health institutions and several learned societies and sometimes confronted with a strong demand from patients, general practitioners are rather inclined to propose or prescribe a PSA dosage to their male patients. » The time counted, in a consultation, certainly plays a role. Speaking on France Inter in 2011, the general practitioner Dominique Dupagne summed up the problem in a striking formula: it takes 15 seconds for the doctor to explain that this screening should be done, and 30 minutes to explain that it should not be done.

What is the role of urologists?

If it is legitimate to mobilize general practitioners to prescribe the PSA dosage more effectively, what about urologists? Surprisingly, they are not integrated into strategy of health authorities. In order to understand this, it is necessary to look back at the confrontation that has been taking place on this subject for more than twenty years between urologists on the one hand, and epidemiologists and general practitioners on the other.
As early as 1994, the independent medical journal Prescrire testifies to the exchanges between the general practitioners who are members of their editorial staff and the urologist Bernard Debré. The former minister and member of parliament strongly defended screening and stated: "Medical references will come, they will decide that PSA is a fundamental examination after 50 years. "For general practitioner Jean-Pierre Noiry, "this opinion is in complete contradiction with the results of available studies and consensus recommendations".
Thereafter, the tone will not stop rising. Researchers specializing in epidemiology and public health, such as Catherine Hill, Alain Braillon and Bernard Junod, are stepping up to the plate in violent face-to-face encounters with urologists urging the prescription of PSA dosage. Christophe Desportes, a general practitioner in Finistère, in his book Prostate, the big sacrifice (Editions Pascal) tells how in 2005 he challenged a fellow professor of urology, and was retorted: "We're going ahead while waiting for proof of usefulness to be provided". A gamble as daring as that of administering a drug before knowing what it is used for?

Visual of the campaign Touche pas à ma prostate (Don't touch my prostate), launched on the Atoute.org website in 2008.

A committed general practitioner and administrator of a patient community website, Dominique Dupagne decided to publicly call for a moratorium on his website: "Don't touch my prostate! "The watchword circulated among GPs and beyond. But in the field, the battle is far from being won. Urologists have spread, by their authority, the idea that this screening should be carried out from the age of 50. Many patients are adhering to it. As for general practitioners, most follow. Either because they agree with the opinion of specialists, or because they are afraid of a lawsuit brought by a patient. Their fear is fueled by the legal ordeal suffered by a colleague, Pierre Goubeau, prosecuted for not having prescribed a PSA dosage. This general practitioner based near Troyes will finally emerge victorious from a case that will drag on from 2008 to 2015.

No logo of the Urology Association

Today, urologists appear to be the major absentees of the national action that is about to take place. The French Association of Urology (AFU) will not appear on the documents that will be distributed to general practitioners by the Health Insurance. According to Inca, "when consulted, the AFU did not wish to put its logo on the doctor's document, because it felt that the repercussions of this document present the risk of an irrational failure to use the PSA dosage, and of a regression in the stage of revelation of prostate cancers and their survival rates. »

One might think that urology specialists do not wish to see a substantial decrease in their activity. However, this would be reductive. It should not be forgotten that these colleagues are confronted with the difficult image of patients suffering from cancers in serious forms, particularly with bone metastases. I think, having discussed with many of them, that this proximity to the most seriously affected patients makes them hermetic to scientific data that seem far removed from their own experience. If Health Insurance wants to see its action succeed, it will also have to unravel all the threads of the representations of this disease among urologists.

Being too often involved in public health debates, we forget an actor far from playing a marginal role: credit insurers.

Through a quick search on the Internet, I was able to verify that many of them ask for this test before accepting the subscription for men over 46 years old. While it seems legitimate for insurers to seek to limit the risk of default for their clients, they cannot tolerate exposing them unnecessarily to significant side effects.

The public health action plans to "provide men aged 40 and over with balanced information on the advantages and disadvantages of screening to enable them to make an informed decision". If I may make a suggestion, given the possible consequences on sexual activity and couple life, I would suggest that spouses or partners also be involved in the decision.

Philippe Nicot, teaching general practitioner, University of Limoges

The original version of this article was published on The Conversation.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


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Myths in medicine, but does their rebuttal make it possible to install the facts in a lasting way?

Cécile Bour, MD, May 24, 2020

During the Covid-19 pandemic that we have just experienced, science based on facts has been severely mistreated... General panic, mediocrity of the media combined with incredible assurance of a single researcher sounded the death knell of the serene search for facts, proclaimed as miraculous a treatment without having the proof, stepped on the principle of primum non nocere, (first do no harm), which is the foundation of our medical practice.

Independently of fundamental questions, which is not our subject, we can see that the urgency of a health situation facilitates drifts, sloppy studies, but also statements made by personalities who are not aware of scientific constraints, but who want to impose their convictions.

The interesting question is: does even strong evidence that can bury doubts and polemics have the power to put an end to myths and beliefs that are deeply rooted in medicine?

And above all, will they be tolerated in a context of serious illnesses, where public is asking for hope and where  scientific community and public authorities prefer to persist in a benevolent ideology, however fallacious?

Parallel of the epidemic situation with the myths conveyed during screening campaigns

Being a group focused on issues of public medical information and interference of non-medical stakeholders in scientific controversies, as we regularly experience during pro-cancer screening campaigns, we can draw parallels with history of breast cancer screening, where economic stakes and beliefs have prevailed over reasoning.

The public does not like uncertainty, and the tremendous desire to overcome major health threats enables the appearance and immoderate expression of promises of salvation and healing.

How was it possible to impose the mantra that screening is a preventive act, and that regular mammograms can drastically reduce the risk of dying from this disease?

To understand, a bit of history

At the very beginning of the history of screening, between the 1970s and 1980s and in various cities, counties and countries (Norway, Denmark, Canada, New York, Swedish counties, Malmö in Sweden,) women were included in so-called trials, meaning studies that consisted of simply comparing the outcome of screened women against that of unscreened women.

At that time this could be done, as women had never received an X-ray of their breasts before; they were what can be called "pure cohorts". And these early comparative studies claimed a tremendous decrease in mortality through screening, up to 30% reduction in the risk of dying from breast cancer.

 Presented in this way, this performance seemed very pleasing. In view of these results, it seemed intuitively obvious that breast cancer screening would allow earlier diagnosis, earlier treatment and thus a drastic reduction in mortality by eradicating the most serious forms.

But science is sometimes a colossus with feet of clay, and while some erected convenient convictions, other researchers, more scrupulous and suspicious, drove the stings of doubt into this base of certainties.

Indeed, it became quickly clear, (this is no longer contested by the scientific community), that these first trials had many biases, such as irregularities in method, in distribution of women between the two groups and in statistical analyses. The methodology of trials did not meet current quality criteria. For example, some of women "screened" by mammography had tumors that were already clinically palpable! Even the published results of the so-called trial in the two Swedish counties were incompatible with the data in the Swedish national file. The best results had been obtained with the less good mammograms, none of the equipment used then would be approved for use today.

While victorious publications multiply between 1992 and 2000, along with an important media and social relay on women, physicians and governments, Gotsche and Olsen, two independent Nordic researchers, proceed, in 2000-2001, to a meta-analysis according to the methodology of the independent Cochrane collective to which they belong.

And then it's a shock.

(Meta-analysis is a scientific method of combining the results of a series of studies on a given problem according to a reproducible protocol, here: does screening reduce mortality from disease. It allows a more precise analysis of the data by increasing the number of cases studied in order to draw a general conclusion. By grouping together the previous trials carried out, data on 800,000 women were obtained).

Gotsche and Olsen quickly realized that none of conducted trials were of high quality and that they all had biases, sometimes significant. By combining the best trials (the so-called Malmö 1, and the Canada 1 and 2 trials), it appears that there is no statistically significant difference in mortality between screened and unscreened women. Obviously, this is a colossal turnaround while enthusiasm for this public health procedure, which was supposed to solve the cancer problem once and for all, was in full swing.

Unfortunately for the researchers, they did not get authorization to publish their results in Cochrane reviews, and the powerful Cochrane "breast cancer group" forced them to include even biased trials in order to improve the results; after long negotiations, and with inclusion of the poorest trials, the authors still found only a very meagre and hypothetical benefit. They added at the end of their publication that the best trials show no decrease in mortality, and that the indicator "mortality from breast cancer" is unreliable.

About these negotiations that took place, read here : Trouble in the world of evidence

But in the end, the press preferred to retain the beautiful story of a life-saving screening, as did savant societies, women largely influenced by a glowing press, doctors, health authorities....[1]

However, other meta-analyses, the American USPTTF* in 2000 and the French independent review Prescrire in 2006 corroborate these equally disappointing results, even with different age groups studied, different observation periods and different cohorts.

* U.S. Prevention Services Working Group of primary care and prevention experts who review evidence of effectiveness to develop recommendations in the area of prevention.

The conflicts of interest that have plagued the whole history of breast cancer screening are very well documented on the Formindep website [2] [3], and are reported in the very complete report of the citizens' consultation (starting on page 63).

Conclusion

Science applies a method of doubt to beliefs and superstitions, and to itself as well, in well-done studies.

Uncertainty in the face of health dangers encourages beliefs and reassuring hopes, all the more so as this uncertainty is strong, not only on the magnitude of the threat itself, but also on the means of countering it.

The first bearer of good news becomes a hero, a savior. Any reasonable protester who applies his method of doubt becomes a public enemy.

With the history of screening we see how myths and intuitive ideas, simple to understand but false, once established, have a long way to go.

For three decades now, the myth of "preventive" screening, "life-saving for women", has been firmly anchored in people's minds, regularly promoted by the public authorities, the National Cancer Institute and the health authorities, valorized by public personalities who are committed to its promotion. Evidence of its ineffectiveness and, worse, of its deleterious effects, is little mediatized, has no right to be quoted; those who want to evoke it and warn women are called conspirators, incompetents, evildoers for the cause of women and are inaudible during the pink October campaigns.

Current Covid-19 crisis has revealed the fragility of science in relation to belief, and has highlighted all the possible excesses once we move away from the search for facts, act in haste, and adhere to convictions justified solely by their comforting character.

References

1] All of this is documented in the report of the citizen and scientific consultation on screening in 2016, starting on page 51, see also https://cancer-rose.fr/wp-content/uploads/2019/07/depistage-cancer-sein-rapport-concertation-sept-2016.pdf.

As well as in Bernard Duperray book "Dépistage du cancer du sein, la grande illusion" published by Th Souccar, starting on page 26.

2] https://formindep.fr/les-cinquiemes-rencontres-du-formindep/

3] https://formindep.fr/?s=Tabar%2C+Lancet

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


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Overdiagnosis of thyroid cancer, another woman’s concern

June 5, 2020

Summary, Cécile Bour, MD

https://www.lequotidiendumedecin.fr/specialites/cancerologie/le-circ-sinquiete-du-surdiagnostic-du-cancer-de-la-thyroide

IARC concerned about overdiagnosis of thyroid cancer

Overdiagnosis is a real problem in our over-medicalized modern societies. It is becoming a vast public health issue, leading entire populations into the torments of disease that they would not have experienced without the unnecessary over-detection by all kinds of screening, of which so-called "preventive" medicine is so fond.

The physician and methodologist D. Sackett is very critical of preventive medicine, which he describes as follows:

  • Affirmative on healthy individuals without any symptoms, telling them what to do to stay healthy;
  •  Presumptuous, claiming that its interventions will generally do better rather than worse to those who adhere;
  • Tyrannical, doing everything possible to exert its authority through media campaigns based on public fears, and attacking its opponents.

Concerning thyroid cancer screening, which we will discuss below, the female population is once again paying the price of unrestrained over-medicalization, as for breast cancer.

Overdiagnosis of cancers

Overdiagnosis is the undesirable surprise-guest of mass population screening. Dr. B. Duperray has contributed enormously to a better knowledge of overdiagnosis in breast cancer screening.

Screening for prostate cancer, which is still prescribed, is no longer recommended by the health authorities because of serious damage to men's health. In an article of 2017, we discussed its overdiagnosis.

Things seem more nuanced for colon cancer screening, with a screening whose logic of promotion is moving from a screening for all , rather to a proposal for patients most at risk (with risk of colorectal cancer at 15 years ≥3%), this done with a fair information of the patient and a shared decision.
(Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta- analysis
Henriette C Jodal, Lise M Helsingen , Joseph C Anderson, Lyubov Lytvyn, Per Olav Vandvik, Louise Emilsson Jodal HC, et al. BMJ Open 2019;9:e032773. doi:10.1136/bmjopen-2019-032773)

Overdiagnosis of thyroid cancer

Overdiagnosis of thyroid cancer is a well-known phenomenon, already mentioned as early as 2016 [1] by the IARC [2] itself [3].

In a 2016 NEJM study, it was estimated that more than half a million patients were over-diagnosed between 1988 and 2007 in 12 high-income countries, with a dominant female population.

At the time, the IARC was already denouncing the high rise in the number of small papillary thyroid cancers (the most frequent and least dangerous form) and that, since 80-90s.

According to researchers, this alarming increase in the number of small papillary cancers, observed in France and in several developed countries (United States, South Korea, Italy, Japan), is above all the consequence of the growing use of increasingly precise imaging methods, in particular cervical ultrasound, and not the consequence of other factors sometimes cited such as the impact of nuclear accidents. According to researchers, up to 90% of thyroid cancers diagnosed in recent decades, mostly in women (84% in France), are most often overdiagnosed.

New IARC alert

 "Overdiagnosis of thyroid cancer is increasing rapidly around the world and has become a major public health challenge," warn researchers at the International Agency for Research on Cancer once again.

In collaboration with the Aviano National Cancer Institute in Italy, cancer registries in 26 countries on four continents were studied. Recently published in "The Lancet Diabetes & Endocrinology", the study found a very significant increase in thyroid cancer incidence (rate of new cases) between the periods 1998-2002 and 2008-2012 in all analyzed countries.

This overdiagnosis of thyroid cancer is more pronounced in middle-aged women (between 35 and 64 years old). The proportion of overdiagnosis from 2008-2012 varied around 40% in Thailand and over 90% in South Korea.

In France

In France, the overdiagnosis rate among women is estimated by the authors at 83%, which corresponds in gross figures to 25,000 patients between 2008 and 2012.

In all countries

More than 830,000 women and over 220,000 men may have been overdiagnosed between 2008 and 2012.

The origin of the problem

The origin of the problem should be sought in medicine itself, the authors point to the increased surveillance of the thyroid gland, in particular by cervical ultrasound, leading to the over-detection of many harmless tumors, that will be all treated once found.

 In South Korea, where the phenomenon was well monitored, overdiagnosis was the consequence of the thyroid examination routinely performed in screening programs.

 IARC Recommendation

IARC researchers urge governments to be vigilant and to review recommendations for screening asymptomatic patients.

Overdiagnosis leads to lifelong damage, overdiagnosed lesions are all treated with radical thyroid ablation and replacement therapy for the rest of the patient's life. The psychological consequences of the announcement of cancer are often dramatic and should not be underestimated.

A financial consideration is not insignificant: the costs generated by over-diagnosis divert countries' resources to other areas of care more appropriate to the health of the population.

Editor’s note

This problem is very well addressed by the science journalist John Horgan, in an article on what he names "the cancer industry", which we have shared.

References

[1] https://www.revmed.ch/RMS/2016/RMS-N-528/Surdiagnostic-de-cancer-de-la-thyroide-560-000-cas-en-vingt-ans

2] WHO International Agency for Research on Cancer, based in Lyon.

[3] https://www.vidal.fr/actualites/19934/cancer_de_la_thyroide_face_au_surdiagnostic_massif_et_ses_consequences_le_circ_appelle_a_la_prudence/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Blatant disregard for informed consent in screening

Summary by Cécile Bour, MD

September 18, 2020

BMJ: first published as 10.1136/bmj.m3592 on 17 September 2020.
Quote this as: BMJ 2020;370:m3592
Published: 17 September 2020
https://www.bmj.com/content/370/bmj.m3592

Hazel Thornton is a health science researcher at the University of Leicester.

She received her PhD in Science from the University of Leicester for her contributions to medicine and patient care. The award recognizes her work in advocating for patients and changing perceptions within the medical research and health care community.

The BMJ publishes her letter on the subject of patients' informed consent, which is often flouted, even though this is a right and a major ethical issue.

Hazel Thornton refers to a publication by Helen Haskell [1] [2], founder of Mothers Against Medical Errors, which reports the severe criticisms of the "Cumberlege Report" [3] on the British health care system, judged "disjointed, siloed, unresponsive, and defensive”.

The report points to the failure regarding the informed consent of healthy patients, whose non respect is a violation of human rights according to the Declaration of Helsinki [4].

What is of great concern is “the testimony from hundreds of patients reporting lack of informed consent.”

While health care professionals are supposed to work “in partnership with patients to make good clinical decisions," which is at “the heart of good medical practice".

Informed consent and screening

Hazel Thornton writes in her letter to the BMJ:

Asymptomatic people, too, are the target of health professionals in preventive medicine. Medical interventions used in screening are not without potential for harm, so properly informed consent must be sought. Not to do so is an abuse of human rights. Flouting the four basic principles of medical ethics—autonomy, beneficence, non-maleficence, and justice—must not go unchallenged. Incredibly, in the 21st century, blatant disregard for the right to proper consent is still occurring. Two examples clearly illustrate this.

The first is an experiment to determine the effects of manipulating invitation information provided to around 6000 asymptomatic women in the province of Messina, Sicily, “to increase uptake” into their breast cancer screening programme.[5] The second is the UK NHS breast screening programme AgeX trial, which was started in June 2009 and announced as “likely to be the largest randomised controlled trial ever undertaken in the world,” recruiting millions of women. Efforts to challenge this trial, with its flawed consent process, have met with “siloed, unresponsive and defensive” attitudes.[6] [7]

H.Haskell says, "How to change it is still an unsolved problem. There have been inquiries, reports, and recommendations over the years, but the fundamental issues around power, justice, and compassion are still with us. " What can be done to end these blatant abuses of the right to properly informed consent and tackle the lack of engagement ? 

Cancer Rose Reflections

Indeed, we have to draw a parallel with the European MyPEBS clinical trial on personalized breast cancer screening.

We have already reported its multiple shortcomings, which we denounced in a joint letter from 4 groups defending independence and integrity in health, a letter relayed among others in the BMJ.

Participants in this MyPEBS study are provided with a so-called consent brochure. The problem is that it does not comply with the law, which requires that this consent be based on fair, clear, complete and unbiased information.

We have summarized our concerns about the brochure for the MyPEPS study here (see point 3 ): https://cancer-rose.fr/my-pebs/2019/06/13/argument-english/

Over-treatment is not mentioned, with over-diagnosis indicated at its lowest range.

In conclusion, we have the same questions as Hazel Thornton:

After the French scientific and citizen consultation, which demands fair and complete information [8], how many laws, declarations, reports and investigations should we hope for in order to obtain the fundamental right to information and informed consent for the patient, and a firm and solid commitment from health authorities and governments to guarantee this right to the patient?

Références

References

[1] https://pubmed.ncbi.nlm.nih.gov/32763955/

[2] https://patientsafetymovement.org/advocacy/patients-and-families/patient-advocates/helen-haskell/Founder of Mothers Against Medical Error

[3] Haskell H. Cumberlege review exposes stubborn and dangerous flaws in healthcare. BMJ 2020;370:m3099.
doi: 10.1136/bmj.m3099 pmid: 32763955

[4] World Medical Association. Declaration of Helsinki. https://www.wma.net/fr/policies-post/declaration-dhelsinki-de-lamm-principes-ethiques-applicables-a-la-recherche-medicale-impliquant-des-etres-humains/

5] Italian study on the manipulation of women, we talk about it here :https://cancer-rose.fr/en/2020/12/17/manipulation-of-information/

[6] Bewley S, Blennerhassett M, Payne M. Cost of extending the NHS breast screening age range in England. BMJ 2019;365:l1293.
doi: 10.1136/bmj.l1293 pmid: 30971394

[7]We were talking about this trial

here : https://cancer-rose.fr/en/2020/12/29/cost-of-extending-the-nhs-breast-screening-age-range-in-england/ and here: https://cancer-rose.fr/en/2020/11/30/the-largest-clinical-trial-in-great-britain-on-breast-cancer-screening-was-halted/

[8] https://cancer-rose.fr/en/2020/12/30/citizen-and-scientific-consultation-on-breast-cancer-screening-in-france-steering-committee-report/

See at the end of the article the summary of the citizens' requests in red, first point being related to the quality of information

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


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High risk of breast cancer and mammography, in practice

JANUARY 18, 2021

(We have addressed this specific topic in two articles, below is a practical summary at the request of one of our readers. [i] [ii])

The first problem is to define a woman who is at high potential risk of developing breast cancer during her lifetime. And what is a "family at risk".
A family history alone, even a direct one, does not constitute the proof of being a person "at risk", contrary to what is often presented as a scarecrow to women.
We receive plenty of testimonials from young women who are unnecessarily alarmed and above all incited to unnecessary and dangerous over-medicalization.

What about the search for genetic mutations in women? When should it be done? 

This is the question that the independent French medical journal Prescrire addressed, Volume 36 N°388/February 2016.

Genetic mutations in the BCRA1 and BCRA2 genes are autosomal dominant, and women with these mutations are at higher but earlier risk of breast and ovarian cancer than the general population.

-The median age of onset is 40 years and the cumulative risk of cancer at age 70 is 51% to 75% for the BRCA1 mutation, 
-The median age is 43 years and the estimated cumulative risk is 33% to 55% for the BRCA2 mutation.

The journal Prescrire proposes the following criteria as significant backgrounds for proposing an onco-genetic consultation:

-Three people from the same branch, with breast cancer before the age of 70,

-Two people in the same branch, with cancer before the age of 50

-A person who has had ovarian cancer

-A person with breast cancer with a diagnosis before the age of 40, or a bilateral form, the first one before the age of 50, or a hormone receptor negative cancer that occurred before the age of 60.

Eisinger Score

The Eisinger score is a decision aid for requesting an onco-genetic consultation.(Click below to download) :

Several situations can arise in families with multiple cases of breast cancer:

A- Mutation identified in a woman in the family, presenting a breast cancer.

This search for genetic mutation brings valuable information to the women in the family: women who are carriers have a higher risk, women in the same family who do not have it, end up with the risk of the general population.

If a woman in the family decides to do a mutation search on the BCRA1 or BCRA2 genes because of a loaded genealogy, and finds herself carrying a deleterious mutation on these genes, then her risk of developing breast cancer appears to be high, and this risk is also very high for relatives.

B- No mutation found in women with breast cancer.

Either there is really no mutation and the patient has developed a form of cancer without a genetic cause, or there is a mutation, but it may be due to an unidentified genetic cause.

Therefore, there will be uncertainty for the women in her family regarding the hereditary nature or not of this cancer, the risk of the familial nature of this cancer is not as high as in the case of an identified mutation such as BRCA but probably slightly higher than in the general population.

Uncertainty makes it necessary to analyze genealogy, which also has its share of uncertainties and imprecisions…

C- The person with breast cancer has not done any genetic research.

For the women among the relatives, this gives useless information: either the ill person may have had a mutation that was not researched, or she is free of a mutation but the mutation possibly exists in the family members.

All overall, the following points should be kept in mind:

  • Either the person presents a family case carrying a mutation but she is free of any mutation herself, her risk will be close to that of the general population. 
  • Or the person has the mutation and can be estimated to have a higher risk of breast cancer than the general population.
  • But for other women there are still uncertainties about their family's risk of breast cancer:

-In women whose family members have had breast cancer but without a mutation found in only one of the family cases,
-In women with a personal genetic research of a mutation that is negative, with a genealogy presenting several cases of breast cancer, but without research done on the ill persons.

Proposals of conduct to be followed, different options depending on the situation

Who are the individuals with the highest theoretical risk?

-Woman with a case of breast cancer in a first-degree relative (mother, sister, daughter) before the age of 40.

-Two women with breast cancer in the family of first or second degree.

-Male relative with breast cancer in the family of the first or second degree

-First or second degree female relative with ovarian cancer.

Summary according to the Prescrire dossier published in the Revue Prescrire May 2016/Tome 36 N°391-p.355 to p.361

Here is a table summarizing the proposed courses of action according to the presence of mutation or not, and proposals for complementary imaging (downloadable table, click below):

TABLE

EXISTING RECOMMENDATIONS IN FRANCE

1°In 2014, the French National Authority for Health (Haute Autorité de Santé) issued recommendations that are still in force:

https://www.has-sante.fr/upload/docs/application/pdf/2014-05/depistage_du_cancer_du_sein_chez_les_femmes_a_haut_risque_synthese_vf.pdf

2° The recommendations of the National Cancer Institute, click (table p.10 of the doc)

As you will read, early and annual mammography is recommended, ignoring the greater risk of radiation-induced cancer, which can occur, depending on mutations, as early as the first mammogram. iii] [iv]

For these women at particular risk, recommendations are made without any objective data on the impact of different screening strategies, on overall mortality data, breast cancer mortality, mastectomies, treatment effects, over-diagnosis and false alarms for this at-risk population. In absence of data, these women and their caregivers are unsure of what to do and are struggling empirically.

While assessments are conducted on the general population, it is equally important to do them in these special populations, but they are not available.

General cautions

A thorough discussion should be undertaken with the patient because the knowledge of this high risk will condition for her, in addition to an important psychological burden:

-Permanent anxiety

-Numerous false alarms (false positives)

-Over-diagnosis is highly probable but not evaluated since no studies have been carried out to quantify it.

To quote the May 2016 issue of the journal Prescrire: "To ensure that screening has a favorable benefit-risk balance, it is not enough to determine the most effective detection method: earlier diagnosis does not always change the burden of treatment for patients, nor necessarily the prognosis of the disease".

"It is also necessary to establish the conditions where this translates into tangible clinical benefits for the people screened. It is also important to measure the undesirable effects to which all screening exposes people: over-diagnosis and over-treatment, sources of serious undesirable effects sometimes; iatrogenicity of the tests; false positives causing anxiety and useless tests; medicalization of the healthy person's existence. »

And further on, on the ethical aspect:

"Ethics. The magnitude of the risk of breast cancer in these higher-risk women compared to the general population does not make it unethical to conduct randomized clinical trials, on the contrary. Clinical trials comparing the effects of various screening strategies on clinical criteria such as total mortality, breast cancer specific mortality, frequency of breast amputations, frequency of cytotoxic treatments, would provide the answers that are lacking, instead of leaving women and caregivers without solid evidence for these important decisions". 

According to the journal Prescrire, a U.S. evaluation reports 125 cases of radiation-induced breast cancer per 100,000 women between 40 and 74 years of age screened by mammography every year, 16 of which are fatal. And for high-risk women, it has been shown that breast cancer was twice as frequent in women exposed to x-ray examinations before the age of 30 than in those not exposed.

Other complementary exams

Other exams than mammography, each having its limits, and an adapted follow-up can be proposed.


MRI

This exam has a higher sensitivity compared to mammography and is less radiating.

MRI + Mammography:
84% of cancers found

MRI alone:
75% of cancers found

Mammography alone:
32% of cancers found

These proportions are almost identical for women at high risk, but here the problem is the same, we do not know the proportion of overdiagnosis. It is not known whether there is a gain in survival for these women who are followed in this way, or whether, on the contrary, they are exposed to more overdiagnosis and invasive treatments.

The long-term effects of Gadolinium injected annually are also unknown. The assessment of this potential risk is all the more necessary as these women will be integrated into heavy surveillance protocols, with multiple repeated MRI scans.

This product has possible side effects during injection and some cases of allergic reactions have been described.

Ultrasound:


this examination increases overdiagnosis and exposes to false positives and multiplies unnecessary biopsies.

Clinical examination by a professional:


The authors of the Prescrire dossier did not find any study evaluating the performance of breast self-examination.

But according to all the studies examined by the authors, it seems that at least half of the cancers discovered by an imaging examination were not diagnosed by the clinical examination carried out at the same time. It is not known if a delay in clinical diagnosis would be life threatening, as this has not been evaluated.

References

[i] https://cancer-rose.fr/2016/11/20/observations-femmes-a-risques/

[ii] https://cancer-rose.fr/2016/11/20/depistage-et-risque-familial-eleve-de-cancer-du-sein/

[iii] https://cancer-rose.fr/en/2020/12/15/radiotoxicity-and-breast-cancer-screening-caution-caution-caution/

[iv] https://its.aviesan.fr/getlibrarypublicfile.php/cd704e89988a4e3bcf2e1217566876cf/inserm/_/collection_library/201800012/0001/J1-098ITS-2017.foray.lyon.ITMO.TS..21.nov.2017.pdf.pdf

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Additional MRI screening for women with extremely dense breast tissue

https://www.nejm.org/doi/full/10.1056/NEJMoa1903986
Bakker, M. F.; de Lange, S. V.; Pijnappel, R. M.; Mann, R. M.; Peeters, P. H. M. and all, Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381(22):2091–2102 , DOI: 10.1056/NEJMoa1903986

Synthesis Cécile Bour November 28, 2019

Background

Extremely dense breast tissue is believed to be a risk factor for breast cancer, a factor that is especially limiting for cancer detection by mammography.

The aim is to test whether the use of MRI would reduce the occurrence of interval cancers, i.e. cancers appearing between two mammograms, the previous mammogram having been considered normal.

Method

This is a randomized controlled trial (study subjects randomly assigned to either group), multicentre (conducted in two or more centers with the same protocol and a coordinator responsible for processing all data and analyzing the results).

It is carried out by van Gils and his colleagues in the "DENSE" trial group.

The researchers divided 40,373 women between 50 and 75 years of age with extremely dense breast tissue and negative screening mammogram results, into two groups: either the "additional MRI" group or the "screening mammogram only" group; specifically 8,061 women in the "MRI-invitation" group and 32,312 women in the "mammogram-only" group.

A control mammogram was then performed after two years for both groups to compare the results in terms of the number of cancers found.

The main finding was the difference between the groups in the incidence of interval cancers over a two-year screening period.

The researchers stated that “Such patients may benefit from a tailored breast-screening strategy, supplemented with more sensitive imaging methods. The benefit of supplemental imaging is the subject of a worldwide debate. In the United States, a federal law directs breast-density reporting,but supplemental screening is not recommended in American guidelines. “

Although complementary imaging increases the rate of cancer detection in women with dense breasts, the question that remains is whether it improves health outcomes. Read about it: https://jamanetwork.com/journals/jama/article-abstract/2733521

Conclusion of the study

Additional MRI screening appears to be associated with fewer interval cancers compared to mammography alone in women with extremely dense breast tissue and normal mammography results. It appears that for dense breasts, the risk of interval cancers is reduced by half in women with negative mammograms and MRI screening.

Specifically, the researchers found that the interval cancer rate was 2.5 per 1,000 screenings in 4,783 women in the MRI-invitation group compared to 5 per 1,324 women in the mammography-only group.

Overall, 59% of women in the MRI group really attended this additional screening. Of the 20 interval cancers diagnosed in the group that was invited for MRI, 4 were diagnosed for women receiving MRI, and 16 were diagnosed for those who did not receive MRI.

Limitations of the study

  • False positives : Supplemental MRI scans were associated with a cancer detection rate of 16.5 per 1,000 screens and resulted in a false positive rate of 8.0% (79.8 per 1,000 screens). Among women who had a breast biopsy based on an MRI indication, 26.3% had breast cancer and 73.7% did not.
  • Sample not large enough.  To examine the effect of MRI screening on breast cancer specific mortality or overall mortality, the study would require a larger sample size and a longer observation period.

The lower rate of interval cancers observed in MRI participants may have an effect on mortality, but it would also be necessary to see a reduction in the number of advanced cancers in order to demonstrate a benefit on mortality reduction, which has not yet been demonstrated for mammography screening alone.

Reservations expressed 

In an accompanying editorial, Dan L. Longo, Associate Editor of the New England Journal of Medicine, and Professor. of Medicine at Harvard Medical School, (Boston), praised the high quality data from this unprecedented randomized trial: « It appears to show that among women with dense breasts, the risk of interval cancers is halved by following a negative mammogram with MRI screening ».

But the problem of over-diagnosis and the usefulness of additional screening in asymptomatic women, in whom lesions will be detected and be treated, without any evidence of survival or reduction in mortality, continues to be raised.

Dan Longo writes :

« But is a reduction in interval cancers an appropriate surrogate for improved overall survival? It appears that most of the cancers that were detected on supplemental MRI screening were found at an early stage. Ductal carcinoma in situ was 10 times more frequent among patients undergoing MRI, and these diagnoses were likely to lead to treatments. What remains unclear is whether the tumors would never otherwise have been detected or threatened the patient’s survival. »

« The ultimate test of the value of MRI screening in women with extremely dense breast tissue will be whether its use improves survival — an answer that we will not have for a very long time. In the meantime, we now have a trial showing that MRI screening can lead to a lower rate of interval cancers. The cost is that 74% of the biopsies that are subsequently performed will not lead to a cancer diagnosis, and we do not know whether the cancers that were detected needed to be found or treated. »

« So the dilemma remains. Women with dense breasts and a negative mammogram who undergo MRI have a very low risk of having breast cancer (16.5 per 1000 screenings in this trial) and an increased risk of a false positive scan. The findings of this trial are likely to reinforce the idea that MRI screening is important in women with dense breast tissue. But will we be putting these women at increased risk of procedures without contributing to their eventual survival? »

In addition, another study :

The concern about additional MRI screening is addressed in another controlled study of MRI screening for contralateral breast cancer patients in the United States. (Wang SY, Long JB, Killelea BK, et al. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with breast cancer. J Clin Oncol 2016;34:321-8.)

Although the incidence of invasive breast cancer in the contralateral breast after the screening period was lower with MRI screening than without screening, the overall incidence of breast cancer in the MRI group was twice as high as in the no MRI group, with no change in the incidence of advanced cancer throughout the five-year follow-up period. However, it is the incidence of advanced breast cancer that tells us whether or not screening is effective.

The researchers concluded :

“An increased synchronous contralateral breast cancer detection rate, attributable to MRI, was not offset by a decrease of subsequent contralateral breast cancer occurrence among older women with early-stage breast cancer, suggesting that preoperative MRI in women with breast cancer may lead to overdiagnosis.”

References

Bakker, M. F.; de Lange, S. V.; Pijnappel, R. M.; Mann, R. M.; Peeters, P. H. M. and all, Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381(22):2091–2102 , DOI: 10.1056/NEJMoa1903986

Longo, D.L, Detecting Breast Cancer in Women with Dense Breasts-Editorial, N Engl J Med 2019; 381:2169-2170 DOI: 10.1056/NEJMe1912943

Wang SY, Long JB, Killelea BK, et al. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurence among older women with breast cancer. J Clin Oncol 2016;34:321-8.

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Digital mammography not more effective in reducing the most serious cancers, according to Australian meta-analysis

by Cécile Bour, MD, June 28, 2020

https://academic.oup.com/jnci/article/doi/10.1093/jnci/djaa080/5859630

This is a meta-analysis of 24 studies of more than 16 million screening mammograms (10,968,843 film and 5,614,900 digital mammograms) by Australian researchers, which reported the following results :

With digital mammography is observed :

  • A statistically significant increase in recalls and false positives; bearing in mind that false positives can generate considerable anxiety in women who are misidentified as having breast cancer. After the transition to digital mammography, which began around the year 2000, a recall increase rate of 6.96 per 1,000 screens was  reported.
  •  No impact on the rates of interval cancers, these cancers not being anticipated by screening because they are often very rapid and progressive and appear between two screening mammograms, despite a previous negative mammogram. Their rate is not lowered by digital technology.
  •  A modest but statistically significant increase in the cancer detection rate, however this improved detection rate is largely due to a higher detection of carcinoma in situ, the great majority of which are of unnecessary detection, with little difference in the detection of invasive cancers.

 Precisions and some reminders

1° Transition from analog to digital

Initially, mammography was analogical, i.e. using films that had to be developed. The radiological signal, to make it simple, is  transformed into a 'visual' signal, which involves technical uncertainties that can alter the quality of the film to be interpreted (film artifacts, quality and fragility of the films, problems with developing baths, etc.). With the digital process, used in screening since 2008, sensors retrieve the image, store it in memory, there is no transformation of the signal and the image is projected in real time on the computer screen (or console). The diffusion of the signal is limited to the maximum ('photon counting' technique) to keep only the useful information. This technology has been acclaimed for its better detection rate compared to the analog system, especially in case of dense breasts, and for its lower irradiation.

This last aspect is certainly not negligible, but should be relativized, since radio-biologists have made us understand the mechanisms of radio-toxicity, which is much less dose-dependent than subject-dependent. See: https://cancer-rose.fr/en/2020/12/15/radiotoxicity-and-breast-cancer-screening-caution-caution-caution/

2° The impact of digital in terms of benefits

 In 2010, questions were already being raised about the real impact for women in terms of mortality reduction, because the interest of screening is to detect the cancers that endanger the most women's lives, and thus reduce mortality, a fact that is difficult to prove with breast cancer screening (reduction in breast cancer mortality since the 1990s, thanks to therapeutic advances, a reduction well before the advent of screening campaigns).

However, an increase in detection rate ranging from 20 to 28% with the digital technique (in fact according to the Australian study, there is 25% more detection for carcinoma in situ and only 4% more for invasive carcinoma), this represents only one additional cancer detected thanks to this new technique per 1000 women, and it does not mean that one more life is saved.

Screening performance is measured by mortality and not by the detection rate. The problem is that it preferentially detects a cancer that will be little or not life-threatening, and that would have been detected by analog mammography one year later anyway, or even in the absence of any screening by the appearance of a clinical symptom, without changing the therapeutic result. More cancers that would never have manifested themselves are also detected. The problem of overdetection by preferential detection of cancers with little or no evolution thus causing overdiagnosis, has already been raised.

3° The problem of over-detection of carcinoma in situ (CIS)

Below is a reminder of what we explained about in situ carcinoma of the breast: https://cancer-rose.fr/en/2020/12/30/a-blog-for-women-with-dcis-ductal-carcinoma-in-situ/

In situ carcinoma of the breast is defined by the proliferation of cancer cells within a galactophoric duct without the cells protruding beyond the wall of the duct to invade the rest of the breast.

It is essentially a mammographic finding, as 90% of women diagnosed with DCIS had microcalcifications on mammography.

The vast majority of these lesions do not threaten women's lives if they are not detected, their prognosis is very good, the 10-year survival rate, a parameter widely used by health authorities, is over 95%. There is the ductal form and the lobular form considered rather as a risk factor for breast cancer.

CIS contributes to overdiagnosis. Tests and studies show that the increasing detection of CISs has not contributed to the reduction of breast cancer mortality. Before the introduction of screening, CIS accounted for less than 5% of all breast cancers, rising to 15-20% in all countries where screening campaigns exist. They are not counted in the incidence figures (rate of new cases) given by the National Cancer Institute, as they are considered separately and not as "true" cancers.

In addition, there is a lack of real consensus among pathologists for the classification of these lesions in the analysis of the biopsies they receive, with a tendency to outclass them in poorer prognostic categories, for fear of underestimating a "disease".

Most CIS are considered as non-mandatory precursor lesions to invasive cancer; paradoxically, the dramatic increase in their detection followed by their surgical ablation has not been followed by proportional decreases in the incidence of invasive cancers.

The major problem is that these particular breast cancer entities are treated with the same severity as breast cancer.

In November 2016, a study carried out by University of Toronto reported  the following results:

- Their treatment makes no difference in women's survival.
- Women with CIS are heavily treated (sometimes by bilateral mastectomy) and have the same likelihood of dying from breast cancer as women in the general population.
- Treating CIS does not decrease their recurrence.
- Preventing recurrence by radiation therapy or mastectomy would also not reduce the risk of mortality from breast cancer.

Similarly, our study of mastectomies in France showed a steady increase in surgical procedures, our first hypothesis being the overtreatment of lesions that are not invasive cancers, but so-called pre-cancerous lesions and CIS [3] [4].

The long-term consequences of overtreatment can be life-threatening. For example, radiation therapy on these lesions appears to be unable to reduce the risk of death from breast cancer, but is associated with a dose-dependent increase (10-100% over 20 years) in the rate of major coronary events. [5]

In several countries, clinical trials are being conducted to test a simple active surveillance, especially for low-grade CIS, rather than aggressive treatment:

- COMET(US)
- LORIS(UK)
- LORD(EU)

For Philippe Autier [6], from the International Prevention Research Institute (IPRI), the problem is undoubtedly inherent to routine mammography, in particular digital mammography, which is too efficient for the detection of small calcifications; these are the most frequent radiological sign of these forms, and mammogaphy has an excellent sensitivity for the detection of these microcalcifications.

You will find in our media library several clinical cases of carcinomas in situ, abusively called carcinomas.

Conclusion of authors of Australian meta-analysis

The increase in cancer detection after the switch to digital mammography did not result in a reduction in interval cancer rates. Recall rates were increased.

These results suggest that the transition from film to digital mammography, primarily motivated by reasons of better technological performance, did not result in health benefits for screened women.

This analysis reinforces the need to carefully evaluate the effects of future technological changes, such as tomosynthesis [1] [2], to ensure that the new technologies lead to better health outcomes, beyond the gains in technical performance alone.

[1] Read : https://cancer-rose.fr/2019/11/28/avis-de-la-haute-autorite-de-sante-sur-la-performance-de-la-mammographie-par-tomosynthese-dans-le-depistage-organise/[2] Read also  : https://cancer-rose.fr/2019/03/09/association-de-la-tomosynthese-versus-mammographie-numerique-dans-la-detection-des-cancers/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Overscreening of older adults

August 4, 2020,
Summary, Cécile Bour, MD

Judith Garber, political scientist at the Lown Institute [1] had already published an interesting article on the opportunity to reduce screening during the Covid period and during lockdown [2].

This time she synthesizes in a publication of the Lown Institute the result of a study published in Jama on overscreening of older adults.

Background

In very old age, people are less likely to live long enough to benefit from the advantages of screening, but they are much more exposed to the risks of treatments that will follow the discovery of a lesion that would not have had the time to endanger their lives if it had not been detected. This is why the recommendations, whether American or European, set age limits beyond which screening will not only be useless but potentially harmful.

Judith Garber reminds us the figures of excessive screening in elderly people in a study conducted in 2014 among older patients at very high risk of mortality: 37.5% were screened for breast cancer, 30% were screened for cervical cancer and 40% were screened for colorectal cancer.

The study is published in the JAMA by researchers at the Penn State College of Medicine

Researchers analyzed the data set of more than 175,000 participants and measured the proportion of adults above the recommended age who reported being screened for colorectal cancer (age cutoff of 75 years), cervical cancer screening (age cutoff of 65 years) and breast cancer mammography screening (age cutoff 74 years). 

The results are as follows:

  •  45% of survey respondents reported having had a colorectal, cervical or breast cancer screening, even though they had exceeded the recommended age for screening set by the USPSTF [3]. 
  • Overscreening was most common for breast cancer, with 74% of women over 74 years of age having had a mammogram. 
  • Cervical cancer had the lowest rate of overscreening, with 45.8% of women over 65 years of age,
  • Yet 32% of women being overscreened despite a previous hysterectomy. 
  • Even people with a high mortality risk were no less screened than those with a longer life expectancy.

For breast cancer, there were disparities: women living in metropolitan areas, with good quality health care and in good or excellent health, were more frequently overscreened than women living in rural areas, without an usual source of care and poorer reported health status. (Editor's note: it should be noted that this fact was also reported in a previous study in the state of Sao Paulo in Brazil. [4] )

Higher levels of education were associated with higher rates of overscreening among women.

What are the reasons for overscreening of older adults and outside of recommendations?

According to the authors of the Penn State College of Medicine study, overscreening for women may be related to residing in urban areas, because women have easier access to screening facilities than women living in rural areas, and are offered more screening, whether or not it is appropriate.

Another hypothesis is that clinicians in rural areas have longer and more trusting relationships with patients, so that they have time to explain to patients why screening is no longer recommended after a certain age. 

Judith Garber brings up the interesting theory, which the authors did not raise, that the greater availability of medical facilities in cities, the fact that there are more technological offerings and more competition for patients in urban areas, encourage overuse of the system by medical insurance beneficiaries, and thus unnecessary screening, as a March 2020 study also suggests.

Researchers at the Penn State College Institute are calling for additional research on causes to reduce this persistent trend.

References

1] The Lown Institute (USA Massachusetts) is a non-profit organization, “a think tank generating bold ideas for a just and caring system for health“

[2] https://cancer-rose.fr/en/2020/12/15/reduction-in-the-number-of-cancer-screenings-during-the-covid-19-period-what-are-the-expected-consequences/

3] an independent U.S. organization of primary care and prevention experts that systematically reviews evidence of effectiveness and develops recommendations. 

4] https://bmjopen.bmj.com/content/7/8/e016395

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.