A letter from Ameli (French Health Insurance)

27 October 2022, by Cancer Rose

Dear Sir or Madam,

Your attending physician plays a central role in prevention actions. Depending on your situation, he can inform you and answer your questions about organized screening for breast, cervical and colorectal cancer, which can save lives. The earlier these cancers are detected, the better the prognosis.
To help your doctor in his mission of providing health advice to his patients, the Health Insurance will provide him with the list of his patients concerned by these screenings and who have not completed them (1).
Under the provisions relating to personal data protection, you have until December 1, inclusive, to oppose this transmission via the following link: https://www.demarches-simplifiees.fr/commencer/declarer-mon-opposition.
If you make your objection after December 1st, your request will not be considered for the first available list but will be considered for future lists.
Your situation could mean that some of these organized screenings do not apply to you; in this case, please disregard this message.

Please be assured of our attention and availability,
Your Health Insurance Correspondent

This is the letter that everyone has received from their Health Insurance.

Remember that during the citizens' consultation, the Health Insurance Institution's simplistic communication was criticized; read pages 95 and 96 of the citizen consultation on breast cancer screening report.
It cannot be stated that communication is more advanced in 2022, leaving any opportunity for reflection or doubt.

In this email, it is claimed that these screenings save lives. However, there is no scientific evidence, no study given, no justification, and no single reference. The message notifies you that your attending physician will be informed of the screenings you have not yet completed...
Ideally, one would hope that this approach would encourage discussion with the family physician about the relevance of screening, leading to a consultation that would result in a shared decision and information that would allow an informed choice. But what about in real life? One of our readers correctly asks if this will not instead allow putting a little more pressure on patients to participate in screenings that are losing momentum rather than an informed decision consultation if the health insurance institution itself starts with the presumption that screenings save lives, which is far from reality. There is little communication about the scientific challenges still rising regarding the true relevance of screening and its harms. [1] [2] [3] [4] [5].

The user who receives this email must activate the rejection; hence, if he does not click on the link allowing him to oppose, his acceptance is activated by default.

This initiative appears to be a part of the larger European plan to increase European population participation in various screenings, despite many scientists' requests for better information on the benefit-risk balance of these health programmes.
The target is for 90% of EU citizens to participate in colorectal, breast, prostate, and cervical cancer screenings by 2025.

The new French 10-year plan states (https://www.e-cancer.fr/Institut-national-du-cancer/Strategie-de-lutte-contre-les-cancers-en-France/La-strategie-decennale-de-lutte-contre-les-cancers-2021-2030):

“Improving access to screening will be strengthened.”

"It will be a matter of better understanding the determinants of reluctance to screening and simplifying access to screening (direct order, diversified health professionals, mobile teams in particular). Approaches will be developed that offer screening after a preventive intervention or unscheduled care.

For example, partnerships with food aid organizations will be considered to carry out awareness-raising efforts, particularly among the most disadvantaged. First, contact information tools for health, medical, and social workers will be provided, and mobile applications with information and reminders will be developed. To encourage people to participate in screening, material incentives will be tested. Finally, screening age limits will be reconsidered. "

The financial incentives specified in the text allow for the recruitment of the most economically disadvantaged people, again disregarding any medical knowledge, as was denounced in an article in the BMJ, whose one of its authors is a French citizen[6]. For these more vulnerable persons, the consequences of abusive screening can be dramatic, resulting in impoverishment, loss of income, and difficulty getting jobs.
The problem of these underprivileged people is much more the access to care than finding unnecessary cancers that would never have harmed them. It is also a problem of good medical information and fight against risk factors to which they are more exposed.

But sometimes, too much is the enemy of the good. With the other screenings of the European plan that are going to be added with new invitations, reminder letters, mobile applications, and increased medical consultations, the effect obtained could be the opposite: a weariness of the population, already more and more distrustful of medical injunctions, and who will turn away, as it is already the case, from traditional medicine that is more and more coercive and harassing.

Enough is enough.


[1] https://cancer-rose.fr/en/2022/09/13/the-risks-of-screening-an-elephant-in-the-room/

[2] https://cancer-rose.fr/en/2021/02/11/parallel-to-breast-screening-prostate-screening-overdiagnosis-as-well/

[3] https://www.nejm.org/doi/full/10.1056/NEJMoa2208375

[4] https://cancer-rose.fr/en/2021/02/01/overdiagnosis-of-thyroid-cancer-another-womans-concern/

[5] https://cancer-rose.fr/en/2021/02/24/being-a-woman-and-smoking-x-rays-in-perspective/

[6] https://www.bmj.com/content/376/bmj-2021-065726

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.

The short news of October 2022

Synthesis Dr C.Bour, October 20, 2022

1°-We start with an article in Medscape, written by Ryan Syrek,

editorial director of Medscape US, on sexual dysfunction and poor self-image in women treated for breast cancer, often with hormone therapy.

This is an almost taboo subject and is obviously under-addressed. The author's concern is the hype surrounding certain therapies with dubious or non-existent benefits. He also points to overtreatment in women with CCIS (carcinoma in situ) who "are generally uninformed about their diagnosis and make uninformed treatment decisions."

The insufficient information of healthy women (in relation to screening) as well as of affected women (on their therapeutic possibilities), can be once again to be deplored.

But what are the obstacles to informing women properly; laziness? Lack of time? Or is it also a persistent patriarchal consideration that women are insufficiently armed to understand or decide, and that they must be spared any cognitive overload? Is this a caricature? Not at all, the art of manipulating women has even given rise to a real study: https://cancer-rose.fr/en/2020/12/17/manipulation-of-information/

We would also like to add that information should already be focused on the risks of screening in general, and in particular on over-diagnosis, which is largely fuelled by the discovery of many "in situ" carcinomas (see FAQ article), the vast majority of which do not affect women, but which are unfortunately mostly detected by repeated mammograms.

2°-In the BMJ, the authors ask the question about doctors' knowledge of overdiagnosis, which should be a prerequisite for explaining it to patients.... A study is in progress, presented here: https://bmjopen.bmj.com/content/12/10/e054267.info

Piessens V, Heytens S, Van Den Bruel A, et al : "Do doctors and other healthcare professionals know overdiagnosis in screening and how are they dealing with it? A protocol for a mixed methods systematic review"  BMJ Open 2022;12:e054267. doi:10.1136/bmjopen-2021-054267

Introduction Overdiagnosis is the diagnosis of a disease that would never have caused any symptom or problem. It is a harmful side effect of screening and may lead to unnecessary treatment, costs and emotional drawbacks. Doctors and other healthcare professionals (HCPs) have the opportunity to mitigate these consequences, not only by informing their patients or the public but also by adjusting screening methods or even by refraining from screening. However, it is unclear to what extent HCPs are fully aware of overdiagnosis and whether it affects their screening decisions. With this systematic review, we aim to synthesise all available research about what HCPs know and think about overdiagnosis, how it affects their position on screening policy and whether they think patients and the public should be informed about it.

Methods and analysis We will systematically search several databases (MEDLINE, Embase, Web of Science, Scopus, CINAHL and PsycArticles) for studies that directly examine HCPs' knowledge and subjective perceptions of overdiagnosis due to health screening, both qualitatively and quantitatively. We will optimise our search by scanning reference and citation lists, contacting experts in the field and hand searching abstracts from the annual conference on 'Preventing Overdiagnosis'.

After selection and quality appraisal, we will analyse qualitative and quantitative findings separately in a segregated design for mixed-method reviews. The data will be examined and presented descriptively. If the retrieved studies allow it, we will review them from a constructivist perspective through a critical interpretive synthesis.

3°-In the Annals of Internal Medicine is presented an initiative that our French National Cancer Institute could learn from. https://www.acpjournals.org/doi/10.7326/M22-1139

For the authors, Aruna Kamineni, V. Paul Doria-Rose, Jessica Chubak, et al, cancer screening should be recommended only when the balance of benefits and risks is favorable. The review presented here evaluates how US cancer screening guidelines report risks.

Objective: To describe current reporting practices and identify opportunities for improvement.
Design: Guideline review.
Setting:United States, study funded by the American Cancer Institute.
Patients: Patients eligible for breast, cervical, colorectal, lung, or prostate cancer screening according to US guidelines.
Results: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type.

The review identified opportunities for improving conceptualization, assessment, and reporting of screening process–related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery.

4°-Finally, two more publications:

A "letter to the editor" by Rani Marx (Medical Decision MakingVolume 42, Issue 8, November 2022, Pages 1041-1044)and a recent editorial, by Marilyn M. Schapira, Professor of Medicine in Pennsylvania and Katharine A. Rendle, Assistant Professor of Family Medicine and Community Health at the Perelman School of Medicine (Pennsylvania), both advocating for awareness of the need for de-escalation of screening and the need for change for the benefit of women.

In her letter "Overscreening for Women's Cancer: Time for Change," Dr. Marx, an epidemiologist and patient, relates:
"Unnecessary and potentially dangerous cancer screening for women is a burden on health care and likely harms patients." The author decries "abundant testing, despite little evidence of improved population health or reduced mortality..."
Furthermore, she shares her own experience in 2020.

In her commentary "Overscreening for Women's Cancer: Time for Change," Dr. Rani Marx addresses the complex issue of informed, value-based decision-making in women's health. Drawing on her experience in health services research and epidemiology, as well as her own experience as a 'patient', Dr. Marx describes her frustrating attempts over a lifetime of screening to engage clinicians in considering the importance of risk on benefit-risk balance. She exposes the trade-offs involved in making decisions about cancer screening tests.
When asked, Dr. Marx explains, many patients and clinicians accept and recognize the need to de-escalate care when supported by scientific evidence, and to engage in an informed, shared decision-making process.

The editorial by Schapira and Rendle, on the other hand, advocates for the challenge of de-escalation: a multi-level change is needed to improve clinical practice. These improvements should focus on guidelines, efforts to achieve consensus on those guidelines, and shared decision-making processes between a woman and her clinician, leading to individualized screening decisions that reflect the woman's values and preferences.

This is in fact what the citizens' consultation demanded, but the road is long, and shared decision making appears to be a mirage when we see the INCa's television spots encouraging women to undergo screening, or the institute's information documents, which are still insufficiently balanced and scarcely descriptive of the risks of screening.

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.

The new INCa 2022 booklet on breast cancer screening

October the 20th

In 2017, we conducted a critical review of the French National Cancer Institute (INCa) information booklet for women on breast cancer screening, being sent with their first invitation.

At the time, the score for the quality of the information was not outstanding. A new 2022 edition for women is now accessible online. We will examine and compare the changes made between the two editions.

Sophie, our patient referent, compared the two booklets to assess how the INCa's communication was progressing. Below is a summary of the analysis she conducted.

The negative points 

1) This booklet is only sent once, at the age of 50, for the first screening, and then at each of the subsequent screenings, a different document (a short leaflet) is provided: the leaflet does not mention any of the harms of screening. Instead, it indicates a link to a website for more information. It is obvious that, over time, the message that will remain in the minds of women will be the one in the leaflet, with none of the harms presented, which will be completely forgotten.

2) Among the benefits, a special emphasis is placed on 5-year survival, which is not an indicator for screening effectiveness.

3) The mortality reduction is presented as a relative percentage reduction (15-21%), meanwhile the overdiagnosis is presented as an absolute percentage (10-20%), which are not comparable. This flaw exists in the 2017 booklet as well.

ATTENTION: A 20% decrease in cancer mortality does not mean that 20 fewer women screened out of 100 will die of cancer. This is just an indication of relative risk. The authors disregard the request of women citizens to no longer be misled by numbers that do not mean what they appear to suggest. The 20% fewer deaths does not mean that 20 fewer women out of 100 will die of breast cancer if they are screened. The 20% reduction in deaths is only a relative risk reduction between two compared groups of women.

In fact, according to a projection made by the Cochrane Collaboration based on several studies, for every 2,000 women screened over a period of 10 years, 4 will die of breast cancer; for a group of women not screened over the same period of time, 5 will die of breast cancer; the reduction from 5 to 4 mathematically represents a 20% reduction in mortality, but in absolute terms, only one woman's death will be prevented.

Actually, this corresponds to an absolute risk reduction of 0.05% (1 woman in 2000) to 0.1% (1 woman in 1000) at the end of 10 to 25 years of screening, depending on the estimates used (American, US TaskForce, Prescrire journal). (5)

Concerning the rate of overdiagnosis, the 10 to 20% indicated corresponds to the lowest evaluation, other studies suggest much higher rates of overdiagnosis.

4) The NIH (National Cancer Institute) website is cited in the booklet's references to support the survival statistics put forward in the booklet. But it omits the page of the same institute that indicates that survival is not a good indicator of the effectiveness of screening, and it also omits the page where the rate of overdiagnosis is given as 20 to 50%. Indicating a rate at its low range is an option in a document, but the high range must also be honestly given.

What does the NIH say specifically regarding these two parameters ?

On overdiagnosis rates https://www.cancer.gov/types/breast/hp/breast-screening-pdq#_13_toc
Magnitude of Effect: Between 20% and 50% of screen-detected cancers represent overdiagnosis based on patient age, life expectancy, and tumor type (ductal carcinoma in situ and/or invasive).[11,12] These estimates are based on two imperfect analytic methods:[11,13]
Long-term follow-up of RCTs of screening.
The calculation of excess incidence in large screening programs.[11,12]
Study Design: RCTs, descriptive, population-based comparisons, autopsy series, and series of mammary reduction specimens.

On survival and screening effectiveness https://www.cancer.gov/about-cancer/screening/research/what-screening-statistics-mean

Much of the confusion surrounding the benefits of screening comes from interpreting the statistics that are often used to describe the results of screening studies. An improvement in survival—how long a person lives after a cancer diagnosis—among people who have undergone a cancer screening test is often taken to imply that the test saves lives.

But survival cannot be used accurately for this purpose because of several sources of bias.

5) The “choice of screening” is no longer mentioned in the booklet title, and the last chapter on screening options (to accept or do not accept) has been removed and replaced with testimonials on the benefits (a reassuring example of a screening that "saved" a woman's life, another of a woman who, not having been screened, might have received a more aggressive treatment)

This option of choice was included at the end of the 2017 booklet:

6) There is still no visual pictogram (as requested by women citizens), that illustrates in absolute numbers the benefits and the harms, to have a global vision and to allow the women to make their choice.

7) The harms of screening continue to be named "limitations" (page 13 of the booklet), whereas the term in English is "harms".

"Limitations" rather implies the inability to detect correctly.

8) Messages from personalities (president of INCa), authorities (recommendation in Europe), appeals to fear (if you don't get screened...), are used as influence techniques.

The positive points.

1) A specific page that groups screening harms (also present in 2017, but not grouped together and without a clear title for each harm).

2) Better organization of information on prevention (risk and protective factors, table on cancer statistics related to each risk factor, page 9)

3) Easier to read, a more visual document

4) The addition of the midwife (alternative to the general practitioner or gynecologist) in the follow-up clinical examinations and to answer questions on screening.

Comparison of the texts of the two booklets in the table

Download / Télécharger

In conclusion

This booklet, ideally corrected to address the persistent deficiencies that Sophie identified for us, may be sent with each screening invitation, not just at age 50.

In the leaflet for successive screenings (beyond the age of 50), the harms of screening and recommendations on prevention have been omitted, resulting in abbreviated and insufficient information.

Women must now be completely and appropriately informed, as requested during the citizen consultation, and that for the rest of their lives of “screened women”.

Those women who had their initial screening before 2022 will never receive this information.

This can be implemented without too much difficulty by simply replacing the leaflet planned for the next invitations by this booklet, duly completed and corrected for its weaknesses.

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.

A new EU approach to cancer screening

September 22, 2022 - Abstract Dr. C.Bour


Within the framework of the European program of the fight against cancer and cancer screening, which will be included in a large European plan, the European Commission proposes an extension and/or a restart of certain screenings and an implementation of new ones.
The objective is that by 2025, 90% of the EU population will be screened for breast, prostate, cervical and colorectal cancer. Lung and stomach cancer screenings are also included, although no conclusive studies exist for the latter.

Regarding funding: “Europe's Beating Cancer Plan is supported using the whole range of Commission funding instruments, with a total of €4 billion being earmarked for actions addressing cancer. This includes around € 38.5 million committed from the EU4Health programme for screening-related projects and € 60 million under the Horizon Europe. The Commission will propose additional funding for cancer screening under the 2023 EU4Health programme.”

A blatant disregard for acquired knowledge and established recommendations

1° breast cancer

The Commission wishes to extend breast cancer screening to younger women, including women starting at 45 years of age.

However, a British trial, the UK Age Trial, delivered its results in 2021. After 23 years, the results of the UK Age Trial no longer showed a significant decrease in the number of deaths from breast cancer in women screened between the ages of 40 and 49. The authors of the trial concluded: "Overall, there was no significant reduction in breast cancer mortality in the intervention group compared with the control group.”
The results also showed no reduction in total mortality (or all-cause mortality).
The justification for this extending screening to a younger age is as brief as it is unscientific:

“The GDG (development group of these guidelines)  agreed this recommendation by consensus with no need for voting.”
“The decision on this recommendation takes into account the balance between desirable and undesirable effects that probably favours organised mammography screening for women aged 45 to 49 in the context of moderate certainty of the evidence.”

Yet the downloadable 2016 PDF detailed the doubts that exist for this screening: "Mammography, compared with no screening, did not significantly reduce the risk of breast cancer mortality..... in women invited to screening during 16.4 years of follow-up."...
"Mammography, compared with no screening, reduced the risk of stage IIA or higher breast cancer (46 fewer cases of breast cancer per 100,000 women ...but did not reduce the risk of all-cause mortality."
(Recall that overall mortality includes all elements of healthcare, so also the effects of treatment, overdiagnosis, and overtreatment. This figure is more meaningful because any cancer detected will be treated; the treatments themselves sometimes cause deaths, which will be included and encompassed in the 'all-cause mortality,' thus better reflecting the reality of screening).

"Adverse events:
Women aged 40-74 randomized to 'invitation to screening' were more likely to undergo mastectomy....
Overdiagnosis is estimated to be 12.4% (moderate quality evidence) from a population perspective and 22.7% from the perspective of a woman invited to screening (moderate quality evidence).
The number of false positives will depend on age at the first screening. Estimated cumulative risk of false-positive screening: The rate of women aged 50 to 69 years who underwent 10 biennial screenings was 19.7%. However, higher false-positive rates were observed among women younger than 50 years than among women aged 50 to 69 years.
In addition, 2.2% of women had a needle biopsy after the initial screening mammogram.
False-positive mammograms are also associated with greater anxiety and distress about breast cancer as well as negative psychological consequences that can last up to three years (low quality evidence). ..."

2.Prostate cancer

The Commission proposes introducing a prostate-specific antigen (PSA) test - similar to a blood test - in men up to age 70, combined with additional magnetic resonance imaging (MRI) as a follow-up test.

Yet, prostate cancer screening has been long debated and is not longer recommended by the HAS since 2013- https://www.has-sante.fr/jcms/c_1623737/fr/detection-precoce-du-cancer-de-la-prostate
"the HAS recalls that the implementation of a screening program for prostate cancer using total serum PSA measurement is not recommended, either in the general population or in men at high risk."

The lack of benefit in mortality reduction and significant overdiagnosis motivated this decision. More explanation here:


The extension of screening to the younger age group is a step forward from 2019, when, regarding the 45-49 age group, the GDR (expert panel proposing the recommendations) suggested at that time a triennial or biennial mammographic screening in the context of an organized screening program, mentioning a low level of certainty.

In the meantime, the MyPEBS study has been set up to test the possibility of more targeted screening since it must be admitted that the current screening does not work as expected: "After analysis of all the components, the final objective of Mypebs is to provide the best recommendations for the best breast cancer screening strategy in Europe.
The MyPEBS promoters' argument also states: "A major challenge is to make women more informed and more active in their screening decisions, as clearly recognized by several international studies. Indeed, a major concern of national screening programs in all participating countries is to promote informed choices about decisions to participate in screening and subsequent treatment options. Informed choices require that good quality, relevant information be provided to women so that they can make decisions consistent with their values."

So it appears that the EU sees no contradiction in funding a €12M study to achieve more precise, risk-based screening and, on the other hand, expanding the age ranges for screening without evidence, even before MyPEBS has delivered its results...
Or else there is no contradiction, and the MyPEBS study is meant to achieve this, to finally impose screening to all women, with an extension of the age to younger age groups as early as 40 years old as we already figured...?

Read: https://cancer-rose.fr/my-pebs/2019/06/13/argument-english/

These new EU recommendations just jump to the front.
This current 2021 EU report states that for the 45-49 age range, "full details, including downloadable supporting documents for health professionals, will be available soon."

We hope these will be real scientific justifications and that the promise made to citizens after the French citizen consultation to provide support tools for an informed decision, including the decision not to be screened, will not be forgotten.

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.

Liquid biopsies, the Grail?

Synthesis Dr. C.Bour, September 15, 2022

Main article

Article by Brenna Miller

The Damocles syndrome


Early cancer detection is and remains a Grail for which we have absolute faith in technology. Despite all the failures of screening (melanoma, thyroid, prostate, breast) to overcome cancer and its, unfortunately, most serious forms[1], we nevertheless remain convinced that if we detected all cancerous cells, we could "beat" the disease.
Studies show that the small gains in mortality in cancerology are not due to detection but almost essential to progress in treating advanced forms. Breast cancer is an example.

The media is often the spokesperson for "spectacular discoveries," and we have already reported on the problem of the media coverage of scientific innovations, such as screening and blood tests (liquid biopsies) for early detection of cancer, which was the subject of a study published in JAMA in 2021.

With the multiplication of screenings, most of them failing to decrease overall mortality and reduce the most advanced forms of cancers, our societies have ended up with two kinds of diseases.
On the one hand, diseases that are experienced by the patient, with specific symptoms and identified by the clinician, and on the other hand, conditions that are not experienced but detected by screening and defined as diseases. In the latter case, it is complicated to determine what a patient is. A person in whom the pathologist has found a cancerous cell under his microscope?  A person with a cancerous cell cluster in an organ that will never affect it? A person with a polyp that might have become cancerous one day?

The paradox is that with mass screening and no particular selection, more and more people are declared "sick" without being so, and above all, "cured" before ever being clinically ill. Thanks to the biomedical miracle, they are even treated and then cured of a disease they would never have known. If this is not progress... The problem is that, on the one hand, the treatments themselves can make people sick. On the other hand, the knowledge of their "cancer" exposes people to a suicide rate five times higher, with a maximum observed just after the diagnosis's announcement, whether it is a detected lesion or a "real" clinical cancer. The announcement multiplies by 12 the risk of death by cardiovascular accident.

We (re)-talk about liquid biopsies

An article in La Croix (French newspaper) announces, as did other media recently (Futura Science, Tops Santé, etc.), a blood test consisting of detecting tumor DNA circulating in the blood and thus making it possible to detect 50 types of cancers.

But, as explained above, early detection of cancers does not mean an automatic cure and does not protect against false positives or unnecessary detections.

This is the concern expressed by Gilbert Welsch and Barnett Kramer in an article published in the journal STAT.
Welsch, a general internist and senior researcher at the Center for Surgery and Public Health at Brigham and Women's Hospital in Boston, details this notion in the article dedicated to liquid biopsies, with a critical analysis that you can find here in STAT+
Barnett Kramer is an oncologist, member of the Lisa Schwartz Foundation for Truth in Medicine, and former director of the Division of Cancer Prevention at the National Cancer Institute.

What are liquid biopsies?

A liquid biopsy allows the detection of circulating tumor cells dislodged from a primary tumor or even from metastases and carried in the vascular system, as well as the circulating DNA of these circulating tumor cells. The hope is to be able to detect cancer before its expression.

It was back in 2015 in the United States when members of Congress introduced a bill requiring US Medicare to cover a costly cancer screening test offered to the entire population, but for which so far, there is no scientific evidence that the procedure saves lives.
The American Cancer Society, an American nonprofit organization founded in 1913 to fight cancer and firmly in favor of screening, approved the project, arguing that this expensive and unproven test would solve health disparities.

The two American authors then asked two fundamental questions:
Do liquid biopsies work as advertised?
If liquid biopsies are effective, are they effective enough to be worthwhile?
Finally, a third question emerges: What about the reduction in disparities that the American Cancer Society claims?

Do liquid biopsies work as advertised?

It is claimed, say the authors, like a mantra, regularly repeated in a loop by opinion leaders and media who do not care about the controversy, that 90% of cancers detected very early are cured. This is not, nevertheless, proof that screening saves lives...

What does the notion of 5-year survival mean?

The "90% survival at five years" for cancers is true, but only for cancers with a very good prognosis and those that should never have been discovered and would never have made anyone sick. For cancer that would never have killed its host, it is quite normal that the host is alive after 5 years. It is also true that cancers with a good prognosis have a better survival rate than those with a poor prognosis and metastatic disease. Still, the real question is: is screening capable of discovering these latter cancers in due time, the ones we should be catching because they kill? And this is where the problem lies (see ref 1)...

First, say Welsch and Kramer", early detection of some cancers may not be possible. Despite four decades of mammography screening, for example, the incidence of metastatic breast cancer remains virtually unchanged. Very aggressive cancers have often spread by the time they become detectable." Indeed, aggressive, metastatic cancers do not arise from smaller or lower-grade cancers; they are lesions that are aggressive from the start and have such a molecular component that they have already metastasized in the body; even when they can be detected, they are large at the time of diagnosis because they are very fast. Lanning's study explains the mechanics of cancer very well.

"Second, although earlier detection of some potentially aggressive cancers is possible, early treatment may not change the time of death. Survival statistics hide this possibility."
This is called lead time, which is explained in detail here.
Detection advances the "birth date" of cancer and thus benefits survival statistics but has no impact on people's longevity. It is an optical illusion.

And third, survival statistics are inflated by overdiagnosis, i.e., the unnecessary detection of lesions that would never have killed.
According to Prof. Welsch, "High survival statistics may indicate a problem. For example, the 90% 5-year survival for early-stage cancers includes many cancers detected by blood tests, such as prostate cancer and PSA testing, or by imaging, such as breast cancer and mammography, that were not intended to progress to late-stage cancer or cause death. Overdiagnosis - common in breast, prostate, thyroid, and melanoma skin cancers - significantly inflates survival rates. Higher survival due to overdiagnosis is not a benefit, but harm, with more people, diagnosed and treated for "cancers" that were never going to cause problems."

If liquid biopsies are effective, are they effective enough to make them worthwhile?

We quote below what the two scientists write:

"Even if medical intervention is effective, it is essential to evaluate its side effects. Aspirin, for example, is effective in preventing heart attacks and strokes but not enough in the general population to justify the associated harms, such as brain and intestinal bleeding.
Liquid biopsies will have unintended disadvantages: more tests, more treatments, and the psychological and physical problems that come with them. Some people will be told they have a "cancer signal" - triggering fear and more tests - only to learn later that it was a false alarm. Others will be overdiagnosed and treated for cancers that otherwise would never have worried them. Some will be affected by the treatment; some may even die.
Still, others will have significant cancers discovered earlier than they would have without the liquid biopsy but will not live longer. They will be subjected to the toxicity of cancer therapies earlier, at a time when they would otherwise have no symptoms. These side effects exist in all cancer screening programs. But multicancer liquid biopsy screening has one of its own: While it may be evident that a person has cancer, it is not always clear where that cancer is. Imagine being told you have cancer, but no one knows what type it is.
No one knows how common these side effects are because these tests have not been rigorously studied. But a bad test is as bad as a wrong drug. That's another reason why a randomized trial is needed - not just to determine if liquid biopsies provide benefits but also to determine how often they cause harm.
One thing we know about liquid biopsy screening is that it will be costly."

One test, the Galleri test, for example, costs $949. If it's recommended every year for people 50 and older, Welsch calculates, with 100 million Americans in that age range, that would be about $100 billion a year, he says.
Moreover, additional examinations and other tests will be required to search for and confirm cancer that the liquid biopsy suggests, and the number of medical consultations will be multiplied.

Because if there are wandering tumor cells, cancer must still be found.

Reduction of disparities?

Here again, the two researchers are very doubtful...

"Those who want to address the significant drivers of health disparities should be less concerned with the Medicare population and more concerned with people under age 65, especially where the disparities really start: among young adults and children. And they should be less concerned with medical interventions such as cancer screening and more concerned with the real determinants of health, such as diet, housing, and income security.
Increased mammograms and colonoscopies have not solved the health effects of poverty, and liquid biopsies won't solve them."

In another article published in the Boston Globe, Welsch cites the example of the Galleri test, which has avoided the FDA approval process (the U.S. Food and Drug Administration, which verifies and approves the marketing of drugs) through a waiver. Galleri is sold directly to consumers for $949 per person.
"The company that sells Galleri," says Welsch, "recommends that people take the test once a year. Let's do the math. Given that there are about 60 million Medicare beneficiaries, that would be about $60 billion a year. That would represent a 7% increase in total Medicare spending ¬- to be passed on to taxpayers and/or Medicare beneficiaries in the form of higher premiums.
All this for one test. And no one knows if that test helps people live longer or better."

What should be done?

For G.Welsch, there is only one way to test liquid biopsies on their effectiveness in detecting cancers early: to conduct a randomized trial in which participants are divided into two groups. One group is screened regularly; the other is not. The participants are then followed for about ten years, counting the number of deaths in each group. Randomized controlled trials are the "gold standard" of scientific studies and are a proven method. England's National Health Service (NHS) is currently recruiting 140,000 people for such a trial. The most relevant outcome to measure would be the number of deaths in each group.

The US National Cancer Institute is planning a randomized trial of liquid biopsy screening. Ironically, says G. Welsch in the Boston Globe, the adoption of Medicare coverage for these tests would hamper this trial "because of a dynamic we've already seen. In the 1990s, many doctors and patients believed that a transplant of one's bone marrow was an effective treatment for metastatic breast cancer. The press focused on young women who were dying of aggressive cancer without access to this "life-saving" procedure ...... The presumption of benefit was so strong that researchers had difficulty finding volunteers to participate in studies to determine whether the procedure worked. Everyone already assumed it did. But it didn't.
.... "randomized trials finally showed that bone marrow transplants didn't help women live longer. And they certainly didn't live better. Tens of thousands of women underwent an arduous procedure, often complicated by anemia, infection, and diarrhea. And some died as a result."

So don't put the cart before the horse; it's urgent...wait, the researcher implores Congress at the end of the article to let the American National Cancer Institute and the US Preventive Services Task Force do their work. (USPSTF: group mandated to review the evidence and make recommendations on prevention devices).

Article by Brenna Miller, Lown Institute

Finally, you can find here the summary of the facts, written by Brenna Miller, a health communication specialist at the Lown Institute. She holds a master's degree in public health from Tufts University School of Medicine.

The Lown Institute is "a nonpartisan think tank that advocates bold ideas for a fair and caring health care system."

The author refers to Theranos, an American health technology company that supposedly developed the first liquid biopsy tests without independent evaluations or scientific publications and whose executives were finally indicted in 2018 for massive fraud.

The Damocles Syndrome
Blood Tests That Detect Cancers Create Risks for Those Who Use Them

The New York Times, By Gina Kolata on June 10, 2022


The article features testimonials highlighting the benefits of these tests for patients, but also the risks they pose, especially if, as is currently the case, companies don't wait for a green light from legislators, shortcut approvals and sell the tests directly to consumers.

"Jim Ford considers himself a lucky man: An experimental blood test found his pancreatic cancer when it was at an early stage. It is among the deadliest of all common cancers and is too often found too late. After scans, a biopsy and surgery, then chemotherapy and radiation, Mr. Ford, 77, who lives in Sacramento, has no detectable cancer.
“As my doctor said, I hit the lottery,” he said."

The Damocles syndrome

But there are other testimonials and less enthusiastic comments on the tests:

“When Susan Iorio Bell, 73, a nurse who lives in Forty Fort, Pa., saw an ad on Facebook recruiting women her age for a study of a cancer blood test, she immediately signed up. It fit with her advocacy for preventive medicine and her belief in clinical trials.
The study was of a test, now owned by Exact Sciences, that involved women who are patients with Geisinger, a large health care network. The test looks for proteins and DNA shed by tumors. Ms. Bell’s result was troubling: Alpha-fetoprotein turned up in her blood, which can signal liver or ovarian cancer. She was worried — her father had had colon cancer and her mother had breast cancer. Ms. Bell had seen what happened when patients get a dire prognosis. “All of a sudden, your life can be changed overnight,” she said. But a PET scan and abdominal M.R.I. failed to find a tumor. Is the test result a false positive, or does she have a tumor too small to be seen? For now, it is impossible to know. All Ms. Bell can do is have regular cancer screenings and monitoring of her liver function. “I just go day by day,” she said. “I am a faith-based person and believe God has a plan for me. Good or bad, it’s his will.”
Some cancer experts say Ms. Bell’s experience exemplifies a concern with the blood tests. The situation may involve only a small percentage of people because most who are tested will be told their test did not find cancer.
Among those whose tests detect cancer, scans or biopsies can often locate it. But Dr. Susan Domchek, a breast cancer researcher at the University of Pennsylvania, warned that when large numbers of people get tested, false positives become “a real problem,” adding, “we need to know what to do with those results and what they mean.”

Dr. Daniel Hayes, a breast cancer researcher at the University of Michigan, refers to the situation as a Damocles syndrome: “You’ve got this thing hanging over your head, but you don’t know what to do about it.”

Donald Berry, a statistician at MD Anderson Cancer Center in Houston, shares his experience and doubts. When GRAIL was first formed, its leaders invited him, to be on its scientific advisory board.
“They said they needed a skeptic,” Dr. Berry said. “I told them I was a skeptic and I was quite negative. I told them there was this real hurdle — they will have to run very large clinical trials and the endpoint must be survival. They have to show that detecting cancer early is more than just detecting cancer early. It has to mean something.”
A few years later, the company restructured its scientific advisory board to include many new experts, and Dr. Berry is no longer a member. He is not sure why.
“Being generous, I’d say they no longer needed my expertise,” Dr. Berry said. “Being realistic, they got tired of hearing my complaints that finding cancer early was not enough.”

Reasons for reluctance

Difficult questions from Donald Berry concern overdiagnosis: "finding small tumors that would never have been noticed and may not have caused any harm. Some cancers simply fail to grow or are destroyed by the body’s immune system.
But without knowing if the cancer is dangerous, it will be treated as though it is, subjecting people to therapies that are often difficult or debilitating and may be unnecessary. Dr. Kramer said this also happens with standard screening tests, which can result in the removal of thyroid glands, breasts or prostates for small tumors that are actually harmless."

Another issue is the efficiency of detection for these tests, especially in the most aggressive cancers, according to Dr. Kramer, an oncologist, member of the Lisa Schwartz Foundation for Truth in Medicine, and former director of the Division of Cancer Prevention at the U.S. National Cancer Institute.
“We will dip more and more deeply into the iceberg of disease,” Dr. Kramer said, finding “lesions that look like a cancer to the pathologist but may not have the same natural history at all.” It may not even be possible to find the most aggressive cancers early enough for a cure, Dr. Kramer added. The tumors that shed the most DNA and proteins into the blood are the largest tumors.”

The article concludes with the opinion of the aforementioned statistician Dr. Berry:
“Dr. Berry, though, is not assuaged and fears that the public’s faith in early detection which, he says, “is like a religion,” will rule the day, even without good evidence.“Everybody loves early detection, but it comes with harms,” Dr. Berry said. “The harms, we know,” he added. “The benefits are very uncertain.”

“But a definitive study to determine whether the tests prevent cancer deaths would have to involve more than a million healthy adults randomly assigned to have an annual blood test for cancer or not” explains the article. “Results would take a decade or longer”.

Will the public, the media, the companies marketing the tests have the patience to wait?


[1] Non reduction of metastatic cancers since screening for breast and prostate cancer, studies:

Autier P, Boniol M, Koechlin A, Pizot C, Boniol M. Effective- ness of and overdiagnosis from mammography screening in the Netherlands: population based study. BMJ 2017;359:j5224.

Autier P, Boniol M, Middleton R, Dore JF, Hery C, Zheng T, et al. Advanced breast cancer incidence following population- based mammographic screening. Ann Oncol 2011;22(8): 1726e35.

Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012; 367(21):1998e2005.

De Glas NA, de Craen AJ, Bastiaannet E, Op ’t Land EG, Kiderlen M, van de Water W, et al. Effect of implementation of the mass breast cancer screening programme in older women in The Netherlands: population based study. Bmj 2014;349:g5410.

Autier P, Boniol M. The incidence of advanced breast cancer in the West Midlands, United Kingdom. Eur J Cancer Prev 2012; 21(3):217e21.

Nederend J, Duijm LE, Voogd AC, Groenewoud JH, Jansen FH, Louwman MW. Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study. Breast Cancer Res 2012;14(1):R10.

Lousdal ML, Kristiansen IS, Moller B, Stovring H. Trends in breast cancer stage distribution before, during and after intro- duction of a screening programme in Norway. Eur J Public Health 2014;24(6):1017e22.

Johnson RH, Chien FL, Bleyer A. Incidence of breast cancer with distant Involvement among women in the United States, 1976 to 2009. JAm Med Assoc 2013;309(8):800e5.

Esserman L, Shieh Y, Thompson I. Rethinking screening for breast cancer and prostate cancer. Jama 2009;302(15):1685e92. [53] Jorgensen K, Gøtzsche PC, Kalager M, Zahl P. Breast cancer screening in Denmark: a cohort study of tumor size and over-diagnosis. Ann Intern Med 2017 Mar 7;166(5):313e23.

Welch HG, Gorski DH, Albertsen PC. Trends in metastatic breast and prostate cancer dlessons in cancer dynamics. N. Engl JMed 2015;373(18):1685e7.

Di Meglio A, Freedman RA, Lin NU, Barry WT, Metzger-Filho O, Keating NL, et al. Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis. Breast Cancer Res Treat 2016;157(3):587e96.

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The risks of screening: an elephant in the room

This article proposes a synthesis of two points of view of Dutch academics written for a medical journal, then the translation of each piece is accessible by clicking on the authors' names.

A critical look at screening

Article by R. Giard

Article by Y. van der Graaf

A critical look at screening

Synthesis by C.Bour

In June, two Dutch academics each wrote a critical review of screening with the contemporary perspective of 2022, published by the medical journal Nederlands Tijdschrift voor Geneeskunde (NTvG).

NTvG is the leading medical journal in the Netherlands, published weekly, and one of the oldest journals in the world, based in Amsterdam. The journal aims to create a global medium for health professionals to exchange ideas, knowledge, and opinions and publish reviews and commentaries of research articles.

The editor-in-chief is Yolanda van der Graaf, author of one of the two perspectives. Yolanda van der Graaf is a professor emeritus at the University of Utrecht and a clinical epidemiologist. Her article describes the hidden risks of screening.
van der Graaf Y. De verhulde risico’s van screening [The hidden risks of screening]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6760. Dutch. PMID: 35899724.

Raimond Giard is a professor emeritus, clinical pathologist, and clinical epidemiologist in Rotterdam and has written a critical view of screening under the title “A critical view on cancer screening: do we see the elephant in the room?"
Giard RWM. Kritische blik op kankerscreening [A critical view on cancer screening: do we see the elephant in the room?]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6926. Dutch. PMID: 35899737.

Key points common to both authors

1° a new approach to screening is needed

For these two authors, there is a concrete system based on which it has been possible to decide that it is useful to introduce cancer screening: the Wilson and Jungner criteria published in 1968, which the WHO uses as a reference. But there is no system for deciding when it is preferable to stop screening or change the approach now that we are confronted with certain realities of screening and know its drawbacks.
For both authors, the criteria are a bit dated and should be reconsidered and re-evaluated.
For van de Graaf, there is even a serious lack of compliance with these criteria for some screenings, with some not complying with the conditions set out by Wilson and Jungner.

But what does the WHO use as criteria to determine the validity of a screening? The 10 criteria retained by the WHO are :

- The disease studied must be a significant public health problem
- The natural history of the disease must be known
- A diagnostic technique must be able to visualize the early stage of the disease
- The results of the treatment at an early stage of the disease must be superior to those obtained at an advanced stage
- Sensitivity and specificity of the screening test should be optimal
- The screening test must be acceptable to the population
- The methods for diagnosis and treatment of abnormalities found in screening must be acceptable
- The screening test should be repeatable at regular intervals if necessary
- The physical and psychological burden of screening should be less than the expected benefits
- The economic cost of a screening program should be outweighed by the expected benefits

For the Dutch authors, certain diseases are no longer a significant public health problem. Certain screening tests are no longer acceptable to the population, given their adverse effects. The physical and psychological harms are no longer lower than the expected benefits, which leads them to conclude that participants in screening programs should be given honest information, that if the benefits of screening are indeed overestimated and the harms underestimated, it is certainly time to reconsider cancer screening with an open and independent vision.

Several studies have argued that a universal population screening approach, particularly for breast cancer, is no longer tenable," says Giard. We need a new and independent evaluation of screening practices.

This analysis had already been expressed in a publication in CMAJ in 2018 that we had synthesized and commented on.

Wilson and Jungner's principles are getting dated, according to the authors of the CMAJ article. There is currently a need, they said, for a clear and consistent rationale to guide the use of various types of evidence toward a decision to screen. It is time to modernize these principles for explaining and discussing population-based screening. This modernization should contribute to informed decisions and better information about screening for the population in the future.
Our commentary echoed this, saying that the principle of informed choice, promotion of autonomy, and protection of the rights of participants in screening is simple and inexpensive to implement.
Pictograms with absolute numbers (using a consistent denominator, such as benefits and harms per 1,000 screened) and visuals using the same scale for information on gains and harms are evidence-based.

2° What would be the right questions to ask, according to Giard and van de Graaf?

According to R. Giard, good reasons to reconsider screening could include

- Has there been any change in the incidence of the disease?
- Has the treatment of the disease become more effective?
- Are there better diagnostic methods available today?
- Are there new, more reliable results from research on the effects of screening?
- Do we now know better and more accurately what the adverse effects are?
- Can we assess the disease risk more accurately and screen more specifically?

A significant question to ask is: is screening for a specific disease worthwhile? Y. van der Graaf uses the example of lung cancer screening, a program currently under evaluation."A long time ago," she writes, "we decided that we were willing to pay 20,000 euros for a year of life saved, but now the question is what else we could do with that money. Virtually all smoking cessation interventions are feasible for a threshold value well below €20,000 per life year saved. By far, the most health benefits can be achieved in the field of smoking cessation in the Netherlands. The health benefits of screening programs are minimal compared to these."

3°Overestimation of the risk and overestimation of the impact of screening

Y de Graaf explains: "Only 3% of women die of breast cancer. The risk of dying from colon cancer is "only" 2%."
(The risk of dying from cancer must therefore be put into perspective with other probabilities of death, such as cardiovascular disease, which is 6X more likely than dying from breast cancer for women, Editor's note)

Most breast cancers do not cause death in women, even without screening. What matters is the risk of dying prematurely from breast cancer and how that risk is reduced by participation in screening," she writes, "which means knowing the real impact of screening on mortality.
What is essential is to know how many people need to be screened to prevent 1 death from cancer in question. For example, for breast cancer: "For every breast cancer death you prevent through screening, 1000 women need to be screened regularly. By implementing a screening program, over 100 women are treated unnecessarily. So the odds of unnecessary treatment are tens of times higher than that of a woman obtaining benefits from screening. The main problem is that this number is not adequately communicated to potential participants to screening."

In her article, Ms van der Graaf explains in detail the distortion of the perception of the beneficial effect of screening in the population and among health professionals, the benefits and impacts being largely overestimated and the adverse effects ignored.

For both authors, the adverse effects of screening, i.e., false alarms, over-diagnosis, and over-treatment, are major issues. They are high and should no longer be ignored.

For R. Giard, "it is breast cancer screening, in particular, that does not seem to live up to its supposed promise. Even after many years of screening, the incidence of advanced breast cancer has not decreased."
In Switzerland, Hong Kong, and France (see our articles under "citizen consultation"), among others, critical reports have been published calling for the abandonment of breast cancer screening in its current form.
Several studies have argued that a universal population screening approach is no longer defensible, particularly for breast cancer."
Van der Graaf writes, "most importantly, potential participants must be informed of the potential harms and small health benefits."

4° The financial stakes and the need for independent evaluation

But people's fear of cancer brings in a lot of money and demands many systematic examinations such as whole-body scans, which Y. van der Graaf explains are useless.
The practice of systematic scans is an excellent revenue model because the provider only makes diagnoses, with an excessive amount of unexpected results that nobody knows what to do with, useless for the patient but leading to a succession of other examinations. This is called "irrelevant results" in her article, i.e., fortuitous discoveries of uninvestigated and useless anomalies, whose discovery rate is extremely high and which will cause cascades of other investigations or systematic patient monitoring.

For both authors, screening must be evaluated by independent scientists, not by people who have been doing screening for decades and who have conflicts of interest.
It is also necessary to combat the proliferation of screening programs for which there is no scientific evidence, and financial gain is the priority.
According to Giard, re-evaluations of screening would require appropriate research teams, "broad-based," not only consisting of physicians but also social scientists, ethicists, methodologists, and health economists, and excluding those with financial implications for screening.

Article by R. Giard
A critical eye on cancer screening- Do we see the elephant in the room?

Giard RWM. Kritische blik op kankerscreening [A critical view on cancer screening: do we see the elephant in the room?]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6926. Dutch. PMID: 35899737.

'A great deal of intelligence can be invested in ignorance when the need for illusion is deep'
Saul Bellow, To Jerusalem and back


Cancer screening promises health benefits, but it also delivers harm and costs. A substantial problem is the overdiagnosis of tumors not needing treatment. There are well-established principles for starting cancer screening, but we also need periodic evaluations and stopping rules. For that, we must have the results of methodic empirical studies with proper estimates of benefits and harms. Proponents of screening emphasize its advantages but hold back on its drawbacks. Several studies have argued that a universal population screening approach is no longer tenable, especially for breast cancer. We need a fresh and independent assessment of screening practices.

Conflict of interest and financial support: none declared.

Shouldn't we be taking a fresh look at cancer screening? 1-3 There is a system based on which it can be decided that it is useful to introduce cancer screening - see the WHO criteria of Wilson and Jungner - but not to determine when it would be better to stop or to adopt a different approach. For that, one needs both the correct methodology and the right data. Such an evaluation, intended to separate illusions from reality, should be periodically repeated.4

Cancer screening, part of public health care, involves significant conflicts of interest and biases. Proponents and opponents of screening can find outcomes in the pervasive medical-scientific literature on the subject that fit well with their stance. Rethinking its usefulness and necessity, therefore, requires independent and methodical researchers.3,4
Good reasons to reconsider may include: did changes occur in disease incidence?
Has the treatment of the disease become more effective? Are there better diagnostic methods now? Are there new, more reliable results from research on the effects of screening? Do we now know better and more precisely what the harms are? Can we assess the risk of disease more accurately and, therefore, screen more accurately?

Over- and underdiagnosis

As discussed in the NTvG, cancer screening tests show deficiencies in over- and underdiagnosis.5-7 The frequency of overdiagnosis of breast cancer is variably reported between 0 and 50%. 8 And the same research figures can be interpreted differently depending on whether you are an advocate or critic of screening.9 But there is no doubt that significant overdiagnosis exists; it occurs in at least 20% of all mammary carcinomas detected during screening.1,5

Underdiagnosis is evidenced by the occurrence of interval cancers, a possible "failure" of the screening test. As a solution to this is the search for additional or improved technology. In breast cancer screening, more sensitive imaging techniques are being sought, such as digital mammographic tomosynthesis and MRI, and the application of artificial intelligence in assessing mammograms. The danger is that with more sensitive diagnostics, even more, and especially smaller, abnormalities will be detected, resulting in even more overdiagnosis.10

What do you need to make a good assessment?

To properly assess the effects of screening, you need sound empirical data and especially outcome measures that are valid, reproducible, and sufficiently specific.11 Disease detection is not the goal, but a means. The intention is to gain life years or increased chances of cure. Cancer-specific mortality drops undeniably due to screening, but the absolute mortality within screened populations appears to decrease little or not at all. And there is still the question of whether an alleged survival is really the result of screening.5

Careful consideration of beneficial and adverse effects is a task for both those conducting the population screening and those participating in it.3,4 National screening programmes have been designed to ensure that the benefits of screening are carefully considered.3,4 National guidelines for cancer screening should explicitly state the desired relevant outcome measures. Still, they should also address the essential tradeoffs between the benefits and harms of that particular population screening. A recent systematic review showed that only a minority of those guidelines explicitly address this issue.12

Potential participants should be able to make an informed decision about whether or not to participate in screening. But who provides balanced information about the benefits and harms and how to address these? Information about the consequences of overdiagnosis, particularly the need for further invasive tests and surgical intervention, has been shown to make women more reluctant to participate in breast cancer screening.13

Evaluation of population-based cancer screening

Cancer is a heterogeneous disease, and population screening is a complex procedure. Divergent variables determine its outcomes. That is why a comprehensive evaluation is so complicated: what are its aims, who will do it, what will they investigate, and how? This requires an appropriate, i.e., broadly based, research team, that includes social scientists, ethicists, methodologists, and health economists in addition to medical professionals. Persons with financial or institutional involvement in screening should be excluded from such a team. 4

Essential to such an evaluation is greater participation by the target screening group: after all, they are confronted with negative consequences. How do they weigh up all the pros and cons? A Norwegian study, for example, showed that in breast cancer screening, the consequences of overdiagnosis and overtreatment negatively affected the quality of life of the women, expressed in quality-adjusted life years (qaly's).
Over and again, the harms of screening are not adequately considered; I call this the elephant in the room.1-3


Breast cancer screening, in particular, does not seem to be delivering on its supposed promises. Even after many years of screening, contrary to expectations, it appeared that the frequency of advanced breast cancers did not decrease.5 In countries including Switzerland, Hong Kong, and France, critical reports appeared calling for breast cancer screening in its current form to be stopped.2,4
Twenty years ago, the NTvG already organized a conference with critical reflections on cancer screening.
The problems identified and the conclusions reached then are still relevant today.15 If the benefits of screening are indeed overestimated and the harms underestimated,  it is time to reconsider cancer screening in our country with an open-minded and independent view.

Conflict of interest and financial support: none declared.
Online article and comment at ntvg.nl/D6926
Rotterdam: em.prof.dr. R.W.M. Giard, clinical pathologist (n.p.), clinical epidemiologist and lawyer.
Contact: R.W.M. Giard (raimondgiard@gmail.com)
Conflict of interest and financial support: none reported.
Accepted on May 18, 2022
Cite as: Ned Tijdschr Geneeskd. 2022;166:D6926


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2. Hochman M, Cohen P. Cancer screening: no longer the default. J Gen Intern Med. 2021;36:525-6. doi:10.1007/s11606-020-05781-7. Medline

3. Van der Graaf Y. De verhulde risico’s van screening . Ned Tijdschr Geneeskd. 2022;166:D6760.

4. Ropers FG, Barratt A, Wilt TJ, et al. Health screening needs independent regular re-evaluation. BMJ. 2021;374:n2049.doi:10.1136/bmj.n2049. Medline

5. Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018;90:34-62.doi:10.1016/j.ejca.2017.11.002. Medline

6. Van der Graaf Y. De verhulde risico's van screening. Ned Tijdschr Geneeskd. 2022;166:D6760.

7. Krom A, Dekkers OM, Ploem MC. Verlies de nadelen van screening niet uit het oog: zorgen over wijziging Wet op hetbevolkingsonderzoek. Ned Tijdschr Geneeskd. 2022;166:D6701.

8. Chaltiel D, Hill C. Estimations of overdiagnosis in breast cancer screening vary between 0% and over 50%: why? BMJ Open.2021;11:e046353. doi:10.1136/bmjopen-2020-046353. Medline

9. Njor SH, Paci E, Rebolj M. As you like it: How the same data can support manifold views of overdiagnosis in breast cancer screening.Int J Cancer. 2018;143:1287-94. doi:10.1002/ijc.31420. Medline

10. Jatoi I, Pinsky PF. Breast cancer screening trials: endpoints and overdiagnosis. J Natl Cancer Inst. 2021;113:1131-5.doi:10.1093/jnci/djaa140. Medline

11. Porzsolt F, Matosevic R, Kaplan RM. Recommendations for cancer screening would be different if we measured endpoints that are valid, reliable, specific, and important to patients. Cancer Causes Control. 2020;31:705-11. doi:10.1007/s10552-020-01309-w. Medline

12. Zeng L, Helsingen LM, Kenji Nampo F, et al. How do cancer screening guidelines trade off benefits versus harms and burdens of screening? A systematic survey. BMJ Open. 2020;10:e038322. Medline

13. Stiggelbout A, Copp T, Jacklyn G, et al. Women’s acceptance of overdetection in breast cancer screening: can we assess harm-benefit tradeoffs? Med Decis Making. 2020;40:42-51. doi:10.1177/0272989X19886886. Medline

14. Zahl PH, Kalager M, Suhrke P, Nord E. Quality-of-life effects of screening mammography in Norway. Int J Cancer. 2020;146:2104-12.doi:10.1002/ijc.32539. Medline

15. Giard RWM, Hart W. De pretenties en prestaties van kankerscreening, in het bijzonder voor borstkanker . Ned Tijdschr Geneeskd. 2002;146:1045-9 Medline

Article by Y. van der Graaf
The hidden risks of screening

Yolanda van der Graaf


With screening, the natural course of the disease should be altered to reduce mortality from that disease. Screening offers minimal benefit but has many disadvantages, like false positives, overdiagnosis, and psychological distress. The advocates of screening overestimate the importance of the disease and the effects of screening but neglect the disadvantages. But also, potential participants and medical doctors overestimate the effects of screening. Although considered important, the still valuable criteria by Wilson and Jungner are neglected by researchers and committees that approve screening. Even when doctors disapprove of screening, healthy people are willing to undergo body scans, although nobody knows how to deal with the many abnormalities detected. Screening programmes should be evaluated against other interventions and not simply by making models with many unproven assumptions. And most of all, the potential participants must be informed about the possible disadvantages and the minor effects on health.

Detecting disease before it gives symptoms must be better, right? 'Prevention is better than cure.' That seems like such a simple premise that many people do not need any proof for it. But the reality is much more complex.
Why is screening so attractive to citizens, healthcare providers, industry, and government, and why are the disadvantages so hard to find? In this article, I describe the principles of screening, overestimation of the risk of disease by the society, and the unfamiliarity of doctors and participants with the real effects of screening on health.

I then quantify the risks of screening and discuss why screening nevertheless remains so popular.

The principles of screening

With a simple screening test, we try to classify people without symptoms into high-risk and low-risk groups. Almost always, a second test is needed - for example, a biopsy - to confirm the presence of disease. After confirmation, we start treating the disease. The goal of screening is to change the natural course of the disease favorably. But this assumes that we know what this natural course looks like and that there is a latent stage in which the disease can be detected and treated.
Sometimes we detect the disease earlier, but we are still too late, and the participant only lives longer with the awareness of the disease. And sometimes, we detect tumors that someone will never suffer from.
So in tumors detected by screening, we can find a more favorable prognosis than in tumors detected because they gave symptoms. On the one hand, this may be due to a biological difference between the tumors, known as length-time bias. On the other hand, some survival gain is artificial because we pick up tumors in screening earlier than if we wait until they give symptoms. This phenomenon is the "lead-time" bias. That length and lead-time bias evaluate screening complex, so only comparative studies, often with more than ten years of follow-up, provide a good picture of the advantages and disadvantages of screening.

Wilson and Jungner already thought more than 50 years ago that "earlier" can only be better if a number of conditions are met.1
Although these conditions are always mentioned in Health Council reports, you only have to compare the current cervical cancer screening with these criteria to see that there has been a serious lack of compliance (Table 1).  Cervical cancer is not a major public health problem, and there is a considerable discrepancy between the number of premalignant abnormalities detected and the number of women with invasive cancer. And because knowledge about the course of premalignant abnormalities is insufficient, there is widespread overtreatment.

It seems that with the upcoming legislation - the Preventive Medical Examination Act - the disadvantages of screening have already been brushed entirely under the carpet.2,3

Overestimating the risk of disease

In general, the risk of disease is quite overestimated. The Dutch Brain Foundation is trying to make us believe that. Dutch people has a brain disease.4 That seems like a lot until you read that 1.9 million Dutch people have a personality disorder, anxiety, or panic disorder. Sleeping badly suddenly turns out to be a brain disease. Even for cancer, the actual risk is overestimated.
Rarely is told what the 'lifetime' risk is of dying from cancer. Only 3% of women die from breast cancer. The chance of dying from colon cancer is 'only' 2%.
On the RIVM website, I read that 1 in 7 women will get breast cancer at some point in their lives. 5 That is irrelevant because most breast cancers do not kill women. Not even without screening. What matters is the risk of dying prematurely from breast cancer and how that risk is reduced by participating in screening. Moreover, the age at which one dies is an important fact lost when presented with the usual absolute numbers of a cancer type.

Overestimation of the impact of screening

Potential participants greatly overestimate the benefits of population screening. An extensive interview study with more than 10,000 participants that asked how much disease-specific mortality reduction population screening for breast and prostate cancer found that more than 92% of women overestimated the effects of screening by a factor of 10.6
In the Netherlands, more than 50% of women think that because of the screening program, more than 50 out of 1,000 women will no longer die of breast cancer. And 20% do not know. The correct answer: per 1000 women screened, 1 woman will die less from breast cancer. That answer was given by 1% of respondents.
Doctors also overestimate the effects of screening. 7 More than 50% of U.S. physicians were found not to understand the principles of screening. They thought that the higher number of tumors in the screened group was proof that screening is effective.
Three-quarters had never heard of lead-time bias. In a September 25, 2018, press release, Erasmus MC claimed that screening for lung cancer prevents thousands of deaths.8 The sobering numbers accompanying this optimism appeared a year later.9 But even if no medical profession sees the value of a screening test and there is not a shred of scientific evidence, people allow themselves to be screened.10 A good example of this is the so-called body scans that the commercial company Prescan which more than 150,000 clients have used since 2003.

The risks of screening are high

The effects of screening for cervical, breast, and colon cancer have been extensively studied. We know approximately the number of people who need to be screened to prevent 1 death from cancer in question. The main problem is that this is not adequately communicated to the potential screening participants. A much bigger problem is that of screening initiatives whose effectiveness is not even known, not to mention that there is an awareness of overdiagnosis and overtreatment.
For every death from breast cancer that you prevent with screening, 1000 women need to be screened regularly. Through a screening program, more than 100 women are treated unnecessarily .11,12 The odds of unnecessary treatment are thus dozens of times higher than that of a woman benefiting from screening. Recently, the percentage of women between 50-74 diagnosed with breast cancer by screening but who will never develop breast cancer was estimated at 15.4%.13

Why is a total body scan not useful?

Scans (CT and MRI) reveal much more than we would like. In particular, they map out aging. The potential benefit of the total body scan lies in the early detection of malignant tumors, vascular abnormalities, and calcifications. A priori, don't expect a body scan to be useful. For that, the prevalence of malignant tumors is too low; treating asymptomatic vasoconstrictions(carotid, coronary vessels) causes harm, and calcium in the coronary vessels may predict risk but does not mean that interventions are useful.16 Calcifications are simply a sum of the classic risk factors and interactions between genes and the environment. The big problem with the total body scan is the excessive amount of findings that no one knows how to deal with. A review of 15,877 patients showed the percentage of extracardiac results to be 44% (95%-BI: 35-54).17
A similar systematic review that included a total of 12,922 patients found the prevalence of clinically relevant findings was 13% (95%-BI: 9-18).18 The studies used a pragmatic definition of 'clinically relevant: findings that a clinician should look for (e.g., pulmonary embolus, cysts, larger nodules, lymphoma, suspicion of malignancy).
Characteristics that you would expect to influence prevalence, such as age, percentage of smokers, or field of view ("field of view"), were not explanations for the differences in prevalence. Probably because the definition of 'clinically relevant abnormality' is inconsistent.

But people's fear of cancer also generates a lot of money. 20 For convenience, no research is done on effectiveness; instead, recruiting claims are used. Under the guise that you will gain insight into your health in one day, people are seduced. For € 1250, you get 5 MRI scans - of the skull and brain, cervical vessels, chest, upper and lower abdomen - and laboratory tests. It's a great revenue model because the provider only does diagnostics. No follow-up research and no treatment. Prescan, a company that offers total body scans, throws the consequences of abnormal findings over the fence. The curative sector should take care of that.

Is screening worth the money?

Finally, a few words about the evaluation of screening: this evaluation compares screening with a situation where there is no screening. Such a comparison often lacks important data and uses complex models that almost no one can understand.

A long time ago, we decided that we were willing to pay €20,000 for a year of life saved, but today the question is, what else could we do with that money? Virtually all smoking cessation interventions are feasible for a significantly lower threshold value than the €20,000 per life year gained. By far, the most health gains can be achieved in the Netherlands regarding smoking cessation. These dwarf the health benefits of screening programmes.


Although screening has been practiced for decades, the disadvantages of screening are not adequately addressed. The reality is that 'earlier' is not always better. Proponents of screening cannot refrain from exaggerating the risk of serious disease, overestimating the benefits of screening, and ignoring large numbers of false positives.

The screening evaluation is currently deficient because it does not weigh whether much more health benefits can be achieved with the same costs but different efforts. Screening should be evaluated by independent scientists and not by people who have often been involved in screening for decades. In addition, the proliferation of screening programs for which there is not a shred of scientific evidence and for which financial gain is paramount should be vigorously opposed. But above all, participants in a screening program must be fairly informed. This journal made some very good suggestions for this back in 2009.

Online artikel en reageren op ntvg.nl/D6760
UMC Utrecht, Julius Centrum, Utrecht: prof.dr. Y. van der Graaf, klinisch epidemioloog.
Contact: Y. van der Graaf (y.vandergraaf@gmail.com)
Accepted on May 5 2022
Cited as: Ned Tijdschr Geneeskd. 2022;166:D6760


1. Wilson JMG, Jungner G. Principles and practice of screening for disease. Genève: WHO; 1968.

2. Krom A, Dekkers OM, Ploem MC. Verlies de nadelen van screening niet uit het oog: zorgen over wijziging Wet op het bevolkingsonderzoek. Ned Tijdschr Geneeskd. 2022;166:D6701.

3. Wijziging van de Wet op het bevolkingsonderzoek in verband met actuele ontwikkelingen op het terrein van preventief gezondheidsonderzoek. Tweede Kamer der Staten-Generaal. Kamerstuk 35384.

4. Een op vier Nederlanders heeft een hersenaandoening. RIVM, 27 november 2017. www.rivm.nl/nieuws/op-vier-nederlanders-heefthersenaandoening, geraadpleegd op 1 juni 2022.

5. Bevolkingsonderzoek borstkanker. RIVM, 19 april 2022. www.rivm.nl/bevolkingsonderzoek-borstkanker, geraadpleegd op 1 juni 2022.

6. Gigerenzer G, Mata J, Frank R. Public knowledge of benefits of breast and prostate cancer screening in Europe. J Natl Cancer Inst. 2009;101:1216-20. doi:10.1093/jnci/djp237. Medline

7. Klemperer D. Physicians’ and patients’ knowledge of cancer screening - a wake-up call. Oncol Res Treat. 2014;37(Suppl 3):8-10. doi:10.1159/000363459. Medline

8. De Visser E. Screening op longkanker bij bij (ex-)rokers zou ‘duizenden doden voorkomen’, maar deskundigen zijn sceptisch. de Volkskrant, 26 september 2019.

9. De Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.N Engl J Med. 2020;382:503-13. doi:10.1056/NEJMoa1911793. Medline

10. Nederlandse Vereniging voor Radiologie. Standpunt NVvR screenende total body scans / health checks. www.radiologen.nl/nvvr/standpunt-nvvr-screenende-total-body-scans-health-checks, geraadpleegd op 1 juni 2022.

11. Zaat J. Minister, ik wil een bevolkingsonderzoek. Ned Tijdschr Geneeskd. 2018;162:C4055.

12. Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2013;(6):CD001877 Medline.

13. Ryser MD, Lange J, Inoue LYT, et al. Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort. Ann Intern Med.2022;175:471-8 (epub ahead of print). doi:10.7326/M21-3577. Medline

14. Vermeer NC, Liefers GJ, van der Hoop AG, Peeters KC. Bevolkingsonderzoek naar darmkanker: zucht of zegen? Ned Tijdschr Geneeskd. 2015;159:A9059.

15. Factsheet bevolkingsonderzoek darmkanker. RIVM, 11 december 2020. www.rivm.nl/documenten/factsheet-bevolkingsonderzoekdarmkanker,geraadpleegd op 1 juni 2022.

16. Sedlis SP, Hartigan PM, Teo KK, et al; COURAGE Trial Investigators. Effect of PCI on long-term survival in patients with stable ischemic heart disease. N Engl J Med. 2015;373:1937-46. doi:10.1056/NEJMoa1505532. Medline

17. Flor N, Di Leo G, Squarza SA, et al. Malignant incidental extracardiac findings on cardiac CT: systematic review and meta-analysis. AJRAm J Roentgenol. 2013;201:555-64. doi:10.2214/AJR.12.10306. Medline

18. Buckens CF, Verkooijen HM, Gondrie MJ, Jairam P, Mali WP, van der Graaf Y. Unrequested findings on cardiac computed

tomography: looking beyond the heart. PLoS One. 2012;7:e32184. doi:10.1371/journal.pone.0032184. Medline

19. Johansson M, Borys F, Peterson H, Bilamour G, Bruschettini M, Jørgensen KJ. Addressing harms of screening - A review of outcomes in Cochrane reviews and suggestions for next steps. J Clin Epidemiol. 2021;129:68-73. doi:10.1016/j.jclinepi.2020.09.030. Medline

20. In één dag inzicht in je gezondheid! Prescan. www.prescan.nl/?gclid=Cj0KCQiA9OiPBhCOARIsAI0y71AT0HHRx4u4UkvG5luXgrTUZBmKGxdbdMTrZ8Q6maDE2NGV3PYvVIEaAqhYEALw_wcB, geraadpleegd op 1 juni 2022.

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.

Potential benefits, as well as harms, from the COVID-19 disruption on cancer screening

May, 28th

Online early publication https://doi.org/10.17061/phrp32122208

During the Covid pandemic, some scientists and journalists from various fields predicted that disruptions in cancer screening programs would result in a "tsunami" of advanced breast, prostate, colon, and cervical cancers and deaths.

This prediction is strongly challenged by several scientists in this April 27 publication by Australian authors, who even consider the period of screening cessation as a "natural experiment" to finally accurately assess the benefits and harms of routine health care.

In some cases, it may be possible to identify where healthcare costs can be cut, particularly for low-value-added healthcare devices, because these decreases during the pandemic were not harmful or even beneficial.

Both short-term and long-term consequences must be evaluated.

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.

Update on Tomosynthesis

May 17, 2022

Article in Auntminnie

Reminder: Tomosynthesis (or 3D mammography) is a radiological imaging technique that reduces the effect of superimposition of breast tissue as it reconstructs a three-dimensional image of the breast from several low-dose X-rays acquired from different projection angles.

This technique was heavily promoted about 10 years ago. Therefore, a review is done after 10 years of hindsight in the media "AuntMinnie.com."

This is a community website for radiologists and professionals in the medical imaging industry. According to this rather collaborative media that connects radiologists, business managers, and industry professionals to "meet, do transactions, research and collaborate," tomosynthesis has clearly disappointed.

Many questions and doubts about the benefit of using this technique have been raised previously:  https://pubmed.ncbi.nlm.nih.gov/30816931/

- tomosynthesis does not reduce false alarms
- the additional use of tomosynthesis does not reduce interval cancers
- tomosynthesis would increase overdiagnosis
- the benefits of tomosynthesis are not clear

1° Cancer detection

Digital mammography alone has been compared with digital mammography + tomosynthesis (a higher-radiation combination): matched studies* have shown that the addition of tomosynthesis made it possible to find more cancers: 8.8 per 1000 women compared with 6.4 per 1000. But in other unmatched studies*, the difference was narrower, 5.7 cancers detected per 1000 women versus 4.5.

* Matching consists of setting up pairs (1 case and 1 control) with the same characteristics (e.g., age) to compare the results while avoiding potential confounding factors. The groups are thus "balanced" on these characteristics.

2° Recall rates

What about recall rates? The recall rate refers to false alarms during screening, i.e., suspicions of cancer that will not be confirmed, but only after recalling the patients who will need to have other complementary explorations before deciding on these suspicions. Here again, the data vary according to the study conducted.

Based on the March 2022 study summarized here, repeated breast cancer screening with 3D mammography only modestly decreases the risk of having a false-positive result compared with standard digital mammography.

What can we learn from this study?

The risk of a false-positive result was lower when screening was performed every two years instead of every year and in the case of non-dense breasts and older women.
However, the difference was modest, and the reduction in false positives by using 3D mammography was only 2.4% compared to standard mammography.

3°How effective are synthetic mammography images?

In 2012 an opening was made for 'synthetic imaging,' which records a single radiological acquisition and therefore delivers a single dose of radiation, thus avoiding the over-irradiation caused by 3D mammography**.

But are the synthesized images an effective alternative to digital mammography images? Clinical results of effectiveness tests of synthesized mammographic images are unfortunately mitigated. Overall, the results between synthesized images are equivalent to digital mammography, although the latter has a better resolution.

**Classically, 2D mammography and 3D tomosynthesis acquisitions are used in combination. This results in a significant increase in the X-ray dose delivered. The X-ray doses delivered by combining 2D mammography and tomosynthesis are about twice the dose of 2D mammography alone.
Synthetic 2D tomosynthesis is an alternative, obtained by reconstruction from 3D acquisitions only; it avoids the joint use of 2D mammography and thus reduces the delivered dose.

4° Does tomosynthesis reduce mortality?

Does tomosynthesis result in a reduction in mortality? According to this article in Autminnie.com, a survey of eight studies conducted between 2016 and 2021 investigated whether tomosynthesis reduces rates of interval cancers (cancers not caught by screening because they occur between two mammograms) compared with digital mammography alone. Interval cancers are often very aggressive and occur quickly, thus missed by screening. They are correlated with mortality because their intrinsic aggressiveness endangers the survival of women, often because of their metastatic potential.

It was found that tomosynthesis does not impact the rate of interval cancer.

In conclusion

Ten years after its use, the benefits of tomosynthesis may be much more modest than clinicians initially expected. In conclusion, this technique is finally similar to digital mammography with no proven advantage.

Even if the detection rate of tomosynthesis seems slightly better, the benefit of this technique remains an open question. If this moderate improvement in cancer detection is gained at the cost of increased overdiagnosis, we cannot conclude that the benefit/risk ratio is favorable.

As usual, the major concern is the information provided to women, as tomosynthesis is sometimes performed in radiology offices without the knowledge of the patient who comes for a routine mammogram, who does not benefit from it and is exposed to unnecessary over-irradiation.

Also read: https://www.bmj.com/content/366/bmj.l4506

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.

When marketing, finance, lobbying, and advertising invite themselves into the health care sector

Commercial determinants of cancer control policy (Eurohealth)

European Observatory on Health Systems and Policies (downloadable)

27 April 2022, Journal article
Summary by Dr. Cécile Bour - 30 April 2022

In this Eurohealth report, the authors focus on the negative influence of private interests on prevention, screening, and healthcare policies.

Cancer control, as defined by WHO and also often referred to as "cancer prevention and care," consists of a continuum from prevention, early detection (i.e., screening and early/rapid diagnosis of symptomatic patients), diagnosis, and treatment, to palliative/supportive care and survivorship

A definition of "the commercial determinants of health" was presented to the United Nations (UN) General Assembly 2017: "The commercial determinants of health are those conditions, actions, and omissions that affect health. Commercial determinants arise in the context of the provision of goods or services for payment and include commercial activities, as well as the environment in which commerce takes place.
Generally, private sector activities that impact population health."
This issue of the commercial determinants of cancer, referred to as the "dark side of health," has not yet been thoroughly explored.

According to the World Health Organization (WHO), 30-50% of all cancer cases are preventable, with tobacco use being the leading preventable cause of cancer in Europe. Other important risk factors are alcohol consumption, overweight and obesity, poor diet, and insufficient physical activity.
Added to this are sources of radiation and other chemical carcinogens, including from the cosmetics industry. These sources also increase the risk of developing various forms of cancer.

Europe is one of the largest markets for alcohol sales and is also the region with the highest proportion of alcohol-related diseases and premature mortality.
Europe has the highest average current tobacco use among adolescents. The evidence for a causal link to cancer is indisputable.
Of course, various behavioral and environmental factors account for the increased incidence of cancer. Many are preventable, but corporate interests and actions undermine public health efforts to combat them.

The response to industry criticism takes many forms. It ranges from threats of legal action for infringement of the industry's commercial rights, including intellectual property and economic freedom, to concerns that constraints on the industry will have a disproportionate impact on the economy and employment.
Other examples of industry tactics include enhancing corporate reputation (the concept of corporate social responsibility (CSR)*), denying the impact of their products or diverting attention from the harms caused by their products, and attempts to build an "evidence" base and then divide the public health community.
The bottom line is that the impact of tobacco and alcohol industry players on the cancer continuum includes a range of effective tactics that undermine public health, including recent direct marketing** to consumers.

* Companies consider environmental, social, economic, and ethical issues in their activities.

** Direct marketing is a communication and sales technique that consists in broadcasting a personalized and inciting message to directly reach a target of individuals to obtain an immediate and tangible reaction.

Deceptive drifts

A-Innovation as a panacea

It is striking that most of the articles reviewed in this report raise a particular concern, namely a blind and deceptive faith in "innovation."

Innovation has great appeal to policymakers, clinicians, the public, and donors, but all authors caution against launching new preventive, diagnostic, or therapeutic innovations without a rigorous evaluation of their basic safety and benefit to the population and call for an adequate evidence base to demonstrate their effectiveness and cost-effectiveness.
They also remind us of the rapid growth in pharmaceutical revenues generated by the sale of cancer drugs, despite a lack of return in terms of survival or cure during the same growth period.

B- Screening

The Council of the European Union still recommends screening for cervical, breast, and colorectal cancers, but with more nuanced information, and has published a guide to the proper use of systematic screening.

Since then, research continues to evaluate the advantages and disadvantages of screening, particularly for other types of cancers (lung is under study).

Despite an evidence base that does not support such practices, much "opportunistic" (i.e., off-recommendation, requested by a public demanding more medical care) screening occurs across Europe.
Managers and sales representatives play an essential role in promoting systematic testing practices that can do more harm than good (see the massive sponsorship at Pink October).
Commercial drivers can work through financial incentives, creating a "culture" that promotes rapid adoption of new technologies, lobbying, and marketing to clinicians and consumers.

The report says that many people may be included in irrelevant screenings, and resources may be diverted from those most in need of medical attention and treatment.
Overdiagnosis, in particular, is currently a specific problem. Since, at the individual level, it is not possible to determine whether cancer will progress or not, healthy people may be subjected to potentially unnecessary diagnostic procedures and treatment, with a consequent risk of adverse effects.

For example, thyroid screening has no benefit for the population but provides considerable evidence of massive overdiagnosis and unnecessary therapeutic procedures.

The first wave of cancer screening tests was developed mainly in the public sector and promoted by charities and professional bodies. There is a new wave of innovation in cancer screening, and much of this innovation comes from the private sector, often supported by professionals.

Diagnostic companies have become essential players in promoting new screening technologies, private laboratories and clinics may seek to expand the market for screening services by offering new technologies (such as 3D mammography) or expanding into disease areas not covered by national programs, which could increase public demand and intensify political pressure for their adoption within public health systems.

There has been a lot of commercial enthusiasm for cancer screening (such as predictive software, see for example here and here), industry analysts predicting the potential for "drug-like blockbuster revenues."

Companies developing new cancer screening technologies based on liquid biopsy have attracted huge billions of dollars in private investment. The technology has been very disappointing in screening, clinical studies that lack the rigor to assess the harms and benefits of this technology fully and accurately have been published to great media hype, and a phenomenon of "capture" of key opinion leaders has been added, through research collaboration with industry.

There is evidence, according to the report, that the new generation of molecular testing is being marketed using strategies that come directly from the pharmaceutical industry: recruitment of key opinion leaders, direct-to-consumer advertising, direct-to-physician advertising, and funding of NGOs, including patient organizations, to engage in ostensibly independent lobbying for government adoption of new technologies.
The commercial drive to generate revenue leads to distorted messages that present a partial view of the scientific evidence, biased towards claimed health benefits but obscuring potential harms, resulting in unnecessary public expenditure.
Carefully crafted public relations strategies can ensure media coverage that reinforces this unbalanced image, such as liquid biopsy molecular tests, 3D mammography, and artificial intelligence-based detection, which are heavily geared toward declaring tremendous benefits to populations and generally fail to report conflicts of interest.


Da Vinci Robot: this device is put forward in the report as the archetype of NPT (non-pharmaceutical technology).

Few technologies better represent the commercialization of the so-called NPT than the Da Vinci Robotic Surgical System.
This device, which allows surgeons to perform surgery remotely, sitting at a console to operate remote-controlled arms for micro-invasive surgery, was first approved by the U.S. Food and Drug Administration (FDA) in 2000.
Despite the lack of clear evidence of its superiority over open and laparoscopic techniques and its enormous costs, the method has been widely adopted throughout Europe, even in countries with lower living standards. Its inherent benefits, including improved visualization of the surgical field, greater range of motion of the robotic arms, and improved ergonomics for the surgeon, were expected to translate into improved patient outcomes. However, in the case of prostate and rectal cancer, no improvement in functional or oncologic outcomes was observed.

This is even though guidelines have been created to improve the rigor of evidence collection, particularly for medical devices.
Regulatory approval of a new medical device or technology requires clinical data and a demonstration of its safety before bringing the device to market.
In comparison, systemic therapies must go through a more complex process of demonstrating efficacy beyond current standards of care. This partly explains the lack of randomized controlled trials for medical devices.

However, the recent Cumberledge review highlighted the devastating impact of integrating drugs and devices without rigorous and thorough evaluation of the implications for patients, especially in terms of safety and health benefits. Unfortunately, the design of studies used to evaluate new technologies often lacks rigor. However, it can form the basis for clinical implementation, with less reliable single-center retrospective series still dominating the literature.

D-Lack of balanced media coverage

This drift can influence public perceptions and those who make decisions about funding biomedical research and clinical care, exacerbating general support.

We refer here to the enormous enthusiasm for innovation and, in particular, the idea of personalized or precision medicine, rooted in the long-standing belief that genomics will revolutionize the practice of medicine, a view now reinforced by faith in the transformative potential of digital technologies, including artificial intelligence

Public policymakers are prone to this form of buy-in, which can have two potential adverse effects on public health, including:

- a willingness to adopt new technologies because they are believed to represent the future of health care, without solid evidence that they improve clinical outcomes;

- misallocation of research resources, as funding goes to the discovery and development of new technologies, at the expense of simpler incremental improvements in care delivery, such as improved rapid clinical diagnosis for patients with actual potential symptoms of cancer

This can be a waste of resources, but in countries that lack qualified technicians in areas such as imaging or endoscopy, it exacerbates these shortages and delays in diagnosis for symptomatic individuals. It also exacerbates growing inequalities in access to medical care.

The landscape of commercial screening offerings is being transformed by innovation in diagnostic technologies and the broader development of the Internet as a new mechanism for consuming health care. In recent years, various consumer biological testing services sold over the Internet have been the subject of regulatory action.

In conclusion, and as Ioannides noted, medicine and health care waste society's resources because "we" as clinicians have allowed evidence-based medicine in cancer to be diverted by using technologies with marginal effectiveness but maximum cost.

The commercial determinants of cancer remind us that both governmental and whole-of-government approaches (combining vertical and horizontal management while partnering with organizations outside of government) are essential to meeting the challenge facing our society and that health decisions remain a political choice.

Range of ways in which private interests influence public health

1. Financial incentives affect all areas of health

- Economic incentives are misaligned with the promotion of overall quality of life.

- There is a misrepresentation of clinical information and public health data. (For example, in breast cancer, read here and here)

Economic incentives drive the development of new drugs with increasing applications, leading to trials over weak comparators (e.g., non-inferiority studies) and approvals based on modest effects in new settings.
In discussing the development of new screening technologies, diagnostic tools using molecular biomarkers, new precision therapies, or targeted drugs, all authors of the WHO report raised concerns about whether a drug or device efficacy measures were validated correctly.
Measures of benefits may or may not track in parallel outcomes that matter to patients, such as data on reduction in overall (all-cause) mortality or parameters such as quality of life; several of the report's authors expressed concern about how social factors and economic incentives have shaped clinical care, advertising, and investments in ways that do not promote the health and well-being of patients overall.

2° Lobbying

On behalf of the industry, and with the complicity of physicians and opinion leaders, the promotion of cancer screening research and technology development has led to an overemphasis on the benefits of these tools and technologies. It underestimates the harms of false positives or overdiagnosis.

3. Advertising

Many authors have drawn attention to the misleading nature of advertising and media communication about cancer risks and treatments.

They have raised concerns about the overselling of cancer drugs and new and unproven technologies.

4° Economic factors

Economic factors influence the rising costs of care, which disproportionately affect the most disadvantaged. For example, the uncritical press for new drugs and "technomania" has contributed to the increasing costs of new drugs and screening technologies, making access to care even more difficult for many patients, particularly those in developing countries.

Regulatory tools could encourage investment in actual prevention measures (alcohol, tobacco, obesity, physical inactivity), better palliative care, and more integrative care.

There is also a need for improved medical education on the roles of commercial interests in shaping cancer care, which may already mitigate tendencies toward "technomania" among physicians so that medical students have a better appreciation of the costs and benefits of new treatments and technologies, as well as the importance of palliative and end-of-life care with better patient integration.

How can we do better?

In summary, there are ethical and justice issues everywhere, and these issues have to do with respect for patient autonomy, equity, and beneficence.
Autonomy, with strong patient support and transparent communication about the benefit-risk balances of health devices.
Equity and justice about risk identification and prevention, early detection, alternative solutions, therapeutic solutions, and palliative care appropriate to the patient's real need.

Regulatory tools need to be developed to improve medical education, emphasizing transparency. Public administrations, national governments, and international agencies can do, and civil society can demand to mitigate the harms associated with conflicts of interest.

The authors also note a clear need for high standards, both at the level of the European Medicines Agency and through more robust health technology assessment mechanisms, with more sophisticated pricing and reimbursement systems at the national level.

The inadequate quality of research and regulatory standards and the critical lack of correlation between economic incentives and what is sought in terms of overall patient quality of life is a critical issue.

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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Cancer Screening—The Good, the Bad, and the Ugly

JAMA Surg. Published online April 6, 2022. doi:10.1001/jamasurg.2022.0669

H. GilbertWelch,MD, MPH-Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, Massachusetts.

In clinical practice to say that a person has cancer gives as little information about the possible course of his disease as to say that he has an infection. There are dangerous infections that may be fatal and there are harmless infections that are self-limited or may disappear. The same is true of cancers. Cancer is not a single entity. It is a broad spectrum of diseases related to each other only in name. George Crile,MD, cancer surgeon 1 (p128)

Dr Crile’s recognition of the heterogeneity of cancer growth

Dr Crile's recognition of the heterogeneity of cancer growth in a 1955 issue of LIFE magazine presaged why early cancer detection might defy simple intuition. It is tempting to think that cancer screening can only help individuals and that all survivors of cancer detected by screening provide powerful evidence that it saves lives. However, cancer screening is counterintuitive. It turns out that the harms are more certain than the benefits; the survivors are less likely to be evidence of its benefit and more likely to be evidence of its harms.

Dr Criles uses an analogy of a barnyard pen :

The bird is a very fast cancer (missed by screening). The bear is a slow cancer, caught by the screening but which, not screened, would have manifested itself just a little later by a clinical symptom without loss of chance. The turtle and the snail represent very slow and stagnant cancers, for which screening is useless, because they would never have manifested. The patient dies with her cancer but not because of it.
The birds have already escaped the barnyard: they are the fastest growing and most aggressive cancers, those that have already spread by the time they are detectable. Screening cannot help with the birds.

Editor's note, another representation:

Limited (or Uncertain) Benefit

The goal of cancer screening is to reduce cancer mortality. Screening tends to miss the fastest growing cancers (the birds) because these cancers have such a short time window during which they are detectable by screening, but they are not clinically evident. Furthermore, effective screening requires not only earlier detection, but also treatment initiated earlier is reliably better than treatment initiated later.
Now we can notice that as cancer treatment improves, the benefit of screening decays. If clinically detected cancer can be routinely treated successfully, the utility of cancer screening naturally falls to zero.

Poorly Recognized (or Hidden) Harms

From an individual’s perspective, overdiagnosis is the most consequential harm of screening.
Overdiagnosis is so rarely confirmed in an individual (ie, a patient with a cancer that is detected by screening but is not treated, never develops symptoms, and dies of some other cause), so there was considerable debate about whether the problem really existed.
However, overdiagnosis can be easily confirmed at the population level. Thus, debates about the existence of overdiagnosis are now largely settled and have rightly moved to the question about its frequency— and how much it matters. In the case of breast, prostate, skin, and thyroid cancer screening, patients are more likely to experience the harm of overdiagnosis than they are the benefit of screening—avoiding a cancer death.

Problem is: many individuals must be screened to potentially benefit a very few. Roughly 1000 people must be screened to avert 1 cancer death in 10years.2 Thus, questions about what happens to the other 999 individuals become relevant.

Another issue apart from overdiagnosis: false alarms affect many: there are as many as 600false-positive results in a 10-year course of mammography.3 However, the bigger problem is that many people with false-positive test results are not told that the test was wrong, but rather that something is wrong with them.

Misleading Feedback, Financial Incentives, and Distraction

These harms might be acceptable were they accompanied by substantial and certain benefit. Unfortunately, screening itself provides misleading feedback that always suggests it is more beneficial than it really is.

As shown in the example in panel B of the Figure, the proportion of late-stage cancers detected falls from 50% to 25%, despite no change in late-stage incidence. Over time, 5-year survival rises owing to the combined association of lead time and overdiagnosis bias, even if the age of death is unchanged. Survivor stories are particularly pernicious: the more overdiagnosis from screening, the more people there are who believe that they owe their life to the test—and the more popular screening becomes.4 (click on the picture below)

Editor's note: In fact, if overdiagnosis could be completely eliminated, the proportion of advanced cancers would appear to be greater in the total number of cancers minus overdiagnosis, which usually amplifies the total number of cancers. The proportion of advanced cancers is diluted in the total cancer count when the proportion of overdiagnoses is added to this total. See the screening paradox:

Pr Welsch's conclusion

Dr Crile believed that medical care should be driven by patient needs, not surgeon needs (or now, system needs). He recognized there was a price to be paid for getting ahead of symptoms. Although cancer screening may make sense in selected high-risk individuals, I believe general population screening, as currently practiced in the US, has become a huge distraction to our core work.  It distracts the system away from acutely ill and injured patients: as physician performance is measured in terms of how frequently they test the well and not how well they care for the sick. General population screening distracts patients and policymakers away from the genuine determinants of human health. The tremendous resources involved in screening—in terms of money, people, and effort— would be better directed elsewhere.


1. Crile G Jr. A plea against blind fear of cancer. Life. 1955;128-142.

2. Welch HG. Evidence on cancer screening efficacy in randomized trials & effectiveness in US practice. Accessed March 2, 2022.

3. Hubbard RA, Kerlikowske K, Flowers CI, Yankaskas BC, ZhuW, Miglioretti DL. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011;155(8):481-492. doi:10.7326/0003-4819-155-8- 201110180-00004

4. Raffle AE, Gray JM. Screening: Evidence and Practice. 2nd ed. Oxford University Press; 2019.

Read more: https://cancer-rose.fr/en/2020/12/17/are-small-breast-cancers-good-because-they-are-small-or-small-because-they-are-good/

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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