The irreversibility of screening

Dr. C.Bour, September 26, 2022

A short history

Whether useful or not, introducing screening into the population is irreversible. This is demonstrated by history.

1° Prostate cancer screening

The American doctor who developed the test in 1970, Richard Albin, was himself alarmed by the "public health disaster" caused by his discovery. In an op-ed published in the New York Times in 2010, he wrote: "I could never have imagined, four decades earlier, that my discovery would cause such a public health disaster, driven by the pursuit of profit. The improper use of this dosage must be stopped. It would save billions of dollars and millions of men from unnecessary and mutilating treatments."

PSA testing has been controversial since 1989 in France. A "consensus conference" was organized by three urologists, Professors François Richard, Guy Vallancien, Yves Lanson, and the economist Laurent Alexandre. This expert consultation already concluded that "the organization of mass screening for prostate cancer is not recommended.”
A new consensus conference was held in 1998. The same year a clinical practice recommendation was issued that ruled even more clearly: "Since screening for prostate cancer (whether mass screening, directed at the entire population concerned or opportunistic screening, on a case-by-case approach) is not recommended in the current state of knowledge, so there is no indication for proposing a PSA test in this context.

But things are not that simple. The majority of learned societies and professional groups around the world are against screening. Still, three American associations (American Cancer Society, American Urological Society, and American College of Radiology) do not agree. Gradually, the French Association of Urology (AFU) (specialists in the male reproductive system) is gradually drifting away from this position, and a campaign is being launched to promote PSA testing.

The problem with this screening lies in the fact that there is no established effect on mortality, but that, on the other hand, it detects a large number of very slowly progressing cancers that would never have been manifested (overdiagnosis), but which, once detected, will be treated, with disastrous effects in terms of impotence and incontinence.
Another problem is that radiotherapy treatments can lead to the development of secondary cancers.

In 2011, the US Preventive Service Task Force (USPSTF) recommended that PSA screening for prostate cancer be discontinued, emphasizing its side effects. For every 1000 people treated, there are 5 premature deaths one month after surgery. Between 10 and 70 patients have serious complications but survive. Radiation therapy and surgery have long-term effects, and 200 to 300 patients will become impotent and/or incontinent.

And the French High Authority for Health (HAS) concluded, "No new scientific evidence is likely to justify re-evaluating the appropriateness of implementing a systematic screening program for prostate cancer by PSA testing." Opinion renewed in 2016: 2016 HAS opinion
"The French National Authority for Health thus recalls that current knowledge does not allow for the recommendation of systematic screening for prostate cancer by PSA testing in the general population or in populations of men considered to be at higher risk."
The National Cancer Institute's conclusion is along the same lines.

Unfortunately, the recommendations and day-to-day practice are making a big gap, and biopsies, as denounced in 2013, are increasing.

Prescription habits have a hard time, but credit insurers also impose this test in the "formalities" requested to take out a loan, exposing people to seriously harmful effects on their health.

2° breast cancer screening

From 1970 to 1980, in various countries (Norway, Denmark, Canada, New York, Sweden), women were included in experimental studies, called trials, which simply compared the outcome for screened women with unscreened women. At the time, this was possible because the women had never x-ray taken on their breasts. These studies showed a supposedly tremendous reduction in mortality due to screening, up to 30% less risk of dying of breast cancer.

However, as we now know, these first experiments were subject to numerous biases in the method, the distribution of women between the two groups, and the statistical analyses. The methodology did not meet the current qualification criteria. The best results were obtained with the worst mammograms.

From 1992 to 2000, the number of victorious and enthusiastic publications multiplied with a colossal media echo.

Finally, from 2000 to 2001, voices were raised to warn about the irregularities of the first trials and to raise the alarm about the risks of this screening.

Peter Gøtzsche and Ole Olsen, two independent Nordic researchers, performed a meta-analysis according to the methodology of the Cochrane collaboration to which they belong. And there is a shock because even by combining the best trials, there appears to be no statistically significant difference in mortality between screened and unscreened women: "there is no reliable evidence that screening decreases breast cancer mortality," concludes the study [1].
This conclusion was later confirmed by the independent journal Prescrire in 2006 [2].

Unfortunately, these researchers were not allowed to publish their results in the Cochrane reviews, except on the condition that they would include even the most biased trials to improve the results.

Lengthy negotiations followed, and in 2009, researchers Peter Gøtzsche and Margrethe Nielsen estimated that if all the trials, including the worst ones, were included in the meta-analysis, then screening could reduce breast cancer mortality by 15%, which is still a minimal and supposed benefit [3].
Above all, a surprise “guest” emerges, and that is overdiagnosis, i.e., the detection of indolent lesions, unnecessary to detect, which would never have had an impact on the life or health of the woman, but which will all be treated like any other cancer, with surgery, radiotherapy, or even chemotherapy, leading to deleterious overtreatment for the person. These over-treatments have physical, psychological, economic (loss of job), trans-generational (descendants labeled as 'at risk'), etc., consequences.

In 2005, Norwegian statistician Per-Henrik Zahl, a member of the Cochrane Collaboration, raised the problem of discrepancies between studies showing a decrease in mortality and data from the official Swedish cancer registry. There would be more reported deaths in the unscreened group and missing deaths in the screened group. The researcher proposed an article on these discrepancies to the medical journal The Lancet, which was rejected.

One year later, Per-Henrik Zahl managed to have it published online in the European Journal of Cancer [4]. This article was censored and was finally published in a Danish journal shortly afterward [5].

In The Lancet, Peter Gøtzsche, co-founder of the Cochrane Collaboration, denounced the unacceptable pressure he had been subjected to [6].

But the machine had been launched, and European countries had started campaigns with much media coverage, with slogans, celebrity endorsements, and popular events colored in pink. And the press, as well as the learned societies, the women largely influenced by the media, the doctors, the health authorities, preferred to stick to the enchanting story of a screening that saves...

In 2004, under the presidency of Jacques Chirac, breast cancer screening was generalized in France.

In 2015/2016, under the aegis of Health Minister Mrs. Marisol Touraine, a citizen and scientific consultation on breast cancer screening was organized. The steering committee proposed two scenarios in the final report, both calling for the cessation of breast cancer screening in its current form because of a very uncertain balance of benefits and risks, with a non-significant reduction in mortality and, in parallel important adverse effects, such as irradiation, false alarms (see video at the bottom of this link) leading to stressful complementary examinations, and overdiagnosis of course. The citizens request better information.

Nowadays, screening is still conducted in its usual form, and women receive information on the benefit-risk balance that is still unclear and obviously unbalanced[7][8].

The scientific controversy about this screening is qualified as fake news by the National Cancer Institute[9].

3-Bronchopulmonary cancer screening.

Two trials essentially (there were several studies) were supposed to provide evidence of a significant reduction in specific mortality from bronchopulmonary cancer due to low-dose radiation thoracic scanner (LDRT) screening. These were the US National Lung Screening Trial (NLST) and the NELSON trial conducted in Belgium and the Netherlands.

Already in 2014, in a scoping note, the HAS noted, ".... it is likely that the low specificity of low-dose CT screening will remain a major obstacle to the implementation of screening in clinical practice and a screening program."
"Disadvantages and risks associated with FD CT (low-dose CT) screening include radiation exposure ranging from 0.61 to 1.5 mSv, some degree of overdiagnosis that varies among studies, and a high rate of false-positive exams, usually explored with more imaging."

When we look at the study published in the NEJM on the NELSON trial, the last line of table n°4 reads: "All-cause mortality - deaths per 1000 person-yr 13.93 (screening group) 13.76 (control group) RR 1.01 (0.92-1.11)". Clearly, there is no impact on all-cause mortality by this scan screening. (Remember that the "overall mortality" figure includes everything, cancer, its treatment, and its non-treatment, and is, therefore, a better reflection of "real life" data)

But the Academy of Medicine has retained this criterion and expresses its concerns in a published report here and there. It notes several problems for not generalizing this screening:

  • The two major lung cancer screening trials with low-dose CT scans greatly underestimated the potential harms (false positives, overdiagnosis, false negatives, radiation, and overtreatment). The magnitude of the benefit and the magnitude of the risks are unknown, and even if the 25% cure rate is achieved among the subjects included in the study, the majority of patients will die early from other smoking-related diseases (other cancers, heart disease, emphysema, etc.) without increasing their life expectancy.
  • For screening to be effective, it is necessary to have cancers with a sufficiently long latency to "catch up" during a screening (thus the least possible number of interval cancers); however, the proportion of long latency cancers in the lung is low.
  • These cancers are mostly due to active smoking and, marginally, to passive smoking: more than 85% of cases can be attributed to smoking. The progressive decrease of smoking among men (60% of smokers in the 60s to 33% today) is reflected in the reduction of incidence and mortality due to these cancers", which is equivalent to saying that this cancer is simply accessible to good primary prevention campaigns, and to incentives to stop the main risk factor, tobacco.
    "The natural and progressive history of the disease must be known and the various forms defined." Between the ages of 50 and 74, lung cancers are mainly composed of adenocarcinomas, which seem to be the most easily detectable. For example, in the European NELSON trial, 61% of PBCs in the screened group were adenocarcinomas compared to 44% in the control group, which could explain a better effect of screening in women", explains the Academy.
  • Unknowns: on the target population, the desirable participation rate, the frequency of scans, the therapeutic indications for cancers discovered during the scan, the acceptability by patients, the motivation and the respect of smoking cessation, etc...
  • The people who participate in the trials are not representative of the entire population eligible for screening at a later date, which may lead to an overestimation of the effectiveness in the Nelson study.
  • An economic evaluation is also needed, as the Academy rightly points out that primary prevention is certainly more effective and less costly.

To rebound on the arguments of the Academy of Medicine, one must keep in mind the economic stakes of this screening, not only of the initial examination but also of the importance of the expenses caused by the iterative examinations in case of intermediate nodules (which must be followed during the years to control their evolution). Screening for bronchial cancer by CT would be 4 times more expensive than screening for breast cancer and 10 times more costly than screening for colorectal cancer.

For academics, what is essential is the fight against the main risk factor: smoking, the acceptance of its reduction is the very condition for the candidates selected for a possible regular screening.

The reactions were not long in coming. An APM news release of February 24, 2021, tells us three learned societies have taken a position.
"The three learned societies are the Francophone Intergroup of Thoracic Oncology, the Society of Pneumology in the French Language, and the Society of Thoracic Imaging. In this text, which updates previous recommendations, the learned societies reaffirm their position in favor of individual screening, by low-dose thoracic CT scan without injection of contrast medium, for which they specify the modalities." ......
"Contrary to the French Academy of Medicine, which proposes a low-dose CT scan once during a smoker's health check-up, the learned societies envisage a recurrent examination. They believe 2 CT scans should be performed one year apart and then one every 2 years, except for risk factors or previous examinations with an intermediate result, which should continue every year. And this screening should be continued "for a minimum period of at least 5.5 to 10 years."

Three radiologists contest the opinion of the Academy of Medicine, which persists and signs: https://lequotidiendumedecin.fr/specialites/cancerologie/controverse-sur-le-depistage-du-cancer-du-poumon-lacademie-de-medecine-repond-aux-prs-revel-lederlin... with an argument that should prevail in any screening: namely that of the GLOBAL mortality.
"The authors mention that PBC (bronchopulmonary cancer) mortality is reduced in the Nelson and NLST trials, but without taking into account the general mortality of the smoking population, the only important parameter to consider organized screening and which does not change in the various trials."
This parameter, let's remember, includes PBC mortality but also mortality due to treatments and mortality due to other causes, smokers being exposed to other pathologies (emphysema, other cancers, cardiovascular diseases).
The Academy still says it does not want to return to the "irradiation controversy" the authors write: "... our report is factual on this point, and we encourage you to reread this paragraph. However, it is regrettable that in none of the trials was precise dosimetry performed."

The High Authority of Health, initially reluctant in 2016, completely changed its attitude and gave in 2022 its green light to an experiment on lung cancer screening, despite the ineffectiveness of this scannographic screening to reduce all-cause mortality.

"The HAS considers that the state of knowledge is still incomplete and insufficiently robust for implementing a systematic and organized screening of PBC (bronchopulmonary cancer) in France. However, the data shows a decrease in specific mortality and authorize the initiation of a pilot program to document: the modalities of screening, the performance/efficacy and efficiency, the organizational constraints, and the ethical and social dimensions by testing several possible scenarios and on several screening ranks.

Thus, the HAS recommends that experimentation be carried out in real life concerning the French healthcare system to answer the outstanding questions."

In its report on page 70, the HAS considers that "The meta-analyses do not show a significant reduction in all-cause mortality, whatever the procedures compared: this criterion of judgment is not very relevant because of the interference of age and chronic smoking on mortality, and the need for very long-term follow-up on a large cohort.

This means that the HAS does not recognize overall mortality as the primary efficacy criterion, puts specific lung cancer mortality ahead, ignoring other causes of smoking-related mortality and morbidity, and considers randomized studies with 10-year follow-up insufficient. This means that any unproven screening can be defended and maintained, as is the case with breast cancer screening, which is currently unable to prove its effectiveness.

A new study is published in 2022. This population-based ecological cohort study found that low-dose CT screening of low-risk, mostly nonsmoking Asian women was associated with significant overdiagnosis of lung cancer. Five-year survival is biased by the increased detection of indolent, early-stage lung cancers that would never have killed.
She concluded that unless randomized trials can show some value for low-risk groups, low-dose CT screening should remain targeted only at heavy smokers.

A HAS opinion on the relevance of screening

Dr. Catherine Rumeau-Pichon, Assistant to the Director of Medical, Economic and Public Health Evaluation, HAS, explained in this video from 5 years ago, that screening must meet the following six criteria:

1- A disease that can be detected early before the onset of symptoms

2- A reliable test

3- Effective treatments against the disease must exist

4- People at risk must be identifiable

5- Screening must be known to decrease cancer mortality.

6- The benefit/risk balance must favor a preponderant benefit over the risks.

Let's examine screening (breast, prostate) in the light of these criteria

1- Early detection of disease before symptoms.

For breast and prostate, not always...

Cancers with a long residence time in the breast, therefore not very progressive, are easily detected by screening before their symptoms because they are slowly progressive. They contribute to the overdiagnosis of many cancers.

On the other hand, cancers with a poor prognosis, with a high potential for progression and rapid growth, are 'missed' by screening because they are too fast to be 'caught' (these are the false negatives).

Their natural history is, therefore, not linear and predictable and is still not known at present. For prostate cancer, aggressive cancers often release their metastases from the start.

2- Reliability of the test

No

Mammography is a poor screening tool; it has good sensitivity for atypical lesions and in situ cancers, the least aggressive ones; it has poor sensitivity for high-stage cancers, triple negatives, and infiltrating forms.

The PSA level may be high in cases of simple benign prostate hypertrophy. A high level is not specific to cancer.

3-Effective treatments

Yes

For breast cancer, the effectiveness of treatments has improved significantly since the 1990s, and it is said that 9 out of 10 cancers are cured, even for those not detected.
For this reason, moreover, the usefulness of screening is diminishing.

Whether treated or not, prostate cancer rarely metastasizes (about 1 in 10 cases). When it does metastasize 90% of the time, it results in bone metastases.
While bone metastases usually have a poor prognosis for other cancers, this is not necessarily the case for prostate cancer. Whether it has metastasized or not, prostate cancer is often a slow-moving disease.
For this cancer, patient survival is improving year after year thanks to the appearance of new treatments and therapeutic combinations.

4-Identifiable persons at risk.

No

For breast cancer, risk factors predisposing to cancer can be identified, such as exposure to toxic substances, night work, and family history...
But not all women who smoke or work at night will automatically develop breast cancer, and there is no reliable link between a specific risk factor and breast cancer, not as clear-cut as smoking and developing bronchopulmonary cancer (and yet, here again, systematic screening of smokers is not recommended).

Only 5% of cancers are hereditary. This is too rare a phenomenon to impose screening on an entire healthy population with no family risk.

Women without risk, neither exposure nor intrinsic, can develop breast cancer without apparent 'reason.'

For prostate cancer, too, no risk factor has been identified and linked to this cancer.

5-Decrease in mortality

No

Impact studies have shown that mortality decline for several solid cancers has been effective since the 1990s and was not attributable to screening. This pattern of decline was also found for cancers not included in screening programs.

Breast: Norway study; impact study
Prostate: Ref: http://onlinelibrary.wiley.com/doi/10.1002/pros.20017/abstract; Labrie, Quebec, 2004

6-The benefit/risk balance in favor of the benefit

No

For the breast, this is no longer the case. Even in the most favorable hypotheses, such as the Marmot report, there is still more overdiagnosis than "lives saved."
M.G. Marmot, D. Altman, D. Cameron, J. Dewar, S. Thompson, M. WilcoxThe benefits and harms of breast cancer screening: an independent review Lancet, 380 (2012),. Marmot
Other independent reviews are even more severe; see our summary here: https://cancer-rose.fr/en/2020/12/15/the-over-diagnosis-in-a-graph-and-a-table/

When the three main disadvantages of systematic breast cancer screening are added: overdiagnosis, false alarms, radiation-induced cancers, and deaths attributable to overtreatment, the benefit/risk balance is always unfavorable.

For prostate cancer, really aggressive cancers release their metastases at the beginning of the disease. In this case, treatment will not protect against death. The treatments for this cancer have adverse effects that can be important (urinary incontinence, impotence). The patient's life will be altered more than "saved."
The elderly patient is more likely to die before from something other than his cancer.
Between 50 and 75, there is no proof that screening for this cancer would save people (HAS). The WHO does not recommend this screening either.

In the Canadian study, there is more mortality in the screened group because the risks of screening and the collateral effects of biopsies and treatments in screened men outweigh the benefit, which is minimal.

Overall all-cause mortality was almost the same in men who had surgery as in men who did not have surgery.

==> in total:

Of 6 requirements, breast and prostate cancer screening fail to meet 5 of them.

And nevertheless...

...the European Commission proposes at the end of 2022 an extension and/or a resumption of certain screenings and the 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.
In addition, lung and stomach cancer screening will be included, although no conclusive studies exist for the latter.

Many media have copiously relayed this information without any further critical analysis...

The European commissioner Mrs. Stella Kyriakides issued in September the following speech
"Today, we know that it is estimated that one in two EU citizens will develop cancer during their lifetime."

However, the European Commissioner fails to mention that life expectancy in Europe continues to increase.
This is pure fear-mongering, creating a feeling of urgency, threatening the population, and must be addressed with great diligence.
This is a well-known technique to push for a change to be immediate and experienced as necessary, as is advocated in the business world.

John P. Kotter, Professor at Harvard Business School, outlines the elements for management of change:
"To succeed in a project or a change, it is important to demonstrate the need for it. The most effective way is to trigger a need that your project will meet by creating a sense of emergency among all your employees. Expose the risks the company is taking by not changing the way it operates."

Conclusion

Cancer takes a particular place, unlike other pathologies, even the most serious or deadly. It has replaced the scourges of the Middle Ages, tuberculosis, and syphilis of our elders. It symbolizes insidious evil and is always associated with the silent killer.

Despite all the knowledge accumulated over the last decades on the flaws and failures of screening, the fear of cancer is so deeply rooted in us, perpetually conveyed by societal, medical, and media messages, that any call for caution about the myth of saving early detection is vain.

Advances have been made, thanks to the failure of screening, our knowledge has progressed on the mechanics of cancer evolution, and we have learned about the complexity of the natural history of the disease.

But often, during the media communication of the pink October campaigns, it is enough for one or several "cancer-survivor" stars, television hosts, or politicians to claim to have survived thanks to a "saving" screening, feeling missioned to carry his experience as exemplary and emblematic, presumptuously setting himself up as a spearhead of a "noble cause," for everything to be reconsidered.
Or a blind decision by the European Commission...

There is nothing more powerful than the infusion of terror to suppress all reasoned, prudent, and scientific argumentation and to sweep away all efforts of neutral and objective information of the population.

We have not learned from past medical errors, the history outlined at the beginning of this article shows to what extent decisions taken too hastily and prematurely in the implementation of screenings lead to health disasters, carefully concealed from the public to whom only "benefits" are dangled.
These disasters and endangerment of people continue, and the media only communicate very sparingly on this subject.
Many screenings, especially for breast cancer, should never have been done and have resulted in resounding fiascos (like thyroid, neuroblastoma in children, and melanoma).
The European Commission even plans to implement a stomach cancer screening for which there is NO scientific evaluation...

The future seems quite dark because, at this frantic pace of repeated screenings, the only healthy individuals will be the ones who escape these macabre rituals, renewed during their life like a morbid litany, and which will propel healthy people into diseases they should never have known.

Read also the last post of Luc Perino-(in French)

References


[1] Olsen, O., & Gøtzsche, P. C. Screening for breast cancer with mammography. The Cochrane Database of Systematic Reviews. 2001; (4): CD001877.

[2] Mammographies et dépistage des cancers du sein : Pour un choix éclairé des femmes désirant participer au dépistage. In : Prescrire. [En ligne : https://www.prescrire.org/aLaUne/ dossierKcSeinDepSyn.php]. Consulté le 12 mai 2021.

[3] Gøtzsche P. C., Nielsen M. Screening for breast cancer with mammography. The Cochrane Database of Systematic Reviews. 2009 Oct 7; (4): CD001877.

[4] Zahl PH., et al. WITHDRAWN: Results of the Two-County trial of mammography screening are not compatible with contemporaneous o icial Swedish breast cancer statistics. European Journal of Cancer. 2006 Mar 9.

[5] Zahl PH, et al. Results of the Two-County trial of mammography screening are not compatible with contemporaneous o icial Swedish breast cancer statistics. Danish Medical Bulletin. 2006 Nov; 53(4): 438-40.

[6] Gøtzsche P. C. What is publication? The Lancet. Nov 2006; 368(9550): 1854-56

[7] https://cancer-rose.fr/en/2021/01/01/critical-analysis-of-the-new-inca-information-booklet/

[8] https://cancer-rose.fr/2018/02/11/10552/

[9] https://cancer-rose.fr/en/2021/06/24/press-release-cancer-rose/

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

https://ec.europa.eu/commission/presscorner/detail/fr/QANDA_22_5584

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:
https://healthcare-quality.jrc.ec.europa.eu/european-breast-cancer-guidelines/screening-ages-and-frequencies/women-45-49#rec-question

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

Conclusion

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.

Screening for cancer: the Good, the Bad and the Ugly

‘On the Shoulders of Giants’ is a series of educational talks hosted by NCITA where experts bring their perspectives to encourage and challenge wider thinking within the cancer imaging research community.

Here a video-presentation by Michaël Baum, Professor Michael Baum is Emeritus Professor of Surgery and Visiting Professor of Humanities at University College London.

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

Preamble

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

Testimonials

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?

Références

[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.
https://pubmed.ncbi.nlm.nih.gov/35899737/
https://www.ntvg.nl/artikelen/kritische-blik-op-kankerscreening#popup-abstract-en

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

Abstract

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

Conclusion

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

References

1. Adami HO, Kalager M, Valdimarsdottir U, Bretthauer M, Ioannidis JPA. Time to abandon early detection cancer screening. Eur J ClinInvest. 2019;49:e13062. doi:10.1111/eci.13062. Medline

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

Abstract

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.

Conclusion

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

References

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.

Too much, too mild, too early: the excessive expansion of diagnoses

A summary of three articles

DOI https://doi.org/10.2147/IJGM.S368541

By Bjørn Hofmann 1, 2
1 Institute of Health Sciences, Norwegian University of Science and Technology, Gjøvik, Norway; 2 The Center of Medical Ethics, Faculty of Medicine, the University of Oslo, Oslo, Norway

Considerable scientific and technological progress has dramatically improved diagnosis. At the same time, false alarms, overdiagnosis, overmedicalization, and overdetection have emerged as corollaries compromising health care quality and sustainable clinical practice.

The article summarized here identifies three generic types of overdiagnosis: too much, too little, and too soon.

Due to significant scientific and technological advances, diagnoses have increased dramatically. More people are being diagnosed with more diseases than ever before, with an unwarranted expansion of diagnoses.

An increase in the number of diagnoses in the International Classification of Disease (ICD).

A-too many diagnoses:

This consists of labeling previously undiagnosed phenomena and including new phenomena in a pathology framework.
These may be a) ordinary life experiences, such as loneliness or grief, b) social phenomena, such as academic behavior in children (ADHD), or c) biomedical phenomena, such as high blood pressure, obesity, or risk factors that are measurable.
But this trend does not benefit individuals and can be harmful.

B-Diagnoses issued too lightly: setting thresholds too low and making it too easy to include in pathology

This is a lowering of the threshold for detection of pathology beyond what benefits the person, i.e., accepting threshold values that are too low.
By including less severe cases in the definition of disease or its diagnostic criteria, people may be diagnosed with diseases that may not bother them.
Examples include gestational diabetes and chronic kidney disease.

C- Diagnoses made too early:

Diagnosing conditions too early that will never impact individuals, detection of precursor or low-grade lesions, is consistent with overdiagnosis which leads to overtreatment.

Why is this harmful?

First, the author explains that our diagnostic capabilities far exceed our helping capabilities. Not only do we lack curative measures for all established diagnoses, but the many diagnostic technologies also come with errors, and we come to diagnose when it does not help people.
Although we can detect more phenomena than ever, we do not know if they are relevant in what they represent or predict.

A- over-diagnosing...

.... of biomedical phenomena when they are not experienced in pain, dysfunction or suffering leads to doing the wrong thing by applying inappropriate labels and treatments, diverting us from more effective measures and causing harm through treatment.
Mild hypertension or hyperglycemia, or various risk factors, such as obesity, are most often not experienced as painful or dysfunctional, but their treatment can introduce potential diagnostic and treatment-related harm.
For example, the increased use of statins inappropriately in people with no complaints leads to headaches, dizziness, constipation, diarrhea, muscle pain, fatigue, sleep problems, and decreased blood platelet counts. Here, getting an over-diagnosis can reduce the quality of life, cause anxiety and stigma.

B-In the case of a diagnosis made too lightly,

we inflate the diagnosis by including phenomena that are too mild to cause a symptom, pain, dysfunction, or suffering, and the treatment causes more harm than good.
In such cases, we provide unnecessary treatment and introduce potential harm through diagnosis and treatment.

C-Too early diagnosis,

(as in many screenings) leads to overdiagnosis and overtreatment and potential harm from both. The cases we detect and treat would never have caused the person problems if undiscovered.

Therefore, we violate the ethical principles of non-maleficence and beneficence.

In addition, we drain resources from health services (justice of care issue), and patients are unaware that they are overdiagnosed and overtreated (patient autonomy issue).

Other examples cited in the article:

Changing the definition of osteoporosis by modifying the T-score threshold that reflects bone density in the 2008 National Osteoporosis Foundation guideline increased the prevalence (present+new cases) from 21% to 72% in US women older than 65.
Changing the definition of prediabetes by fasting blood glucose in the 2010 American Diabetes Association criteria increased the prevalence from 26% to 50% in Chinese adults older than 18.

Conclusion

As a result, the author of the article suggests three ways to reduce excesses and advance higher-value care for the population: a)we must stop diagnosing new phenomena, b)we must stop diagnosing benign conditions, including lowering diagnostic thresholds, c) and we must stop looking for early signs and markers that do not cause pain, dysfunction, and suffering, and will not harm if undetected..

A more precise definition of overdiagnosis, the "too early" of the previous article

According to Jeffrey K Aronson, the concept of "Overdiagnosis" (the "too soon" of the previous article) includes 2 categories:
1° labeling people with a disease that, undiscovered, would not have harmed them ;
2° broadening the definition of a disorder to as many individuals as possible by changing the threshold of a diagnostic test (which is the same as "too light")

The author, a British clinical pharmacologist at the Centre for Evidence-Based Medicine (Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK), explains in his article published in the BMJ the genesis of this term, now included in the Mesh, (Medical Subject Headings) which is the reference thesaurus in the biomedical field.
Read here: https://www.bmj.com/content/375/bmj.n2854

In recent years says the author, "definitions (of overdiagnosis) that have been suggested include:
- "...people ...diagnosed with conditions that will never cause symptoms or death."
- "Diagnoses of a condition that, if not known, would not cause symptoms or harm to the patient in their lifetime."
- "(The act of) making people 'patients' unnecessarily, by identifying problems that would never have caused harm or medicalizing ordinary life experiences through expanded definitions of disease."

The last of these definitions include the two main factors that constitute overdiagnosis, although they are not synonymous with it: overdetection and over definition. "

The author further reminds us that overdiagnosis is not synonymous with a false alarm, although this confusion is often made. (Overdiagnosis: true lesion but whose discovery does not bring anything; false alarm: suspicion of cancer but which is not confirmed).

As a final thought, J. Aronson summarizes three different ways of turning people into "patients" or "sick":

1.         Labeling them with some condition that would not have harmed them if it had not been discovered; this is related to the heterogeneity of many conditions, resulting in a range of conditions within the category, not all of which require attention; this is called blurring within the disease category;
2.         Expanding the definition of a disorder to encompass more individuals; this has been attributed to what has been called the blurring of the outer boundary of a disease definition ;
3.         By labeling them with a category of illness that medicalizes ordinary experience, such as pregnancy, this phenomenon is known as "mongering."

A call from Canadian scientists

We conclude this article by quoting a call for action by Canadian scientists to improve health care education.

The authors write:
▸ Over the past decade, decisions about screening have become more complex owing to a better understanding of potential benefits and harms. Strongly held beliefs and screening advocacy from individuals and groups point to the need to understand and consider individual patient preferences and values in screening decisions.
▸ Many physicians, other health care providers, and learners find conflicting and misleading information on screening to be challenging.
▸ Most screening decisions include a trade-off between potential harms and benefits.
▸ Physicians should understand the evidence and communicate it using shared decision-making skills to arrive at an appropriate screening decision based on their patient's values and preferences.”

Many physicians, health professionals, and learners lack the necessary knowledge and skills related to screening challenges. Many lack critical thinking skills, statistical understanding, or communication skills.

The authors suggest a need to improve the training of physicians, health care professionals, and learners in screening, risk understanding, and risk communication.

Conclusion of the call:

There are two challenges:

The first challenge is the development of educational content related to key concepts related to screening.
The second challenge is the development of educational strategies to place the teaching and adoption of these concepts at the core of medical education among medical students, residents, and clinicians.

“Clinician teachers, learners, professional societies that develop guidelines, screening agencies, and academic institutions should reconsider the optimal approach to the uptake and implementation of guidelines. This change in focus should encompass the breadth of learners from undergraduate medicine to continuing professional development and the breadth of stakeholders from patients to agencies. Now is the time to swim against the tide and reconsider our approaches to teaching and communicating prevention and screening information, ensuring they encompass an understanding of complexity, core concepts, and best practices.”

References

  1. Hofmann B.
    Too Much, Too Mild, Too Early: Diagnosing the Excessive Expansion of Diagnoses. Int J Gen Med. 2022;15:6441-6450 https://doi.org/10.2147/IJGM.S368541

2. Viola Antao, Roland Grad, Guylène Thériault, James A. Dickinson, Olga Szafran, Harminder Singh, Raphael Rezkallah, Earle Waugh, Neil R. Bell 
À l’encontre du statu quo en matière de dépistage Canadian Family Physician May 2022, 68 (5) e140-e145; DOI: 10.46747/cfp.6805e140

3. Aronson J K. When I use a word . . . . Too much healthcare—overdiagnosis  BMJ  2022;  378 :o2062 doi:10.1136/BMJ.o2062

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 for older adults; a bad idea

Patient-Reported Factors Associated With Older Adults' Cancer Screening Decision-making: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/34748004/

Jenna Smith 1 2Rachael H Dodd 1 2Karen M Gainey 2Vasi Naganathan 3Erin Cvejic 2Jesse Jansen 1 2 4Kirsten J McCaffery 1 2

  • Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • 2Sydney Health Literacy Lab, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Objective of the study: 

To summarize the patient-reported factors associated with older adults' decisions regarding screening for breast, prostate, colorectal, and cervical cancer.

Method:

21 studies were included.

Factors associated with decision-making were synthesized into 5 categories: demographic, health and clinical, psychological, physician, and social system.

The most commonly identified factors included personal or family history of cancer, positive screening attitudes, routine or habit, gaining knowledge, friends, and a physician’s recommendation.

Results:

Although guidelines suggest incorporating life expectancy and health status to inform older adults’ cancer screening decisions, older adults’ ingrained beliefs about screening may run counter to these concepts.

Consequently, communication strategies are needed that support older adults to make informed cancer screening decisions by addressing underlying screening beliefs in context with their perceived and actual risk of developing cancer.

Cancer Rose commentary

We analyzed the CNGOF (CNGOF-French national college of obstetricians and gynecologists) campaign of 2019, a stunning "cry of alarm" for breast cancer screening in older women, with spectacular media coverage in a clear sky, while no country practicing screening recommends screening beyond the age of 74, nor even the WHO...

Why is this campaign, still relayed on this learned society's homepage, a danger to the elderly?

A study from the University of Leyden provides an answer.

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

Few trials have focused on screening women in old age. The study by researchers from the University of Leyden on data from the Netherlands, published in 2014 in the BMJ, makes up for this lack.

According to the authors, after the age of 70, organized breast cancer screening would be useless. Indeed, at this age, screening does not significantly improve the detection of advanced cancers but instead increases the number of overdiagnosis and, therefore, overtreatment.

In the Netherlands, breast cancer screening has been offered to women up to 75 since the late 1990s. "Yet there is no evidence that screening older women is effective," the study authors explain, citing that few trials have been conducted specifically on these age groups.

For the Dutch researchers, systematic screening after 70 years of age would mainly lead to the detection and treatment of lesions that would not have developed into disease during the life of the patients.

These unnecessary treatments have a considerable impact on health, and the co-morbidity of these older adults is too high, as they are less able to tolerate the side effects of treatments, such as surgery, radiotherapy, and chemotherapy.

For this reason, they recommend that generalized screening not be extended to those over 70 years of age and recommend an individualized decision based on life expectancy, breast cancer risk, general condition, and preference of the women concerned.

It should also be remembered that the immune system weakens with age. This means that we contract more cancers and infectious diseases.  All the organs become exhausted and function less well, and the healing and tissue regeneration faculties are lessened, all of which must be considered when administering heavy treatments.

Conclusion

A point of view published in the JAMA in 2019 raised the question of the relevance of screening for older adults. While all recommendations stop this screening at 74 years of age, it is unfortunately not uncommon to see people beyond that age being sent for screening and "check-ups."

The authors argue that the evidence of benefits for older adults is unclear, and the chance of harm becomes greater (e.g., overdiagnosis, burdens of additional testing, false-positive results, and psychological impacts).

Although aging-related concepts are challenging to communicate, older people must be counseled about the reduced benefit and increased chance of harm from screening associated with limited life expectancy and worsening health to make better quality screening decisions. Communication strategies are needed that support older adults in making informed cancer screening decisions.

The principle of non-maleficence implies not harming people, a principle that even a learned society like the CNGOF must adopt.

Glasgow-communication

The Australian author reported at this week's ICCH2022 INTERNATIONAL CONFERENCE ON

COMMUNICATION IN HEALTHCARE (September 5-9, 2022, Glasgow), the results of an interview-based study involving general practitioners regarding cancer screening in older adults.

General Practitioners' Approaches to Cancer Screening in Older People, A Qualitative Interview Study
https://each.international/eachevents/conferences/icch-2022/programme/

Session Description:

Background: Older adults continue to be screened for cancer with limited knowledge of the potential hams. In Australia, general practitioners (GPs) may play an important role in communication and decision-making around cancer screening for older people. This study aimed to investigate GP’s attitudes and behaviours regarding cancer screening (breast, cervical, prostate and bowel) in patients aged ≥70 years (as screening programs recently began targeting ages 70-74). Methods: Semi-structured interviews were conducted with GPs practising in Australia (n=28), recruited through multiple avenues to ensure diverse perspectives (e.g., practice-based research networks, primary health networks, social media, cold emailing). Transcribed audio-recordings were analysed thematically. Findings: Some GPs initiated screening discussions only with patients younger than the upper targeted age of screening programs (i.e., some thought 69 or 74 years). Others initiated discussions beyond recommended ages. When providing information, some GPs were uncomfortable discussing why screening reminders stop, some believed patients would need to pay to access breast screening, and detailed benefit and harms discussions were more likely for prostate screening. When navigating patient preferences, GPs described patients who were open to recommendation, insistent on continuing/stopping, or offended they were not invited anymore, and tailored their responses accordingly. Ultimately the patient had the final say. Finally, GPs considered the patient’s overall health/function, risk, and previous screening experience as factors in whether screening was worthwhile in older age. 

Discussion: There is no uniform approach to cancer screening communication and decision-making for older adults in general practice and limited understanding among both older people and GPs around why screening has an upper targeted age. Tools to support effective communication of the reduced benefit and increased chance of harm from cancer screening in older age are needed to support both older people and GPs to make more informed cancer screening choices.

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.

Overdiagnosis, the silent pandemic of the West?

May, 25th

http://www.publichealthtoxicology.com/Overdiagnosis-The-silent-pandemic-of-the-West-,145733,0,2.html

The use of so-called "preventive" medicine to maintain good health is an intense and widespread phenomenon in modern Western societies. Although this appears logical and may have a solid scientific basis because it reflects medical community recommendations, several questions that require further investigation arise.

The authors believe that the most serious issue with this behavior in relation to modern medicine is overdiagnosis.

"What is good health?" and "What is a medical problem?" "What exactly are we looking for in medical examinations?" and "What is the relationship between medicine, society, and its practices?"

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
https://www.phrp.com.au/wp-content/uploads/2022/04/PHRP32122208.pdf

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.

Why don’t we change our vocabulary?

May, 31th

https://philarchive.org/archive/LARCDS

This article argues that the phenomenon of overdiagnosis is linked to both our increasing knowledge of cancer and the fact that this new knowledge causes bias in cancer screening, but also to our approach to cancer and the associated medical vocabulary.

The authors selected two types of cancer as particularly exemplary: papillary thyroid cancer and carcinoma in situ of the breast.

The often militaristic semantics and abusive designations of "cancers" for lesions that are not life-threatening contribute to both an increase in societal anxiety and overdiagnosis, a real scourge of post-modern medicine.

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.