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/


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