Category: News

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.

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.

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.

May 17, 2022

Article in Auntminnie

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

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

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

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

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

1° Cancer detection

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

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

2° Recall rates

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

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

What can we learn from this study?

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

3°How effective are synthetic mammography images?

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

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

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

4° Does tomosynthesis reduce mortality?

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

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

In conclusion

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

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

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

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

Commercial determinants of cancer control policy (Eurohealth)

https://eurohealthobservatory.who.int/publications/i/commercial-determinants-of-cancer-control-policy-(eurohealth)
European Observatory on Health Systems and Policies (downloadable)

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

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

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

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

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

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

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

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

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

Deceptive drifts

A-Innovation as a panacea

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

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

B- Screening

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

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

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

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

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

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

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

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

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

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

C-Hyper-technology

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

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

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

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

D-Lack of balanced media coverage

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

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

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

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

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

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

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

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

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

Range of ways in which private interests influence public health

1. Financial incentives affect all areas of health

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

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

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

2° Lobbying

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

3. Advertising

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

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

4° Economic factors

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

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

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

How can we do better?

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

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

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

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

JAMA Surg. Published online April 6, 2022. doi:10.1001/jamasurg.2022.0669
https://jamanetwork.com/journals/jamasurgery/article-abstract/2790973

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

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

Dr Crile’s recognition of the heterogeneity of cancer growth

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

Dr Criles uses an analogy of a barnyard pen :

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

Editor's note, another representation:

Limited (or Uncertain) Benefit

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

Poorly Recognized (or Hidden) Harms

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

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

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

Misleading Feedback, Financial Incentives, and Distraction

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

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

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

Pr Welsch's conclusion

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

References

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

2. Welch HG. Evidence on cancer screening efficacy in randomized trials & effectiveness in US practice. Accessed March 2, 2022.
https://csph.brighamandwomens.org/wp-content/uploads/2021/12/Evidence-on-Cancer-Screening-Efficacy-in-Randomized-Trials-Effectiveness-in-United-States-Practice.pdf

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

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

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

November 27, C.Bour MD

Angiomammography is a recent technology that is not useful for screening but in diagnosing lesions and for particular indications.

We're talking about it because it's a technique you've probably heard of, and the French Health Authority recently examined it.

What is angiomammography?

This procedure combines mammography with the injection of a contrast agent to analyze contrasting lesions. It is possible to differentiate benign from malignant tumors based on the tumor's vascular behavior, specifically the emergence and subsequent fading of the vascular enhancement.

Dual-energy approach

After injecting the contrast agent into the patient, mammography is conducted with two incidences (one frontal and one oblique per breast) in two acquisitions, one low and one high energy, as is usual.

The glandular tissue and fat can be separated by recombining the images produced with these two acquisitions, leaving just the contrast of the lesions of interest apparent on the recombined images.

The end result is a type of mapping that allows for visualizing highly vascularized lesions such as cancers.

However, the dose delivered to the gland is higher due to the repetition of the acquisitions, once at low and once at high energy. The additional irradiation is approximately 1.2 times the usual dose for each image.

Why no indication in screening for women at high risk of breast cancer?

This technology is more irradiating than conventional mammography; MRI appears to be more suited because we usually want to limit irradiation in this at-risk population, for whom ionizing radiation is a potential factor in cancer induction.

What is the advantage of this technique compared to MRI?

It is quick to perform. Because the same incidences are used, it is simple to analyze the images and compare them to earlier mammograms (faces, obliques).

It is, however, irradiating and is not recommended for women who are at high risk of cancer. There is always the potential of allergy to the injected contrast products, even if it is low.

HAS (French Health Authority) recommendations

Angiomammography could be used in the following situations:

• diagnostic impasses, to confirm the presence of a suspicious lesion or to rule out the presence of a lesion, although with necessary follow-up;
• when contrast imaging is required:
  - locoregional extension assessment (tumor size and search for additional lesions);
  - evaluation of response to neoadjuvant chemotherapy;
  - tumor evaluation before neoadjuvant chemotherapy, but experts noted that breast MRI is currently the reference examination in this indication.

Two situations to be considered:

Angiomammography is recommended in the following situations where MRI is contraindicated:

• diagnostic impasses;
• locoregional extension assessment of cancer;
• tumor evaluation before and after neoadjuvant chemotherapy.

In the absence of contraindications to MRI, angiomammography is recommended

• In assessing locoregional extension or before/after neoadjuvant chemotherapy, for evaluating the tumor size, particularly for its perfect correspondence with the mammography images.

According to HAS, a quality control policy should be implemented to ensure optimal doses are always used and that the facilities are monitored.
More robust performance studies and meta-analyses are needed to confirm the diagnostic efficacy of angiomammography.

The HAS recommends conducting clinical research studies to confirm diagnostic performance data, to demonstrate the clinical usefulness of angiomammography, define its role in the diagnostic strategy, and determine its impact on therapeutic management (number of biopsies, the relevance of the surgical decision, rate of reinterventions, etc.).

. 

References

https://www.edimark.fr/Front/frontpost/getfiles/24426.pdfhttps://www.has-sante.fr/jcms/p_3186760/fr/interet-de-l-angiomammographie-double-energie-dans-la-strategie-diagnostique-du-cancer-du-sein-rapport-d-evaluation

Summary Dr. Cécile Bour, November 15, 2021

About an article published on October 15 in The New York Times by Holly Burns, a San Francisco area writer who was diagnosed with breast cancer 4 years ago.

Holly Burns shares her experience, which is similar to that of other cancer "survivors," and which remains poorly expressed during the annual Pink October: "October is National Breast Cancer Awareness Month and I am a person who’s had breast cancer, which means for me October is basically 31 days of low-key PTSD.”

Pink October as a trigger for an "anniversary reaction"

Kathleen Ashton, a psychologist at the Cleveland Clinic Breast Center in Ohio, also testifies in the article, "Some do enjoy the opportunity to raise awareness, but the majority of my patients find the month distressing."

For some patients and former patients, the month of Pink October acts as a red flag that is waved and brings everything to the surface, with the procession of trauma that has often accompanied the patient's journey, from the announcement to the treatment.

Deborah Serani, a psychologist and professor at Adelphi University in New York, explains that anxiety at a particular time may be triggered because of a phenomenon known as the "anniversary effect" or "anniversary reaction," a unique set of thoughts or feelings that arise around the anniversary of a significantly traumatic experience.

Thus, explains the psychologist, anything that reminds us of the traumatic event experienced can provoke this "anniversary reaction".

A gap between marketing and real life

This month can be particularly difficult for those whose cancer is progressive and has progressed. "It can feel like only the happy stories are presented," testifies a 40-year-old woman, Emma Fisher, with stage 4 metastatic breast cancer.

"It's hard to see campaigns where "everyone is laughing and smiling and having bake sales and doing fun runs," she says. "It makes me feel invisible, it's almost like metastatic patients are this dirty little secret in the breast cancer world, because nobody wants to portray breast cancer as a killer."

In the book IM-PATIENTE, Maëlle, the young woman with advanced cancer who testifies, says something similar: "the hospital is decorated in pink for a month, all the nice grannies knit their little pink squares, and we make a pretty ribbon around the hospital, well, okay. Sure. But during Pink October, what stories are we talking about? We always tell the same stories. We talk about these warriors who started their enterprise while undergoing chemo and who have three children after their surgery.
It's always the same story. Have we ever heard during Pink October about women having metastatic cancer? I don't think so. Because it's not pretty, it's not glamorous, we don't talk about it. that's unacceptable." (June 2018)

Bri Majsiak, co-founder of a non-profit organization for people affected by breast and gynecological cancers, says, "Breast cancer lasts 365 days a year, not 31."

How do you get through the month of October with peace of mind?

Psychologist Dr. Ashton (Cleveland Clinic Breast Center in Ohio) advises women affected by breast cancer to limit exposure to things they might experience as upsetting, which can mean taking a break from social media, unsubscribing from as many marketing emails as you can, not being afraid to set boundaries with loved ones who don't understand why ex-patients and patients might find this month very painful to live with, or sharing with other women who may be feeling the same way.

While friends and family may assume this is a month of celebration for survivors, they "need to understand that a serious personal illness like breast cancer is a traumatic experience," Dr. Serani said.

A Charleston psychotherapist, Ms. Ilderton, also advises against making the survivor you know a 'case study,' she whose friend emailed a group using her as an example of why a mammogram was a must.

Bri Masiak advises that for those who wish to support Pink October, they should look carefully at where the proceeds go and consider whether it would be better to donate to a more focused local organization, or one that is helpful to women during their treatment, for example.

Indeed, the destiny of the funds collected is often very opaque, the marketing budget can represent an important part, and the part really devoted "to the cause" is not known by the donors. The stated purpose of the fundraising is often "research".

But....what research? Do we wonder which studies have really been financed, what are the results, what are the concrete advances for women while we have been running for decades and yet breast cancer still kills, and this since the 90s, 11,000 to 12,000 women/year? This leaves us wondering about the real impact of these costly campaigns.

Conclusion

During this great annual pink barnum, not very useful and in reality not very informative for women, we should at least be aware that it can be a vector of distress and painful memories for some of us.

We hope that future Octobers will be less pink, more discreet and less festive, more educational and more interactive with all women, the healthy ones, the survivors and the heavily affected ones, for a better information on breast cancer, in a neutral and objective way.

15th of October, 2021 

https://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publications/DEPLIANT-Depistage-des-cancers-du-sein.-Guide-pratique

In June 2021, the French National Cancer Institute (INCa) issued a new leaflet, in addition to the brochure published in 2017, sent to women one time for their first screening appointment at the age of 50. This new leaflet will be distributed to all women for the following appointments, beginning at the age of 52. 

here: PDF of the leaflet

 REMINDER: 

1) The 2015 citizen and scientific consultation [1] allowed for the expression of two scenarios: "Scenario 1: Termination of the organized screening program..."; "Scenario 2: Discontinuation of organized screening as it exists today [2],..." and the claim for women concerned by breast cancer screening to have "balanced and complete information." [3]

2) It took two years for the French National Cancer Institute to publish in 2017 a very insufficient brochure [4], barely mentioning the harms of screening (pain during the examination, overdiagnosis, etc.) but not detailing them, focusing mainly on the very meager benefits, which are advantageously put forward.

3) In an international study, INCa's lack of objective information and manipulative nature were questioned [5], as was already the case for the citizen and scientific consultation report.

Today, six years after the citizen consultation, INCa persists and signs.

The proof is this new leaflet, which will be included in future biennial invitations sent to women aged 52 and over.

Analysis

The poor informative content of this leaflet allows a rapid analysis: NONE of the adverse effects of screening are mentioned. 

Instead, it states:

"This early detection increases the chances of a cure: it allows 99 out of 100 women to be alive 5 years after diagnosis."

CAUTION: Being alive 5 years after a diagnosis does not imply that you have been "cured." 
What about this generously promoted survival? 
First and foremost, it would be more accurate to present the 5-year survival rates of 100 women who were screened and 100 who were not screened.

Here's an insightful article that explains what survival means and why it isn't a reliable indicator of screening effectiveness https://formindep.fr/cancer-des-chiffres-et-des-hommes/

This is what survival means:

 "Survival" measures the length of time the cancer is present or the length of time a patient lives with cancer, but it does not measure the longevity or life expectancy. 
Screening creates an optical illusion by anticipating the date of cancer onset by detecting it before any symptoms appear. While the result is the same, i.e., death regardless of the time of diagnosis, this creates the impression that the patient's life is being prolonged. In reality, screening does not affect t women's longevity; it simply shifts the "window of observation" in the disease's history.

A diagram from the WHO screening guide, page 47, illustrates this lead-time bias [6] :

Or in this diagram: [7]

"Lead-time bias occurs when screening finds cancer earlier than that cancer would have been diagnosed because of symptoms, but the earlier diagnosis does nothing to change the course of the disease" (National Institute of Cancer (NIH) USA).

To illustrate the situation differently, let's use an analogy: a train heading for Paris derails in Orleans at 3 p.m., causing the death of all passengers. If I boarded at Tours, I would have a survival of 30 minutes; if I boarded at Bordeaux, I would survive 2 hours. Artificially, we can say that people who boarded at Bordeaux have longer survival than those who boarded at Tours, even though they did the same thing: boarding the train at a given moment.

Thus, the extension of survival is the result of two phenomena: the efficacy of treatments that would extend the life of a cancer patient and the anticipation and detection of several lesions that would not have caused the death anyway. Nonetheless, not all over-diagnosed women die! As a result, there is an illusion of success in the case of breast cancer because we are diagnosing numerous lesions that would never have caused the death...

"Survival" is a poor indicator because it is used to describe something that it cannot: the effectiveness of screening.

The only indicators of the effectiveness of screening are the decrease in mortality and the reduction of advanced cancers. However, it is not enough to say: "THE EARLIER A BREAST CANCER IS SCREENED, THE GREATER THE CHANCES OF CURE," it is necessary to prove with data and the INCa, carefully omits this point in the leaflet...

Why is this leaflet outrageously dishonest and unethical?

1. Again, French women are not receiving the critical neutral information to which women in other countries are entitled. This is a serious breach of ethics.  Women citizens were indeed asking for easy-to-understand decision aids (pictograms). [8]

2. The information on the risks of screening is not directly available. The word "risk" is never even mentioned, which is a deceitful way to make this information as inaccessible as possible.

Indeed, we can read on one of the leaflet's pages, "To learn more, talk to your doctor or go to "cancersdusein.e-cancer.fr." 

If the woman invited to the screening wants to know the unfavorable effects, she must go to this website [9] and look for the section(s) dealing with these adverse effects herself. 

Overdiagnosis is never mentioned as a title on this website's home page; the risks of screening can be found by clicking on the inserts "the benefits and limits of screening" and "breast cancer screening, risk 0 or not?"

The word "limits" is misleading and not appropriate. In its French version of the guide, the WHO uses the term "effets nocifs" (in English: harms) of screening, which weighs against the benefits. [10]. 

For a woman to say that screening has limitations means that screening is not completely effective and that there are probably cancers that are missed. But this term does not imply that screening has risks.

3. Addressing citizens' requests does not mean that INCa can disseminate deliberately truncated, false, misleading, and incomplete information, embellishing the benefits and concealing the risks at the same time as the letter of invitation. This is yet another example of disregard for women who will never have access to the truthful information to which they are entitled.

4. This process, which is repeated every two years, is, of course, a strong incentive because of its repetition.

5. The initial brochure was incomplete and has not been modified since 2018 despite its shortcomings [4]. But at least it addressed the possibility of overdiagnosis. The 2017 brochure is aimed at women aged 50 who are invited to perform breast cancer screening for the first time. It is only sent for the first screening, so women who turned 50 before 2017, now aged 55 or older, have never received it and will have to rely on this misleading and incomplete leaflet issued in 2021.

6. This new leaflet is supposedly "based" on the 2017 brochure, misleading, as overdiagnosis is never mentioned.

7. The new leaflet says: "to know more, talk to your doctor or go to the website...". The general practitioner can certainly be contacted, but in reality, the woman makes an appointment directly with the radiology office, mainly because the information in the leaflet focuses all its communication on the benefits of screening, leaving the practitioner no opportunity to properly inform the patients before they go for mammography screening. In any case, what question would a woman ask her practitioner since the notion of "risk" does not appear anywhere in the brochure?

8. In the "key information" section, it is stated that mammography is "reliable." This information is again misleading since mammography exposes women to false positives (suspected cancers that are not confirmed) and false negatives (cancers that are hidden or develop between two mammograms and are, therefore, "missed" by screening).

Why is INCa so consistent in providing promotional information about mammography breast cancer screening? 

Why has INCa's biased promotional communication remained unchanged over the years? This is a question that everyone should ask.

Since the introduction of organized screening for breast cancer in 2004, scientific knowledge about mammography screening has advanced, but INCa's "communication" has not changed. INCa still presents screening as very beneficial to women, as it does in this leaflet, without mentioning what is debated in France and worldwide. The major benefit is still asserted even though it is increasingly being questioned.

Furthermore, many risks have been updated, but this brochure does not even use "risk," implying that they do not exist. The INCa replaces the term "risk" with "limit," which is never used in the scientific literature on the subject.

Why is this mode of communication being used? 

For all of its years, INCa has focused its communication on promoting breast cancer screening by mammography. This communication is very different from what is done in other countries. [8]

INCa's goal is not to correctly inform women about organized breast cancer screening by mammography but to intensify it to "win the European competition." And this is done blatantly, disregarding scientific knowledge on the subject. 

As proof: in its detailed report "Ten-year strategy 2021/2030 to fight cancer," we read INCa objectives on p20, "Achieve one million more screenings by 2025. It is up to us to exceed the coverage targets recommended at the European level in terms of screening and to join the leading group in terms of adherence (70% for the Organized Breast Cancer Screening ......., ". [11] 

The INCa appears to be only following orders from the authorities. On the other hand, citizens have the right to expect objective information from such a health authority rather than "propaganda." 

Why is it critical for citizens to have access to information that INCa does not provide?

INCa's role was defined at the time of its creation (article L1415-2 of the Public Health Code); it was given two contradictory missions: to inform (paragraph 3) and to promote screening (paragraph 6). 

"Informing" means providing unbiased information about the benefits and disadvantages of a public health system. "Promoting" means ensuring that the public is effectively influenced to adhere to it, which contradicts neutral information because it tends to conceal anything that dissuades people.

As a result, there is an irreconcilable incompatibility between these two missions, as well as a clear conflict of interest when, as with this unworthy leaflet, INCa can congratulate itself for responding to citizens' requests for information while ensuring that this information remains outrageously biased.

This is precisely what the INCa is doing with this brochure, which is akin to infantilizing women by maintaining them in ignorance, assuming their inability to make an independent choice.

According to a French publication, in order to increase screening participation, women who are called upon to undergo it should not be given information.[12]

Given this situation, doctors and patients will have to adapt and seek the information necessary for everyone to make informed decisions outside the communication of the French health authorities.

Example of a brochure

It is not surprising that this manipulative information comes from an institute that does not hesitate to label the scientific debate on screening as "Infox" or "Fake news." [13]

Our Cancer Rose collective began delivering more balanced information in a leaflet several years ago without any financial outlay. It is in A5 format, downloadable and foldable, and is intended for women and doctors to distribute to patients at the end of their consultation.

Our collective will make a point of informing the leaders of the INCa's International Scientific Council. We will notify international actors and groups fighting in many countries for women to be recognized as intelligent beings deserving of information to ensure their choices and autonomy in health matters within the framework of informed consent.

References

---

[1] https://cancer-rose.fr/en/2020/12/14/final-report-of-the-citizen-consultation-report-of-the-steering-committee/

[2] page 132-133 du rapport https://cancer-rose.fr/wp-content/uploads/2019/07/depistage-cancer-sein-rapport-concertation-sept-2016.pdf

Two scenarios proposed, both contain the words "stopping screening".

[3] page 128 du rapport https://cancer-rose.fr/wp-content/uploads/2019/07/depistage-cancer-sein-rapport-concertation-sept-2016.pdf

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

[5] https://cancer-rose.fr/en/2021/04/20/methods-of-influencing-the-public-to-attend-screenings/

[6] https://apps.who.int/iris/handle/10665/330852?locale-attribute=en&

[7] https://www.cancer.gov/about-cancer/screening/research/what-screening-statistics-mean 

[8] https://cancer-rose.fr/en/2021/06/28/other-information-tools/

[9] https://cancersdusein.e-cancer.fr/

[10] https://apps.who.int/iris/handle/10665/330852

[11] https://solidarites-sante.gouv.fr/IMG/pdf/feuille_de_route_-_strategie_decennale_de_lutte_contre_les_cancers.pdf

[12] https://cancer-rose.fr/en/2021/01/24/objective-information-and-less-acceptance-of-screening-by-women/

[13] https://cancer-rose.fr/en/2021/07/13/the-national-institute-of-cancer-in-france-inca-relegates-the-question-of-the-benefit-risk-of-organized-breast-cancer-screening-to-the-fake-news-rubric/