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

A summary of three articles

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

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

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

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

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

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

A-too many diagnoses:

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

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

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

C- Diagnoses made too early:

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

Why is this harmful?

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

A- over-diagnosing...

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

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

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

C-Too early diagnosis,

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

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

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

Other examples cited in the article:

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

Conclusion

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

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

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

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

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

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

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

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

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

A call from Canadian scientists

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

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

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

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

Conclusion of the call:

There are two challenges:

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

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

References

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

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

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

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Overdiagnosis, the silent pandemic of the West?

May, 25th

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

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

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

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

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


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

Awareness of breast cancer overdiagnosis among women with breast cancer

June, 22

Effects of awareness of breast cancer overdiagnosis among women with screen-detected or incidentally found breast cancer: a qualitative interview study

This is a study conducted by an Australian team from the University of Sydney (Prof. Alexandra Barratt's team) that consists of qualitative research conducted through international interviews with women diagnosed with breast cancer who are aware of the concept of overdiagnosis.

The majority of the women who were followed became aware of overdiagnosis after their own diagnosis and felt impacted.

The discovery of overdiagnosis or overtreatment has had a negative psychosocial impact on the women's self-image and the quality of their interactions with health care professionals. For some, it has triggered deep remorse about their past decisions and actions.

The experiences of this small group of women provide unprecedented insight into the serious consequences of overdiagnosis after a breast cancer diagnosis.




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


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

Evaluation of information on screening, the situation in Italy, French parallel, and hope…

Synthesis Dr. C.Bour, May 11, 2022

https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-022-01718-w

According to the authors of this Italian study published in BioMed Central (BMC, a scientific journal) on April 22, 2022, information about overdiagnosis showed a notable increase in 2021 compared with 2014. However, the frequency of this information in the documents aimed at women was still low, probably because it is both the most recent and harmful risk for women. Therefore, not all health operators are aware of overdiagnosis. If they are aware of it, they might avoid reporting the information in public documents for fear of dissuading women from undergoing screening. Moreover, many reports of overdiagnosis are unclear.

It is difficult not to find a parallel with the situation regarding information in France.

This situation of insufficient information for women persists for many reasons.

One of the most frequently reported justifications is that providing information on potential harms could reduce adherence to screening.

Method and results

As information provided to women on the benefit-risk balance is still highly biased, F. Atténa (Department of Experimental Medicine, University of Campania "Luigi Vanvitelli") and her collaborators have decided to evaluate documents addressed to the general female public and published on the Internet by the Italian national and regional public health services.

Information on false positives and false negatives, biopsy-proven false positives, interval cancer, overdiagnosis, radiation exposure, and mortality risk reduction was analyzed. In addition, quantitative data were investigated.

The 2021 situation was compared with the 2014 situation.

Overdiagnosis and biopsy-proven false-positive results were the least reported risks of screening (20.1% and 10.4%).
Compared to the 2014 information, the 2021 information showed some improvements. The most marked improvements concern overdiagnosis. The declarations of this adverse effect increased from 8.0 to 20.1%.
Concerning the number of false positives proven by biopsy, there is also an increase in the information from 1.4 to 10.4%.
But quantitative data remained scarce in 2021.

The authors conclude with the evidence of moderate improvements in information observed from 2014 to 2021.

However, information about breast cancer screening in materials for women published on Italian websites remains too sparse.

A previous shocking Italian study from 2020

A study published in September 2020 by Italian authors moved us: this economic study explained how to effectively manipulate women to make them participate ever more in organized breast cancer screening by mammography. The authors then congratulated themselves with confusing cynicism on the effectiveness of manipulation techniques: by withholding information from women in the invitation letters, insisting on a negative effect and a potential danger of not participating in screening, by "limiting the cognitive overload of women" (sic), it would be possible to increase participation in screening significantly.

This kind of unethical study can explain, among other things, the persistence of misinformation of women and biases in the information, which are constantly renewed, as seen in this BMC study mentioned above.

A problem common to many countries, including France

Danish authors analyzed how health authorities can subtly influence citizens to participate in cancer screening programs: https://cancer-rose.fr/en/2021/04/20/methods-of-influencing-the-public-to-attend-screenings/

The researchers identified and analyzed several "categories of influence," i.e., several methods that can be used to push the public to undergo screening.

In a systematic table, we find that information bias is used in many countries, among which we find European countries like Italy, corroborating the finding of this BMC study, Spain, and also France, where biased information from the National Cancer Institute (INCa) is present in two of the systematic categories. See the table: https://cancer-rose.fr/wp-content/uploads/2021/04/Supplementary-Tables-Rahbak-et-al-210421.pdf

The INCa's disregard for information to women culminates with the qualification of the scientific controversy of screening as "fake news ." (Cf https://cancer-rose.fr/en/2021/06/24/press-release-cancer-rose/)

Hope for improvement and consideration of overdiagnosis

A position of French sociologists on the "health projects" of the next government can be read in the article "The main topics for the next Minister of Health" published in the media 20Minutes; they are alarmed by the overdiagnosis of organized screening (in the section "Prevention").

We can read:

 "We must be wary of organized screenings; it can generate overdiagnosis, criticizes Frédéric Pierru (doctor in political science, a sociologist at the CNRS, research fellow (CR-CNRS), works at the Center for Political and Social Administrative Studies and Research (CERAPS), attached to the University of Lille). This is an individualistic, medicalized, and poor vision of prevention". He believes that it would be more effective to put resources back into maternal and child protection centers (PMI), school medicine, occupational medicine...

"Effective prevention would mean addressing diet, stress, alcohol..." says Daniel Benamouzig (sociologist, Director of Research at the CNRS, holder of the Health Chair at Sciences Po, and researcher at the Centre Sociologie des Organisations (CNRS and Sciences Po)). We know that this President is not very inclined to oppose the alcohol or pesticide lobbies. Health, particularly public health and the ecological transition, is a long-term task. It is not easy to prove oneself in five years..."

Let's hope that these far-sighted scientists are heard...


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


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

A Modeling Study on Overdiagnosis

By the Cancer Rose Collective, March 12, 2022

https://www.acpjournals.org/doi/10.7326/M21-3577

According to a modeling study based on data from Breast Cancer Surveillance Consortium (BCSC), about one in six to seven screened breast cancer cases is overdiagnosed.

This study first highlights that overdiagnosis in breast cancer screening is real.

Results of study

An average of 15.4% (95% CI: 9.4%-26.5%) of screened cancer cases were estimated to be overdiagnosed, reports lead author Marc D. Ryser* of Duke University in Durham, North Carolina, and colleagues.

* Ryser: Marc Daniel Ryser, Assistant Professor of Population Health Sciences. Dr. Marc Ryser is an expert in mathematical and statistical modeling. His research uses biological, clinical, and population-level data to inform and guide the early detection and prevention of cancer.

Below are the results by age group and type of cancer detected (Figure 3 and Table 3).

Beyond the average values, we can observe (Fig 3) that for all age groups, the rate of overdiagnosis can reach maximum values higher than 20%, and according to Table 3, the rate of overdiagnosis at the first screening reaches a maximum value of 28%, at 58 years 21.1%, at 66 years 25.4% and at 74 years 31.9%

In this model study, an interesting finding is that the rate of overdiagnosis increased with age and almost doubled depending on the age range analyzed: 11.5% (95% CI, 3.8%-28.3%) at the first screening at age 50 to 23.6% (95% CI, 17.7%-31.9%) at the last test at age 74.

Comparison with previous data

The authors note, "comparison of our estimates against those from other studies is not straightforward because of differences in overdiagnosis definitions and screening practices."

They conclude that their results regarding overdiagnosis are both higher than previous modeling studies (ranging from 1% to 12%, depending on the studies cited in the article) because of differences in screening practices, diagnostic practices, and modeling assumptions, but lower than other studies that have shown rates much higher than the average in this study.
For example, the Canadian screening trial estimated an overdiagnosis rate of 30% (Baines CJ, To T, Miller AB. Revised estimates of overdiagnosis from the Canadian National Breast Screening Study. Prev Med. 2016;90:66-71. [PMID: 27374944] doi:10.1016/j.ypmed.2016.06.033 ) for cancers detected by screening.
In a population-based study, Bleyer and Welch (Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367:1998- 2005. [PMID: 23171096] doi:10.1056/NEJMoa1206809 ) estimated that 31% of all diagnosed breast cancer cases were overdiagnosed.

The authors conclude with the hope that their findings will join a consensus and facilitate decision-making regarding mammography screening.

Conclusions of the Editorial "Reducing the Burden of Overdiagnosis in Breast Cancer Screening and Beyond

The editorial published in conjunction with the study emphasizes the importance of informing women about what this overdiagnosis represents.
(Marcondes FO, Armstrong K. Reducing the Burden of Overdiagnosis in Breast Cancer Screening and Beyond. Ann Intern Med. 2022 March 1. doi: 10.7326/M22-0483. Epub ahead of print. PMID: 35226534.)

Authors underline: « Women who are considering having mammography screening should be counseled about the risk for unnecessary cancer treatment using this information."
Estimating that about 60% of the 280,000 cases of breast cancer diagnosed each year in the United States are discovered through mammography screening, eliminating overdiagnosis could save 25,000 women the cost and complications of unnecessary treatment.

"Substantial advances" in critical areas need to be made, according to the authors, including:
- Develop a better predictive capability to accurately identify tumors that will not progress
- Improve the accuracy of screening technologies to reduce the risk of overdiagnosis and improve the ability to detect breast cancer that has not been detected by mammography
-Implement prevention strategies to reduce the overall rate of breast cancer diagnosis, such as providing counseling on lifestyle changes and screening for genetic risk.

The authors of the editorial conclude: « Screening tests, whether for cancer or other conditions, can provide great benefit by detecting disease when it is more easily treatable. However, the risk of labeling millions of persons as having a disease without improving their outcomes is very real. For now, the key to navigating these tradeoffs remains open and effective physician–patient communication, rigorous evaluation of all proposed screening strategies, and continued investment in early detection research. We look forward to the day when making an early diagnosis always helps our patients achieve better outcomes. »

And the findings go beyond breast cancer screening.
"As screening and diagnostic testing continues to grow in clinical practice, the issue of overdiagnosis is being felt far beyond cancer screening. For some conditions, changing definitions have led patients to be labeled with a predisease state on the basis of a test result that was previously considered in the normal range. Although there are strong arguments in favor of early treatment to prevent long-term complications in many conditions, the reality is that, just as with cancer screening, there is little doubt that some patients diagnosed through a screening test would never have progressed and are likely to be receiving unnecessary treatment."

Comments and criticisms, opinion of Dr. V.Robert, statistician

1-A modeling study

The study remains a modeling study, which means that the results of a model depend on a chosen model and conditions of validity, at best unverifiable and at worst questionable. For example, the authors are obliged to consider that a breast cancer is either definitively non-evolving or inexorably evolving, with no possibility that the evolutionary status of cancer changes over time. It is not clear that things are that simple.

Another example is that the authors are obliged to build their model by considering that all progressive breast cancers evolve at the same rate and that this rate remains constant throughout the evolutionary period. In practice, there are most likely different distributions of progression rates for each type of breast cancer, and it is not clear that progression rates cannot vary over time.

2- The data on mortality from causes other than breast cancer used by the study do not seem well adapted.

On the one hand, after checking reference 25 of the study, which corresponds to the source of these data (Contribution of Breast Cancer to Overall Mortality for US Women): for a population of women aged 50 to 80 years, these data are not derived from direct measurements of mortality but from data estimated from projections (in other words, from models).

On the other hand, the data correspond to a cohort of women born in 1971. Since the median age of the women included in the study is 56 years, the cohort born in 1971 is adapted for the mortality of women included in 1971 + 56 = 2027. Or, if you prefer, the cohort adapted to have the mortality of women aged 56 in 2000-2018 should be born between 1944 and 1962. Whatever the reasoning, it is clear that the cohort considered to obtain the mortality data is too recent by at least a decade. This is not neutral since the tables in Reference 25 show a non-negligible decline in mortality over time.

3-The definition of screen-detected cancers is questionable.

Screen-detected cancers are considered to be those that meet the following two conditions: screening mammograms BI-RADS 3 to 5 + diagnosis of cancer within the next 12 months.
With criteria such as these, interval cancers are likely to be classified as screen-detected cancers (BI-RADS 3 + negative complementary examinations = screening showing no cancer; if a cancer occurs 11 months after the screening mammogram, it is an interval cancer, and yet it will be classified as a screened cancer). Even if these cases are not very frequent, they are part of the data used to adjust the parameters, and adjusting on "garbage in, garbage out" data can only give garbage results.

4- It is wrong to pretend that the study found that the overdiagnosis rate is 15%.

The reality is that the study shows that the overdiagnosis rate is somewhere between 9% and 27% (and any value within that range is possible, no more 15% than 9% or 27%).

Figure 3 from the study:

Depending on the age range, the percentage of overdiagnosis can vary up to 25% or even 32%.

Unfortunately, it is a very common mistake to take the result of a study (estimated rate from a sample) for the reality (real and unknown, rate in the population). And it is an even more common mistake to believe that the estimated rate is more likely to be close to the real rate than any other value in the confidence interval.

Conclusion

Based on such a study, we cannot arbitrarily consider that the debate on the frequency of overdiagnosis is closed, with a definitive frequency of 15%, as the study's authors would like.

On the other hand, the model may be interesting for answering questions about the evolution of the frequency of overdiagnosis as a function of the age of the women screened or about the evolution of the frequency of overdiagnosis as a function of the interval between two screening mammograms.    

Professor Alexandra Barrat of the University of Sydney, interviewed by Amanda Sheppeard, associate editor and reporter for Oncology Republic and The Medical Republic, said there are different methods for estimating the potential rate of overdiagnosis through breast cancer screening.
She said the study demonstrated the inevitability of overdiagnosis in screening for a number of cancers. "I think there is a need in the professional community for greater acceptance of what the evidence shows about breast cancer screening."
"We just need to recognize that this is inherent in a cancer screening program."

As a result, and beyond the evidence, according to A.Barrat, the study helped to underscore the importance of informed consent in breast cancer screening.

Conflicts of interests

Dr Ruth Etzioni - Individual investor and stock in Seno Medical  https://senomedical.com/clinical/product-applications

Seno’s first clinical product targets the diagnosis of breast cancer and will be used in addition to screening mammography, integrating opto-acoustics and ultrasound.

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


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

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

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

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

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

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

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

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

Prostate: beware of over-examination!

Philippe Nicot, University of Limoges

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

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

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

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

No established effect on mortality

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

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

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

Mass screening not recommended

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

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

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

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

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

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

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

A risk of impotence

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

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

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

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

What is the role of urologists?

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

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

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

No logo of the Urology Association

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

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

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

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

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

Philippe Nicot, teaching general practitioner, University of Limoges

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

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


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

Overdiagnosis of thyroid cancer, another woman’s concern

June 5, 2020

Summary, Cécile Bour, MD

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

IARC concerned about overdiagnosis of thyroid cancer

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

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

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

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

Overdiagnosis of cancers

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

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

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

Overdiagnosis of thyroid cancer

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

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

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

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

New IARC alert

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

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

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

In France

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

In all countries

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

The origin of the problem

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

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

 IARC Recommendation

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

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

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

Editor’s note

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

References

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

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

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

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


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

Carcinoma in situ, the problem of its overdiagnosis in screening mammography

Cécile Bour, MD

October 21, 2020

What is carcinoma in situ?

Carcinoma in situ (CIS) of the breast is defined by the proliferation of cancer cells within a milk duct without the cells spreading beyond the wall of the duct into the rest of the breast.

It is either strict ductal, developing in the milk excretory duct (ductal carcinoma in situ or DCIS), or in the lobule, the excretory unit around the duct (lobular carcinoma in situ or LCIS).

We have synthesized the main information in a summary for quick reading here: https://cancer-rose.fr/en/2020/11/30/what-is-a-ductal-carcinoma-in-situ-dcis/

In the media library you will also find some examples of images:

A very interesting blog by Donna Pinto is dedicated to DCIS with a lot of very practical and useful information: https://dcis411.com/

Ductal carcinoma in situ (DCIS) was rarely diagnosed before the introduction of breast screening, and now it accounts for 20-25% of all breast cancers, with this increase being directly correlated to over-detection by national routine breast cancer screening programs. 

Yet most DCIS lesions remain indolent. 

The problem

Despite being a pre-invasive or even non-invasive lesion, and although the natural evolution of this intra-ductal process is unknown, DCIS is still considered the early, non-obligatory form of (stage 0) breast cancer. The fear of not being able to distinguish between harmless lesions and potentially invasive forms, leads to over-treatment of this condition in many patients.

Therefore the classical patient management, and also in France, is to treat all DCIS lesions with a treatment that includes either mastectomy or breast conservative surgery supplemented by radiotherapy. 

The Marmot report in the United Kingdom (screening assessment report, 2012), recognized the burden of excessive treatment on women's well-being[1]. 

As a matter of fact, women with DCIS are labeled as "cancer patients", with concomitant anxiety despite the fact that most DCIS lesions are unlikely to ever progress to invasive breast cancer. ... The inflicted treatment (surgery followed or not by  radiotherapy) is therefore excessive for some, and very likely for many women, having a strong negative impact on their quality of life.

This particular form of cancer, that some call "pre-cancer" or " false cancer",  and some even consider as a non-cancer and only as a risk marker for breast cancer, greatly contributes to overdiagnosis, i.e. the discovery of abnormalities that, if they had remained unknown, would never have endangered the woman's life or health.

The problem with DCIS is that it is very easily revealed by mammography because of its association with calcifications, which are easily detected by mammography.

The data

The number of women diagnosed with DCIS in recent decades follows largely the introduction of  breast cancer mass screening, and is growing in parallel with the participation in screening[2] [3] [4] [5] [6].

The European standardised rate (i.e. the age-adjusted rate for the European population) of in situ lesions has quadrupled from 4.90 per 100,000 women in 1989 (representing 4.5% of all registered breast cancer diagnoses) to 20.68 per 100,000 women in 2011 (representing 12.8% of all registered breast cancer diagnoses[7] ). Of all reported in situ breast lesions, 80% are DCIS [8] [9].

Nevertheless, the incidence of breast cancer mortality has not decreased with the detection and treatment of DCIS, indicating that the management of DCIS does not reduce specific mortality from breast cancer.

A review of autopsies in women of all ages revealed a median prevalence (existing cases) of 8.9% (range 0-14.7%).  For women over 40 years of age, this prevalence was 7-39% [10], whereas breast cancer is diagnosed in only 1% of women in the same age group [11]. 

This means that these lesions are present more frequently than they are diagnosed in women in the living population, and that a large number of women carry undetected DCIS that would never become symptomatic, since more of them are found in women who have died from other causes than in the living population at the same time.

Classical lobular carcinoma in situ (LCIS), on the other hand, confers a risk of 1-2% per year of developing into invasive disease[12] [13].

What is also known, is that the stage of carcinoma in situ detected, is not a good and reliable indicator of the risk of progression of this lesion [14] [15].

In addition, patients diagnosed with DCIS have an excellent breast cancer specific survival rate, of approximately 98% after 10 years of follow-up [16] [17] [18] [19] and a normal life expectancy. If low-grade DCIS (considered a low-risk lesion) progresses to invasive breast cancer, it will often be a slow-growing, early-detectable, lower-stage invasive disease with an excellent prognosis.

However, despite this excellent prognosis and normal life expectancy, women diagnosed with DCIS suffer from stress and anxiety [20].  Studies report that most women with DCIS (and early breast cancer) have little knowledge about their condition and have misperceptions about the risk of disease progression, and this misperception is associated with significant psychological distress [21] [22] [23] [24] [25] [26].

In view of all these elements, it is considered that the current management of DCIS involves excessive treatment.

The problem of overtreatment

Currently, a conservative breast treatment for DCIS is frequently recommended. A mastectomy is advised if the DCIS is too large to allow breast conservation. Radiotherapy is often combined, which has been proven effective in reducing the risk of local recurrence.

However, it is also known that treating ductal carcinoma in situ does not reduce breast cancer mortality; also preventing recurrence by radiotherapy or mastectomy has also been shown not to reduce the risk of breast cancer mortality. Treatment would also not extend either breast cancer-specific survival or overall survival [27].

Due to the side effects of hormone therapy and ambiguous clinical trial results, postmenopausal women with DCIS are rarely treated with endocrine therapy in many countries. 

Some leads

Given the disappointing results of DCIS management in terms of reduction of invasive cancers, considering the absence of impact on survival, the implementation of treatments that were ultimately too severe for the results observed, and the major psychological impact, several countries have undertaken clinical trials aimed at testing a simple active surveillance, particularly for low grade CIS, rather than aggressive treatment.

Three clinical trials have randomized patients with low risk DCIS into two groups, one group under active surveillance versus one group receiving standard therapy. 

- COMET(US) [28] [29]
- LORIS(UK) [30]
- LORD(EU) [31]

A research program (PRECISION) has been initiated, encompassing these 3 international trials. https://www.dcisprecision.org/wp-content/uploads/2020/08/DCIS-Nieuwsbrief-Final_140820.pdf

CONCLUSION

There is an uncertainty regarding the manner in which DCIS develops, and there is a lack of global consensus on the best way to manage this lesion in an optimal manner. 

A better understanding of the biology of DCIS and the natural course of the disease is needed to help patients and health care professionals make more informed treatment decisions, to reduce the current over-treatment of DCIS that results in physical and emotional harm to patients and unnecessary costs to society. 

There is even an urgent need to reframe patients' perceptions of risk.

Initiatives and trials will hopefully contribute to better knowledge and informed decision-making between patients and clinicians.

Read also: https://www.nature.com/articles/s41416-019-0478-6

References

[1] Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet 380, P1778–P1786 (2012).

[2] Bleyer, A. & Welch, H. G. Effect of three decades of screening mammography on breast-cancer incidence. N. Engl. J. Med.367, 1998–2005 (2012).

[3] Bluekens, A. M., Holland, R., Karssemeijer, N., Broeders, M. J. & den Heeten, G. J. Comparison of digital screening mammography and screen-film mammography in the early detection of clinically relevant cancers: a multicenter study.Radiology 265, 707–714 (2012).

[4] Ernster, V. L., Ballard-Barbash, R., Barlow, W. E., Zheng, Y., Weaver, D. L., Cutter, G. et al. Detection of ductal carcinoma in situ in women undergoing screening mammography. J. Natl. Cancer Inst. 94, 1546–1554 (2002).

[5] Esserman, L. J., Thompson, I. M. Jr. & Reid, B. Overdiagnosis and overtreatment in cancer: an opportunity for improvement.JAMA 310, 797–798 (2013).

[6] Kuerer, H. M., Albarracin, C. T., Yang, W. T., Cardiff, R. D., Brewster, A. M., Symmans, W. F. et al. Ductal carcinoma in situ: state of the science and roadmap to advance the field. J. Clin. Oncol. 27, 279–288 (2009).

[7] https://www.nature.com/articles/s41416-019-0478-6

[8] Kuerer, H. M., Albarracin, C. T., Yang, W. T., Cardiff, R. D., Brewster, A. M., Symmans, W. F. et al. Ductal carcinoma in situ: state of the science and roadmap to advance the field. J. Clin. Oncol. 27, 279–288 (2009).

[9] Siziopikou, K. P. Ductal carcinoma in situ of the breast: current concepts and future directions. Arch. Pathol. Lab. Med.137, 462–466 (2013).

[10] Welch, H. G. & Black, W. C. Using autopsy series to estimate the disease ‘reservoir’ for ductal carcinoma in situ of the breast: https://www.acpjournals.org/doi/10.7326/0003-4819-127-11-199712010-00014

[11] Siziopikou, K. P. Ductal carcinoma in situ of the breast: current concepts and future directions. Arch. Pathol. Lab. Med. 137, 462–466 (2013).

[12] Lakhani, S. R., Audretsch, W., Cleton-Jensen, A. M., Cutuli, B., Ellis, I., Eusebi, V. et al. The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)? Eur. J. Cancer 42, 2205–2211 (2006).

[13] Ottesen, G. L., Graversen, H. P., Blichert-Toft, M., Christensen, I. J. & Andersen, J. A. Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study. Breast Cancer Res. Treat. 62, 197–210 (2000).

[14] Elshof, L. E., Schaapveld, M., Schmidt, M. K., Rutgers, E. J., van Leeuwen, F. E. & Wesseling, J. Subsequent risk of ipsilateral and contralateral invasive breast cancer after treatment for ductal carcinoma in situ: incidence and the effect of radiotherapy in a population-based cohort of 10,090 women.Breast Cancer Res. Treat. 159, 553–563 (2016).

[15] Bijker, N., Peterse, J. L., Duchateau, L., Julien, J. P., Fentiman, I. S., Duval, C. et al. Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853. J. Clin. Oncol.19, 2263–2271 (2001).

[16] Worni, M., Akushevich, I., Greenup, R., Sarma, D., Ryser, M. D., Myers, E. R. et al. Trends in treatment patterns and outcomes for ductal carcinoma in situ. J. Natl. Cancer Inst.107, djv263 (2015).

[17] Morrow, M. & Katz, S. J. Addressing overtreatment in DCIS: what should physicians do now? J. Natl. Cancer Inst. 107, djv290 (2015).

[18] Fisher, E. R., Dignam, J., Tan-Chiu, E., Costantino, J., Fisher, B., Paik, S. et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer 86, 429–438 (1999).

[19] Elshof, L. E., Schmidt, M. K., Rutgers, E. J. T., van Leeuwen, F. E., Wesseling, J. & Schaapveld, M. Cause-specific mortality in a population-based cohort of 9799 women treated for ductal carcinoma in situ. Ann. Surg. 267, 952–958 (2017).

[20] Ganz, P. A. Quality-of-life issues in patients with ductal carcinoma in situ. J. Natl. Cancer Inst. Monogr. 2010, 218–222 (2010).[21] Hawley, S. T., Janz, N. K., Griffith, K. A., Jagsi, R., Friese, C. R., Kurian, A. W. et al. Recurrence risk perception and quality of life following treatment of breast cancer. Breast Cancer Res. Treat. 161, 557–565 (2017).

[22] Ruddy, K. J., Meyer, M. E., Giobbie-Hurder, A., Emmons, K. M., Weeks, J. C., Winer, E. P. et al. Long-term risk perceptions of women with ductal carcinoma in situ. Oncologist18, 362–368 (2013).

[23] Liu, Y., Pérez, M., Schootman, M., Aft, R. L., Gillanders, W. E., Ellis, M. J. et al. A longitudinal study of factors associated with perceived risk of recurrence in women with ductal carcinoma in situ and early-stage invasive breast cancer. Breast Cancer Res. Treat. 124, 835–844 (2010).

[24] van Gestel, Y. R. B. M., Voogd, A. C., Vingerhoets, A. J. J. M., Mols, F., Nieuwenhuijzen, G. A. P., van Driel, O. J. R. et al. A comparison of quality of life, disease impact and risk perception in women with invasive breast cancer and ductal carcinoma in situ. Eur. J. Cancer 43, 549–556 (2007).

[25] Partridge, A., Adloff, K., Blood, E., Dees, E. C., Kaelin, C., Golshan, M. et al. Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: longitudinal results from a cohort study. J. Natl. Cancer Inst. 100, 243–251 (2008).

[26] Davey, C., White, V., Warne, C., Kitchen, P., Villanueva, E. & Erbas, B. Understanding a ductal carcinoma in situ diagnosis: patient views and surgeon descriptions. Eur. J. Cancer Care 20, 776–784 (2011).

[27] https://jamanetwork.com/journals/jamaoncology/fullarticle/2427491

[28] Comparison of operative versus medical endocrine therapy for low risk DCIS: the COMET Trial. http://www.pcori.org/research-results/2016/comparison-operative-versus-medical-endocrine-therapy-low-risk-dcis-comet.

[29] Hwang, E. S., Hyslop, T., Lynch, T., Frank, E., Pinto, D., Basila, D. et al. The COMET (Comparison of Operative to Monitoring and Endocrine Therapy) Trial: a phase III randomized trial for low-risk ductal carcinoma in situ (DCIS). BMJ Open 9, e026797 (2019).

[30] Francis, A., Thomas, J., Fallowfield, L., Wallis, M., Bartlett, J. M., Brookes, C. et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur. J. Cancer 51, 2296–2303 (2015).

[31] Elshof, L. E., Tryfonidis, K., Slaets, L., van Leeuwen-Stok, A. E., Skinner, V. P., Dif, N. et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study. Eur. J. Cancer 51, 1497–1510 (2015).

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


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

Breast Cancer Screening, a good intention, a bad theory, an aberrant result

Une bonne intention, une mauvaise théorie, un résultat aberrant Volume 2, issue 8, Octobre 2006, DOI: 10.1684/med.2006.0009  

Concepts

With 11,172 deaths in metropolitan France in 2002, breast cancer is a major public health problem. It is responsible for 19% of women deaths from cancer and 31% of malignant tumor deaths before the age of 65. Mass screening has intensified in France over the past several decades. The size of the tumor has never ceased to decrease at the time of diagnosis, but the mortality rate has remained desperately stable from 1980 to 2000. Over the same period, the annual number of diagnosed breast cancer cases doubled. These findings bring into question the soundness of screening and the necessity to quantify overdiagnosis.

Bernard Duperray St Antoine Hospital, Radiology Department, Paris
Bernard Junod National School of Public Health, Assessment of risks related to the environment and the health care system Rennes
Keywords : benefit/risk, breast cancer, screening DOI: 10.1684/med.2006.0009

It is claimed that after an initial preclinical phase of several years, the threshold for clinical detection is reached when the tumor measures approximately 1 cm. Thanks to mammography, screening would take place 1 to 3 years earlier, thus limiting the possibility of developing metastases that would only occur at a given tumor size.

These phases are assumed to mechanically follow one another[1]. A small volume lesion would mean an early diagnosed lesion. "Small" and therefore "early" would be synonymous with curable. The classic pattern (Figure 1), where atypical epithelial hyperplasia develops into cancer in situ and then into invasive cancer which gradually increases to a critical size, suggests that the use of screening could be sufficient in breaking this sequence before invasive cancer develops.

Yet, clinical findings in daily practice show that the progression of the disease is neither linear nor obligatory over time. Sudden changes, static situations and even regressions are observed."Small" does not mean "early". A tumor can develop clinically in a few weeks or even days. A millimetre-sized lesion can be associated to metastases, just as a small tumor which can remain small for many years without becoming a deadly cancer. On the other hand, large, widespread tumors may have no radiological translation.

Although the size of the tumor is apparently associated with the prognosis, it is not with time. In his reference book on breast diseases[2], Professor Charles Gros noted as early as 1963: "The chances of survival with our locoregional therapeutics are linked to the small size of the intramammary lesions. But the smallness of intramammary lesions is only very partially related to time. There is no rigorous parallelism between early diagnosis in time and in space". In most cases, ductal cancer in situ does not evolve into an invasive lesion .

A revision of more than 10,000 breast biopsies completed in Nashville, Tennessee, between 1952 and 1962, revealed cancers in situ in women who were considered not affected by cancer and therefore untreated. After 10 years, 75% of these women did not develop invasive cancer [3]. A wide range of potential clinical evolutions are observed for the same histological abnormality that defines breast cancer : some cancers develop and kill no matter what is done, others seem to respond to treatment, some remain silent, some regress or even disappear spontaneously. The alternative model diagram ( figure 1) takes into consideration these observations.

The question is to know whether these two types of cancer that can not be histologically distinguished are the same disease with varying evolutions, or whether they are entirely different entities with the same breast  stigma.

At present, breast cancer in all its histological forms is a disease whose natural history is not well known and whose strictly histological definition is reductive at a given time, once associated with a linear evolutionary model.

The drop in mortality is not there in spite of screening

The only argument for continuing screening despite scientific evidence was the result of some randomized studies, such as the so-called "two Swedish counties" study published in 1985. It promised women who would be screened a 25-30 % reduction in breast cancer mortality.

Examination of all the results of the seven controlled trials, including a mammography screening, shows the level of knowledge available on its effectiveness. Figure 2 illustrates, first of all, that the importance of mortality value varies between studies. This is mainly due to variations in the age structure of the cohorts of women studied.  The greatest difference in mortality between the screened and the control group is noted in the Edinburgh and Guildford study. It is now acknowledged that this difference is the result of a flaw in the so-called random allocation of women to each group.

Thus, this study does not allow to argument for or against the screening.The second largest difference observed is headed in opposite direction in a Canadian study. This result also prompted to an expertise on the quality of random allocation.

However, after this expertise, the procedures used and the results obtained were considered as valid. Overall, the differences in mortality between studies are not coherent, both in terms of their meaning and their importance [6, 7]. This finding is consistent with the Cochrane review published in 2001 [8]. In particular, it highlighted the precarious nature of the study of the two Swedish counties and of the Health Insurance Plan in New York, once we take into account the method of drawing the samples, the comparability of the groups, the exclusions during the study after randomization and the way in which death was attributed to breast cancer. This may explain why in Sweden, where screening has the longest tradition, the gain in mortality noted in practice is insignificant: 0.8% for 11% expected.

Although the reduction in mortality is not met, the perverse effects are present

The title of the lecture presented  in the summer of 1994 already by Dr. Marie-Hélène Dilhuydy asked the following question about screening : “A generous and life-saving purpose or a sanitary ideology with a perverse ethic, is the breast cancer screening useful for women ?” She clarified that mass screening probably reduces breast cancer mortality, but that the benefit is very limited and very difficult to demonstrate before alerting about the perverse effects that have already been observed. Since then, the extent of these effects has led to a continuous reconsideration of the practical modalities of screening.

False-positives

This refers to women who test positive even though they are not affected by cancer. The rate of false-positive mammograms has been particularly studied in Great Britain. Cumulative risk of false-positives after 10 mammography tests is 49.1%.

The positive predictive value (PPV) represents the probability that a woman with a positive test is affected by the disease. In France, the PPV for mammography testing using a single image per breast has never exceeded 9% at best, whereas a test judged as good should reach at least 30% or more [9]. Thus, 91% of women with a positive test were alarmed and had to undergo unnecessary diagnostic tests. The consequences are more and more aggressive complementary tests, including even biopsy, since it is becoming more and more difficult to reassure without histological evidence.

The evolution of the classification of radiological images according to the Breast Imaging Reporting and Data System (BIRADS) of the American College of Radiology (ACR) illustrates the difficulty of trying to make a practical attitude dependent on an imagery which is not very sensitive and not very specific.

The classification of microcalcifications in ACR 3, which should lead to easy monitoring, has been progressively diminished in favor of ACR 4, where histological verification is recommended. These tests are all the more inevitable as patients are firmly convinced that the smallest delay in diagnosis leads to a loss of chance and considerable prejudice [10].

Overdiagnosis and overtreatment

This is definitely a major deleterious effect of screening. It corresponds to diagnosis by excess. Overdiagnosis does not only concern cancers in situ but also invasive cancers that are slowly evolving or regressing spontaneously. It corresponds to the detection of cancer cells that would never have evolved.

As shown in figure 3,  there has been an "epidemic" increase in breast cancer diagnosis in France since 1980 [11]. How can that be explained?

An advance in diagnosis reaching an average of 12 months would only lead to 10% of the rise observed between 1980 and 2000. If this "epidemic" of diagnoses reflected a real increase in the incidence of progressive cancers, therapeutic effectiveness would have to be significantly improved. Indeed, we had only one cancer cured for a lethal cancer in 1980, while we have three cancers cured for a lethal cancer in 2000. In view of the results of controlled trials and the relative stability of treatment methods, such progress is implausible.

Another way to address the issue of over-diagnosis is to evaluate the reservoir of asymptomatic breast cancers present in the population of women. What is clinically observed is only the tip of the iceberg. Similarly to prostate cancer, there are occult breast cancers that will not reveal themselves during the patient's lifetime. Evidence of this is illustrated by a series of autopsies performed on women who did not know they had breast cancer during their lifetime. Studies published between 1984 and 1988 provide the results of a systematic search for breast cancer in a series of autopsies that were not selected on the basis of breast pathology. They concern, for example, women who died of a violent death and were examined in a forensic medical institute.

The difference between the number of invasive cancers diagnosed at autopsy and the expected number estimated from the incidence data for the time is considerable: there are more invasive cancers and, above all, far more in situ cancers at autopsy. The discovery of these cancers was all the more frequent as the number of cuts made by anatomopathologists increased. Thus, the more we search, the more we find [12].

More recently, longitudinal observations have documented the existence of overdiagnosis. Since mammography screening has existed for several decades, there are now sufficient retrospective data to show that cohorts of women with multiple screening examinations in succession had significantly more diagnoses than those screened only at the end of an equivalent observation period [5, 13].

Overtreatment is a consequence of overdiagnosis, whose it enhances its deleterious effects. Paradoxically, the results of the treatment of quiescent or pseudo-cancers are always considered to be satisfactory since they do not threaten the woman's life.

Importunate treatment

Several publications report the acceleration of metastases in vital organs following diagnostic and/or therapeutic interventions in breast cancer [4, 14]. Among the mentioned mechanisms, these authors suggest, for example, that a blunt diagnostic or therapeutic procedure releases circulating products responsible for stimulating metastases or that the excision of the primary tumor removes an inhibition of their growth.

Irradiations

Even if irradiation can be controlled and assessed by a quality procedure, its repetition in increasingly short periods of time represents an accumulation of small doses that increase the risk of cancer. According to estimates by the National Cancer Institute in the United States, an accumulated individual dose of 10 mSv would lead to between 9.9 and 32 cancers per million women. Patients carrying the BRCA genes show an increased radiation risk in vitro, yet they are proposed annual check-ups starting already at 30 years of age.

Perspectives of salutary advances?

Following the logic of a theoretical model based on the linear evolution of cancer, industrialized countries have engaged in screening programs to solve the problem of breast cancer mortality. The major concerns of French screening are currently of two kinds: its accessibility for all women and the improvement of senology practices. Thus, the National Cancer Institute is seeking to establish a culture of screening and to strengthen quality control, both in terms of the training of the practitioners involved and of the equipment they use. The interest in cancer screening has revealed its ineffectiveness. The indicators chosen to observe the disease do not allow progress to be made in understanding it. They create perceptions that contradict reality.

The mortality rate remains desperately stable in France, even though all the indicators used are reassuring: reduction in tumor size, reduction in the number of lymph node invasions and detectable metastases upon discovery of the disease, apparent improvement in survival at 5 or 10 years.

In most industrialized countries, two observed contradictory trends need to be clarified and quantified : on the one hand, iatrogenic effects due to inadequate therapies, considering the diversity of the evolution of the disease, of which the natural history is not well known, that contributes to deterioration of the prognosis, and on the other hand, therapeutic advancement in relation to better targeted treatments that improve survival.

In the current context, overdiagnosis inevitably leads to unnecessary and dangerous overtreatment, since lesions unjustifiably diagnosed as cancerous "diseases" would never have manifested themselves. Such "successes" are used to justify the continuation of the screening. They reassure practitioners that their activity is well-founded, while they only mask the ineffectiveness of the followed directions.

Potential improvements as a result of awareness-raising of the extent of the observed facts are considerable.

Conclusion

The willingness to act through systematic screening for a disease whose causes and natural history are not well known implies major disadvantages, in particular :

- unnecessary diagnostic tests;

- harmful treatment of tumors that would have had no consequences if they had not been diagnosed;

- possible acceleration of the manifestation of metastases;

- the induction of cancers by ionizing radiation in a healthy population.

A reorientation of research and health care is necessary to improve the specificity of the definition of cancer and limit the downside of a generalized systematic screening.

Conflicts of Interest: The authors declare that they have no conflict of interest in the subject covered by this article.

Summary: Breast Cancer Screening

Insufficiencies in the definition of breast cancer based on the results of punctual examinations and a linear theoretical model of the history of the disease bring into question the validity of its systematic screening.

Overdiagnosis and overtreatment are the major risks to avoid.

Click on images to enlarge

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L’attribut alt de cette image est vide, son nom de fichier est Diapositive1-3.jpeg.

Références :

1. Ménégoz F, Chérié-Challine L, et al. Le cancer en France : Incidence et mortalité, situation en 1995 et évolution entre 1975 et 1995. Ministère de l’emploi et de la solidarité et réseau Francim eds. Paris : La Documentation française ; 1998.

2. Gros C. Les maladies du sein. Paris : Masson, 1963, 573 pp.

3. Page DL, Dupont WD, Rogers LW, et al. Continued local recurrence of carcinoma in situ 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995;76:1197-200.

4. Baum M, Demicheli R, et al. Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases? Eur J Cancer. 2005;41:508-15.

5. Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ. 2004;328:921-4.

6. Black CB, Haggstrom DA, Welch HG. All-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst. 2002;94:167-73.

7. Mammographies et dépistage des cancers du sein. La revue Prescrire. 2006;272:348-71.

8. Olsen O, Gotzsche PC. Cochrane review on screening for breast cancer with mammo-graphy. Lancet. 2001;358:1340-2.

9. Renaud R, Gairard B, Schaffer P, Haehnel, Dale G. Définition et principes du dépistage du cancer du sein. 11 Journées de la Société Française de Sénologie et de Pathologie Mammaire, Tours, septembre 1989.

10. Berlin L. Malpractice issues in radiology. The missed breast cancer : perceptions and realities. AJR. 1999;173:1161-7.

11. Remontet L, Estève J, Bouvier et al. Cancer incidence and mortality in France over the period 1978-2000. Rev Epidemiol Santé Publique. 2003;51:3-30.

12. Welch HG. Dois-je me faire tester pour le cancer ? Peut-être pas et voici pourquoi. Laval ; Presses de l’université : 2005, 263 pp.

13. Zackrisson S, Andersson I, Janzon L et al. Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study. BMJ. 2006;332:689-92.

14. Cox B. Variation in the effectiveness of breast screening by year of follow-up. J natl Cancer inst. Monogr 1997;22:69-72.

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Cancer regression

June 25, 2020, summary by Cécile Bour, MD

G. Welsch, professor at the Center for Surgery and Public Health Brigham and Women's Hospital proposes an analysis of breast cancer screening by MRI in an educational video, using data from the "DENSE" trial (results published in 2019), with the reservations (see comment at the end of the article) that were expressed after the publication of the results in the NEJM.

What is this trial?

This is a randomized trial, of good quality.

Explanation of the method on the video at 1:12 video.

The researchers divide 40,373 women aged between 50 and 75 years of age, with extremely dense breast tissue and negative results on the initial screening mammogram, into two groups: in the " supplementary MRI" group or in the "screening mammogram only" group; more precisely 8,061 women in the "MRI invitation" group and 32,312 women in the "mammogram only" group.

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

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

Additional MRI screening appears to be associated with fewer interval cancers compared to mammography alone in women with extremely dense breast tissue.

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

However, in the analysis of these results, one important element is missing, according to G.Welsch: the exhaustive counting of all cancers in both groups.

The fact that there are more cancers in the screening-MRI group compared to the non-MRI group suggests that there are more detections with MRI. But this finding may also suggest something else, supporting the theory of variable kinetics of breast cancers: all cancers do not have same expression pattern, some of them possibly regress.

Regression of cancers?

We remind that this is a randomized trial. Since women are randomly assigned to one or the other group, it is expected that after two years we should have the same overall cancer rate in both groups.Video at 2:03

Cancers not anticipated by screening in women from the group without MRI would be necessarily expected to express themselves at the end of two years on the mammogram performed for both groups at the end of the study.

What is actually observed?

 - No cancer found at the initial mammogram in either group.

 - Globally more cancers found in the MRI group

- Fewer interval cancers in the MRI group

- At the end of the two-year control mammogram for end of the study, more interval cancers in the non-MRI group, as they were not anticipated by MRI.

 - Fewer mammographic cancers at the end of two years for the MRI group since a fraction is anticipated on MRI.

===> In total, we get an excess of 5.4 cancers found in the MRI group (Video 3:34)

G.Welsch explains: in a randomized trial with two random distribution groups, what is expected is that at the end of the study we will have a similar 'total cancer' rate, since cancers not anticipated by MRI in the non-MRI group are logically detected later on the control mammogram done at the end of two years.

The picture illustrates the group of women screened with additional MRI on the left and the control group without MRI on the right. We see in the red column all the cancers detected by MRI resulting in an excess of detection; the green squares indicate the interval cancers which are more present in the group without MRI as they were not anticipated by this examination; the yellow squares symbolize the cancers seen two years later on the mammogram at the end of the trial which are more numerous in the women without the anticipatory MRI. Nevertheless, a comparison of the 'total-cancers' of the two groups clearly shows an excess of cancers for the group with additional MRI.

Now, what happened to those 5.4 excess cancers not found in the non-MRI group, are they cancers that will appear later?

Or have they disappeared?

In general, the explanation put forward is the hyper-slow growth of these cancers, which do not appear during mammography at 2 years of age, not progressing or very very slow  progressing. This would mean that more than half of the cancers found by MRI are hyper-slow-growing cancers so that they are undetectable on mammography. Reminder at 3/30 of the video: we find in the trial 9.8 cancers in the MRI group, 5.4 excess cancers /9.8 total cancers in the MRI group = 0.5

The alternative explanation exists, and it is the cancerous regression, namely the disappearance of these cancers not found on the mammogram for control after two years. They simply disappear. (Editor's note: this hypothesis also emerges from the 2008 Oslo study, where the group of women screened every two years had a 22% excess of cancers detected over the group of women not screened, the two groups being compared after 6 years with a mammogram performed for each group.)

However, if all cancers were inexorably progressing and were expected to manifest themselves, the same number of cancers should be found at the end of the 6-year observation period in regularly screened women and in the non-screened women, in whom the cancers not detected by previous screenings should then be seen on the mammogram at the end of the study, at the end of 6 years. If this is not the case and there is an excess of cancers in the screened group, it is likely that some cancers that did not occur in the unscreened women have disappeared in the meantime.

Cancer regression is observed for other forms of cancer: kidney cancer (1/4 of cancerous lesions regress) of the thyroid (1/3 of cancerous lesions regress). So why not for breast cancer???

The benefit/risk balance

So let's consider the risk/benefit balance of increased MRI monitoring:

video: 6/08.

Overall, the results tends to suggest that the risks associated with increased MRI surveillance of dense breasts outweigh the benefits.

Good news and bad news

There are  good news when it comes to breast cancer. Since the 90s breast cancer mortality has dropped by 40% (i.e. already before the arrival of national screening campaigns, editor's note).

This is an important reduction, according to G.Welsch who reminds us that this drop in mortality is due to therapeutic advances, and not to screening.

Video: 6:20

The bad news according to him is that screening is the target of a technological weapons race, since the first analog mammography, then mammography, the arrival of 3D (tomosynthesis) and now the advent of MRI, all aimed at finding more cancers. For what benefit?

Conclusion of the author

The challenge is not to find more and more cancers inducing unnecessary over-treatment, but to detect those cancers that are important to find because they are a threat to a patient's life.

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


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