Lowering the age of screening? A Pandora’s Box

Comments by Cancer Rose, 17/09/2023

The New USPSTF Mammography Recommendations — A Dissenting View

Steven Woloshin, M.D.,
Karsten Juhl Jørgensen, M.D., D.Med.Sci.,
Shelley Hwang, M.D., M.P.H.,
and H. Gilbert Welch, M.D., M.P.H.

De : Dartmouth Institute and Dartmouth Cancer Center, Lebanon, NH (S.W.); the Lisa Schwartz Foundation for Truth in Medicine, Norwich, VT (S.W., K.J.J., S.H., H.G.W.); Cochrane Denmark and the Center for Evidence-Based Medicine Odense, Department of Clinical Research, University of Southern Denmark, Odense (K.J.J.); the Department of Surgery, Duke University, Durham, NC (S.H.); and the Center for Surgery and Public Health, Department of Surgery, Brigham and Women’s Hospital, Boston (H.G.W.).

https://www.nejm.org/doi/full/10.1056/NEJMp2307229

September 16, 2023

The US Public Health Task Force (USPSTF) issued new recommendations for mammography screening in May 2023, advocating the start of routine mammography at age 40.
This represents a 10-year shift in the recommendations for screening, compared with the previous guidelines, which recommended breast cancer screening starting at age 50 due to the increased risks for younger populations and the limited benefits.

The decision was motivated by two arguments:
-an increase in breast cancers in younger women and
-an increase in the most aggressive cancers in black women.

We have summarized this announcement and the reactions it generated here: https://cancer-rose.fr/en/2023/05/16/lowering-the-age-for-starting-screening-but-at-what-cost/

This change in age recommendations has been widely disputed, particularly on the grounds that it will improve 'equal' treatment for the poorest social classes.
This recommendation is by no means trivial, and the price to be paid by women is likely to be very high, which is why the authors issued a warning yesterday.

Why should this concern us?

Firstly, several recent studies from this year clearly call into question the effectiveness of mammographic screening itself.
No, it doesn't 'save lives' - that myth has long been debunked - and there's no evidence that screenings in general extend lifespan.
No, mammographic screening is not responsible for a reduction in breast cancer mortality; the risk of death from breast cancer is decreasing, whether screening or not.
Breast cancer treatments are improving dramatically, so the value of primary detection is declining, which should make screening obsolete in the future.
No, mammographic screening is not harmless, the harms outweigh the benefits, and overdiagnosis is worse in current assessments.

Secondly, the American recommendations, which are highly advantageous to providers in the women's imaging sector, risk serving as an example and opening a Pandora's box that will then be impossible to close again; voices are already being raised here and there calling even for annual mammography screening...
There's nothing 'conspiracy' about this argument, In fact, breast cancer care is, it must be said publicly, a vast and profitable business, fueled by women's fear of the disease.
This cancer business is what journalist John Horgan explains at length in this article.

Thirdly, a European trial called MyPEBS, has just completed the integration of women allocated to the various study groups.
This study, which is supposed to evaluate individualized screening based on each woman's risk of developing cancer, is clearly calibrated to encourage more and at younger age screening, as it recruits women as young as 40, and includes flagrant biases which we denounced in an open letter along with other health watchdog groups.

Women will not have to choose between screening or no screening but between a standard screening and ... more screening if they are designated “at risk”.
However, the 'low-risk' sub-group will include very few women, and all the others will be assigned to higher-risk sub-groups very quickly, since the software, which has not been scientifically validated, admits very generous risk criteria, and women will be screened more frequently by mammography.
For example, having had a breast biopsy for even a benign lesion is a risk factor, and the number of biopsy procedures in young women for benign lesions such as fibro-adenomas has risen considerably in recent years, making many women de facto "at risk".

In short,

at a time when mammographic screening is struggling to demonstrate any relevance whatsoever, and evidence of its harmfulness is mounting, we are moving both across the Atlantic and in Europe towards more screening, in more young women, with no regard for the risks to which the population is exposed, and of course without informing them.
No one should know....

A Dissenting View

The authors state (excerpts) :

Recently, the U.S. Preventive Services Task Force (USPSTF) changed its recommendation for the starting age for mammography screening from 50 to 40 years.1
Previously, the Task Force deemed screening in 40-to-50-year-old women a personal choice. Because USPSTF recommendations are so influential, mammography screening for women in their 40s will probably become a health care performance measure; if so, it will effectively become a public health imperative with which primary care practitioners must comply. Such a change will affect more than 20 million U.S. women, and it raises some important questions.

First, is there new evidence that mortality from breast cancer is increasing? To the contrary, there has been a steady decrease in breast-cancer mortality in the United States — a major success story of modern medicine.
...
Similar patterns (of mortality reduction) are seen in other high-income countries, including both those where screening of women in their 40s is very rare (Denmark and the United Kingdom) and those where screening is rare in all age groups (Switzerland) — which suggests that the decline has resulted largely from improved treatment, not screening (see graphs).

Second, is there new evidence that the benefit of mammography is increasing? Since the previous USPSTF recommendation was made, there have been no new randomized trials of screening mammography for women in their 40s. Eight randomized trials for this age group, including the most recent (the U.K. Age trial), revealed no significant effect.2
.....
Fast-growing cancers are more likely to be missed by screening, often appearing in the interval between exams......
The USPSTF’s increasing reliance on complex statistical modeling is problematic. Estimated effects can be extremely sensitive to modeling assumptions, which often reflect the conventional wisdom at the time.
.......
So does the balance of benefits and harms support a new public health imperative? Relative risk reductions can be misleading since they contain no information about absolute risk, which is already low and steadily decreasing for this age group. To clarify the potential effects of the updated guideline in absolute terms, the table summarizes the benefits and harms.

.....
In other words, with screening, the likelihood of not dying from breast cancer in the next 10 years increases from 99.7% to 99.8%.
This effect is small, particularly in light of the potential harms and what seem to be overly optimistic assumptions of benefits. By far the most common outcomes are false alarms: the USPSTF model estimates that 36% of women 40 to 49 years of age will have at least one in a 10-year course of biennial screening.......
And some will experience fear: about a third of women describe the experience as “very scary” or “the scariest time of my life.”4....
The harms will be more frequent if screening occurs annually rather than biennially, as is the current practice for most U.S. women.
.....
Given the steadily decreasing mortality over the past 30 years attributable to improved treatments, it’s likely that fewer and fewer women will benefit from screening over time, while more screening will increase the harms.
The Task Force also argues that the new recommendation is an important first step in reducing the disparity between Black and White women in mortality from breast cancer.
....
But it’s hard to imagine how recommending the same intervention to both groups would reduce the disparity, particularly given that screening rates are already similarly high for Black and White women in their 40s......
Nor would earlier screening address the problems facing poor women, who tend to be disproportionately Black, such as the lower quality of medical services available, delayed follow-up on abnormal scans, delays to treatment, and less use of adjuvant therapy. Indeed, lowering the screening age could actually exacerbate the problems contributing to the disparity — by diverting resources toward expanded screening. We need to do more of what really works: ensure that high-quality treatment is more readily accessible to poor women with breast cancer.
.....

It would be better to allow women to make their own decisions based on their own assessment of the data and their values — and to redirect resources to ensuring that all women with breast cancer receive the best and most equitable treatment possible.

References

Preventive Services Task Force. Draft recommendation statement — breast cancer: screening. May 9, 2023 (https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults. opens in new tab).

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

3. Kramer BS, Elmore JG. Projecting the benefits and harms of mammography using statistical models: proof or proofiness? J Natl Cancer Inst 2015;107(7):djv145-djv145.

4. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA 2004;291:71-78.

5. Hayse B, Hooley RJ, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR. Breast cancer biology varies by method of detection and may contribute to overdiagnosis. Surgery 2016;160:454-462.

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8 September 20238 September 2023

Screenings don’t extend lifespan

28/08/2023

Estimated Lifetime Gained With Cancer Screening Tests

A Meta-Analysis of Randomized Clinical Trials

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2808648?guestAccessKey=c7d91084-054d-49f3-97be-9b302f883c9c&utm_source=twitter&utm_medium=social_jamaim&utm_term=11181634494&utm_campaign=article_alert&linkId=232083149

Michael Bretthauer, MD, PhD; Paulina Wieszczy, MSc, PhD; Magnus Løberg, MD, PhDet alMichal F. Kaminski, MD, PhD; Tarjei Fiskergård Werner, MSc; Lise M. Helsingen, MD, PhD; Yuichi Mori, MD, PhD; Øyvind Holme, MD, PhD; Hans-Olov Adami, MD, PhD; Mette Kalager, MD, PhD

JAMA Intern Med. Published online August 28, 2023. doi:10.1001/jamainternmed.2023.3798

This is a systematic review and meta-analysis published by authors from the Institute of Health and Society at the University of Oslo (Norway), examining 18 long-term randomized clinical trials, seeking to estimate the length of life 'gained' through cancer screening.

Several screening tests are analyzed: mammography screening for breast cancer; colonoscopy, sigmoidoscopy, fecal occult blood testing(FOBT) for colorectal cancer; CT screening for lung cancer in current and former smokers; prostate-specific antigen (PSA) testing for prostate cancer.

The study involves 2.1 million people, more precisely 721,718 men for PSA screening, 614,431 men and women for sigmoidoscopy screening, 598,934 men and women for fecal blood testing every two years, 84,585 men and women for colonoscopy screening and 73,634 women for mammography screening ; a smaller sample size for annual fecal blood screening (30,964 men and women) and lung cancer CT screening (20,505 men and women).

The review covers trials with more than 9 years of follow-up (10 to 15 years of follow-up on average) reporting all-cause mortality and estimated acquired life expectancy for 6 commonly used cancer screening tests, comparing 'screening' with 'no screening'.

The endpoint was the duration of life in the 'screening' groups compared with the 'non-screening' groups, based on reported data for all-cause mortality and cancer-specific mortality.

In other words, the years of life "gained" by screening were calculated as the difference in observed lifespan (in person-years) between the "screening" and "non-screening" groups.
The analysis focused on the general population.

MEDLINE and Cochrane Library databases were used as the basis for this search.
Observational and modelling studies were not included due to multiple potential biases.

Key points and main results :

Question: Cancer screening tests are promoted to save lives, but to what extent is life actually prolonged by commonly used cancer screening tests?

Answer: The results of this meta-analysis suggest that colorectal cancer screening by sigmoidoscopy can prolong life by around 3 months; the gain in life span for other screening tests seems unlikely or uncertain.

In this figure, horizontal arrows illustrate four people who underwent screening.
Arrows pointing to the right: 2 people who benefited from screening live longer thanks to early cancer detection and cure.
Arrows pointing to the left: 2 people who suffered screening-related harm and died earlier than those who were not screened.
The blue circle shows the effect of screening on population longevity, calculated as the sum of all individual benefits minus all individual harms.

We can see that, overall, there is no net gain in life expectancy, which is what screening promised when the national campaigns were launched.

Lifetime gains

The authors write: “Based on the observed relative risks for all-cause mortality and the reported follow-up time in the trials, the only screening test that significantly increased longevity was sigmoidoscopy, by 110 days (95% CI, 0-274 days) (Table 2..).
We found no statistically significant outcomes for longevity with mammography screening (0 days; 95% CI, −190 to 237 days) and FOBT screening with yearly or biennial screening (0 days; 95% CI, −70.7 to 70.7 days).
Colonoscopy screening (37 days; 95% CI, −146 to 146 days) and PSA screening (37 days; 95% CI, −37 to 73 days) may have an association with longevity of about 5 weeks, and lung cancer screening among smokers or former smokers of about 3 months (107 days; 95% CI, −286 to 430 days), but these estimates are uncertain (Table 2..)“

Right: life "gained"; left: life "lost".

Diamond dots indicate point estimates of days of life gained or lost for each screening test. Left and right arrows indicate the 95% confidence interval.
CT stands for computed tomography for lung cancer, FOBT for faecal occult blood test, and PSA for prostate-specific antigen.

Discussion

The authors elaborate on their findings.
“Our study quantifies whether use of 6 commonly used cancer screening tests is associated with length of life. One test (sigmoidoscopy) significantly prolonged life and longevity by 110 days, although the lower bound of the 95% CI extended to 0. Fecal testing and mammography screening did not appear to prolong life in the trials, while estimates for prostate cancer screening and lung cancer screening are uncertain.

In recent decades, organized cancer screening programs have been established in Europe, Canada, the Pacific Islands, and in many countries in Asia. In the US, cancer screening is offered by many institutions and encouraged and reimbursed by most health care payers. Several studies have investigated the association between screening and all-cause mortality.⁶^,²⁸ Few have translated their results to practical and easy-to-grasp estimates for health care professionals and individuals on how much cancer screening may increase life expectancy. Our study provides these estimates."

“Even if we did not observe longer lives in general with 5 of the 6 screening tests, some individuals prolong their life due to these screening tests. Cancer is prevented or detected in an early stage, and the individuals survive screening and subsequent treatment without harms or complications. Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage. Thus, these patients experience a gain in lifetime. “

"However, other individuals experience a lifetime loss due to screening.³⁵^,³⁶ This loss is caused by harms associated with screening or with treatment of screening-detected cancers, for example, due to colon perforation during colonoscopy or myocardial infarction following radical prostatectomy.³⁷^,³⁸
For 5 of the 6 screening tests investigated herein, the findings suggest that most individuals will not have any gain in longevity.
For those who have their longevity altered with screening, the cumulative loss for those who are harmed must be outweighed in duration by the cumulative gain experienced by those who benefit to show unchanged lifetime in individuals who undergo screening compared with those who do not”.
......
“Our study may provide easy-to-understand estimates for prolongation of life attributable to screening that may be used in shared decision-making with individuals who consider undergoing a screening test. Our estimates may also serve to prioritize public health initiatives in comparison with other preventive measures, such as obesity treatment or prevention of cardiovascular disease.²⁸
The lack of increased longevity with screening may also occur due to competing causes of death. Many of the cancers we are screening for share risk factors with more prevalent causes of death, such as cardiovascular and metabolic diseases. A lack of a significant increase in longevity due to cancer screening may therefore be due to death from competing causes at the same time a patient would have died of cancer without screening. A mortality shift from cancer to other causes of death without increased length of life is thus plausible."

“Due to the stigma and the psychological burden, a cancer diagnosis may also cause extra noncancer-specific deaths from suicide, cardiovascular disease, and accidents.⁴¹^,⁴² Also, increased surveillance after cancer screening may increase the risk of other incidental disease, which would not have been detected without screening.⁴³

Adherence to more than 1 screening test may potentially increase longevity. The one study that was available²⁸ does not suggest that there is an additive effect of screening for more than 1 cancer. Although such outcomes are possible, the competing risk of other disease might also outweigh the influence of screening for 2 or more cancer sites on length of life...."

Another concern addressed by the authors is quality of life after cancer:
« In addition to lifetime gained or lost with screening, quality of life is important. Quality-adjusted life-years (QALYs) are difficult to measure and interpret, but recent analyses of QALYs for mammography screening estimates in Norway suggest that net QALY in modern mammography screening in Norway may be negative.²⁹^»

Conclusions and relevance of the study:

The results of this meta-analysis suggest that current evidence does not support the claim that cancer screening tests save lives by extending lifespan, with the possible exception of sigmoidoscopy screening for colorectal cancer.

References

Vanchieri C. National Cancer Act: a look back and forward. J Natl Cancer Inst. 2007;99(5):342-345. doi:10.1093/jnci/djk119PubMed Google Scholar Crossref

Bretthauer M, Kalager M. Principles, effectiveness and caveats in screening for cancer. Br J Surg. 2013;100(1):55-65. doi:10.1002/bjs.8995PubMed Google Scholar Crossref

Woloshin S, Schwartz LM, Black WC, Kramer BS. Cancer screening campaigns—getting past uninformative persuasion. N Engl J Med. 2012;367(18):1677-1679. doi:10.1056/NEJMp1209407PubMed Google Scholar Crossref

Seffrin JR. We know cancer screening saves lives. American Cancer Society Cancer Action Network, October 23, 2009. Accessed May 3, 2020. https://www.fightcancer.org/news/we-know-cancer-screening-saves-lives

Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA. 2004;291(1):71-78. doi:10.1001/jama.291.1.71
Article PubMed Google Scholar Crossref

Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA. 2016;315(23):2595-2609. doi:10.1001/jama.2016.6828
Article PubMed Google Scholar Crossref

Heijnsdijk EAM, Csanádi M, Gini A, et al. All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: a review and modeling study. Cancer Med. 2019;8(13):6127-6138. doi:10.1002/cam4.2476PubMed Google Scholar Crossref

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

Bretthauer M, Løberg M, Wieszczy P, et al. Effect of colonoscopy screening on colorectal cancer incidence and mortality. N Engl J Med. 2022;387:1547-1556. doi:10.1056/NEJMoa2208375PubMed Google Scholar Crossref

10.

Atkin W, Wooldrage K, Parkin DM, et al. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet. 2017;389(10076):1299-1311. doi:10.1016/S0140-6736(17)30396-3PubMed Google Scholar Crossref

11.

Miller EA, Pinsky PF, Schoen RE, Prorok PC, Church TR. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: long-term follow-up of the randomised US PLCO cancer screening trial. Lancet Gastroenterol Hepatol. 2019;4(2):101-110. doi:10.1016/S2468-1253(18)30358-3PubMed Google Scholar Crossref

12.

Segnan N, Armaroli P, Bonelli L, et al; SCORE Working Group. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial–SCORE. J Natl Cancer Inst. 2011;103(17):1310-1322. doi:10.1093/jnci/djr284PubMed Google Scholar Crossref

13.

Holme Ø, Løberg M, Kalager M, et al; NORCCAP Study Group†. Long-term effectiveness of sigmoidoscopy screening on colorectal cancer incidence and mortality in women and men: a randomized trial. Ann Intern Med. 2018;168(11):775-782. doi:10.7326/M17-1441PubMed Google Scholar Crossref

14.

Juul FE, Cross AJ, Schoen RE, et al. 15-Year benefits of sigmoidoscopy screening on colorectal cancer incidence and mortality: a pooled analysis of randomized trials. Ann Intern Med. 2022;175(11):1525-1533. doi:10.7326/M22-0835PubMed Google Scholar Crossref

15.

Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst. 1999;91(5):434-437. doi:10.1093/jnci/91.5.434PubMed Google Scholar Crossref

16.

Scholefield JH, Moss SM, Mangham CM, Whynes DK, Hardcastle JD. Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up. Gut. 2012;61(7):1036-1040. doi:10.1136/gutjnl-2011-300774 PubMed Google Scholar Crossref

17.

Jørgensen OD, Kronborg O, Fenger C. A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. Gut. 2002;50(1):29-32. doi:10.1136/gut.50.1.29PubMed Google Scholar Crossref

18.

Lindholm E, Brevinge H, Haglind E. Survival benefit in a randomized clinical trial of faecal occult blood screening for colorectal cancer. Br J Surg. 2008;95(8):1029-1036. doi:10.1002/bjs.6136PubMed Google Scholar Crossref

19.

Martin RM, Donovan JL, Turner EL, et al; CAP Trial Group. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018;319(9):883-895. doi:10.1001/jama.2018.0154
Article PubMed Google Scholar Crossref

20.

Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027-2035. doi:10.1016/S0140-6736(14)60525-0PubMed Google Scholar Crossref

21.

Lundgren PO, Kjellman A, Norming U, Gustafsson O. Long-term outcome of a single intervention population based prostate cancer screening study. J Urol. 2018;200(1):82-88. doi:10.1016/j.juro.2018.01.080PubMed Google Scholar Crossref

22.

Andriole GL, Crawford ED, Grubb RL III, et al; PLCO Project Team. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104(2):125-132. doi:10.1093/jnci/djr500PubMed Google Scholar Crossref

23.

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(6):503-513. doi:10.1056/NEJMoa1911793PubMed Google Scholar Crossref

24.

Wille MM, Dirksen A, Ashraf H, et al. Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling. Am J Respir Crit Care Med. 2016;193(5):542-551. doi:10.1164/rccm.201505-1040OCPubMed Google Scholar Crossref

25.

Paci E, Puliti D, Lopes Pegna A, et al; the ITALUNG Working Group. Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial. Thorax. 2017;72(9):825-831. doi:10.1136/thoraxjnl-2016-209825PubMed Google Scholar Crossref

26.

Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366. doi:10.1136/bmj.g366PubMed Google Scholar Crossref

27.

Tabar L, Fagerberg G, Duffy SW, Day NE. The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit. J Epidemiol Community Health. 1989;43(2):107-114. doi:10.1136/jech.43.2.107PubMed Google Scholar Crossref

28.

Pinsky PF, Miller EA, Zhu CS, Prorok PC. Overall mortality in men and women in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. J Med Screen. 2019;26(3):127-134. doi:10.1177/0969141319839097PubMed Google Scholar Crossref

29.

Zahl PH, Kalager M, Suhrke P, Nord E. Quality-of-life effects of screening mammography in Norway. Int J Cancer. 2020;146(8):2104-2112. doi:10.1002/ijc.32539PubMed Google Scholar Crossref

30.

Helsingen LM, Vandvik PO, Jodal HC, et al. Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. BMJ. 2019;367:l5515. doi:10.1136/bmj.l5515PubMed Google Scholar Crossref

31.

Jodal HC, Helsingen LM, Anderson JC, Lytvyn L, Vandvik PO, Emilsson L. Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta-analysis. BMJ Open. 2019;9(10):e032773. doi:10.1136/bmjopen-2019-032773PubMed Google Scholar Crossref

32.

Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis. BMJ. 2018;362:k3519. doi:10.1136/bmj.k3519PubMed Google Scholar Crossref

33.

Schünemann HJ, Lerda D, Quinn C, et al; European Commission Initiative on Breast Cancer (ECIBC) Contributor Group. Breast cancer screening and diagnosis: a synopsis of the European Breast Guidelines. Ann Intern Med. 2020;172(1):46-56. doi:10.7326/M19-2125PubMed Google Scholar Crossref

34.

National Lung Screening Trial Research Team. Lung cancer incidence and mortality with extended follow-up in the National Lung Screening Trial. J Thorac Oncol. 2019;14(10):1732-1742. doi:10.1016/j.jtho.2019.05.044PubMed Google Scholar Crossref

35.

Saquib N, Saquib J, Ioannidis JPA. Does screening for disease save lives in asymptomatic adults? systematic review of meta-analyses and randomized trials. Int J Epidemiol. 2015;44(1):264-277. doi:10.1093/ije/dyu140PubMed Google Scholar Crossref

36.

Newman DH. Screening for breast and prostate cancers: moving toward transparency. J Natl Cancer Inst. 2010;102(14):1008-1011. doi:10.1093/jnci/djq190PubMed Google Scholar Crossref

37.

Steele RJC, Brewster DH. Should we use total mortality rather than cancer specific mortality to judge cancer screening programmes? no. BMJ. 2011;343:d6397. doi:10.1136/bmj.d6397PubMed Google Scholar Crossref

38.

Penston J. Should we use total mortality rather than cancer specific mortality to judge cancer screening programmes? yes. BMJ. 2011;343:d6395. doi:10.1136/bmj.d6395PubMed Google Scholar Crossref

39.

Whitlock EP, Williams SB, Burda BU, Feightner A, Beil T. Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms; A Systematic Evidence Review for the US Preventive Services Task Force (Evidence Synthesis Number 132). Agency for Healthcare Research and Quality; 2015.

40.

Carlsson LMS, Sjöholm K, Jacobson P, et al. Life expectancy after bariatric surgery in the Swedish Obese Subjects Study. N Engl J Med. 2020;383(16):1535-1543. doi:10.1056/NEJMoa2002449PubMed Google Scholar Crossref

41.

Lu D, Andersson TM, Fall K, et al. Clinical diagnosis of mental disorders immediately before and after cancer diagnosis: a nationwide matched cohort study in Sweden. JAMA Oncol. 2016;2(9):1188-1196. doi:10.1001/jamaoncol.2016.0483
Article PubMed Google Scholar Crossref

42.

Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med. 2012;366(14):1310-1318. doi:10.1056/NEJMoa1110307PubMed Google Scholar Crossref

43.

Shen Q, Lu D, Schelin ME, et al. Injuries before and after diagnosis of cancer: nationwide register based study. BMJ. 2016;354:i4218. doi:10.1136/bmj.i4218PubMed Google Scholar Crossref

44.

Hernán MA, Robins JM. Per-protocol analyses of pragmatic trials. N Engl J Med. 2017;377(14):1391-1398. doi:10.1056/NEJMsm1605385PubMed Google Scholar Crossref

16 June 20233 July 2023

The risk of death from breast cancer is declining, with screening or not

Breast cancer mortality in 500 000 women with early invasive breast cancer in England, 1993-2015: population based observational cohort study

BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-074684 (Published 13 June 2023)

Cite this as: BMJ 2023;381:e074684

Carolyn Taylor, professor of oncology and honorary clinical oncologist1 2,
Paul McGale, statistician1,
Jake Probert, statistician1,
John Broggio, cancer analytical lead3,
Jackie Charman, senior cancer analyst3,
Sarah C Darby, professor of medical statistics1,
Amanda J Kerr, systematic reviewer1,
Timothy Whelan, radiation oncologist4,
David J Cutter, senior clinical research fellow and clinical oncologist1 2,
Gurdeep Mannu, lecturer in general surgery1,
David Dodwell, senior clinical research fellow and clinical oncologist1 2

¹Nuffield Department of Population Health, University of Oxford, Oxford, UK
²Oxford University Hospitals, Oxford, UK
³National Disease Registration Service (NDRS), NHS England, Birmingham, UK
⁴Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON Canada

June the 16th, 2023

Aim of the study

This is an observational cohort study (a group of subjects followed for the duration of the study) involving 512,447 women.

There are two objectives:

1°- Assessment of annual breast cancer mortality rates and cumulative risks by time since diagnosis for women diagnosed during each of the following calendar periods: 1993-99, 2000-04, 2005-09, and 2010-15.

2°- Examination of variations in these mortality rates according to several criteria: according to the calendar period of diagnosis, according to the time elapsed since diagnosis, according to whether or not the cancer was detected by screening, and according to the characteristics of the patients and the tumours they presented.

Overall, almost half the cancers in women in the age groups eligible for screening were detected by screening.

Main results:

Crude risks of breast cancer mortality decreased with increasing calendar period.

In other words, women in calendar periods closer to our contemporary period are more likely to survive long after a cancer diagnosis than women diagnosed in calendar periods further back in time, with a significant magnitude.

The cumulative five-year mortality risk from breast cancer was :

- 14.4% for women diagnosed between 1993 and 1999, and
- 4.9% for women diagnosed between 2010 and 2015.

These results correspond to the entire cohort of 512,447 women aged 18-89, including :
-women eligible for screening, with cancer detected as part of organized screening: 128,240 women (i.e., around a quarter of the cohort)
-women eligible for screening but not screened, with cancer detected outside screening: 133,427 women (i.e., around a quarter of the cohort)
-women not eligible for organized screening: 250,780 women (around half the cohort).

The composition of groups is shown in Table 1, extracted below:

Adjusted annual breast cancer mortality rates also decreased similarly with the advancing calendar period in almost all patient groups, by a factor of around three for estrogen receptor-positive cancers, which correspond to forms of cancer with a better prognosis, and by around two for estrogen receptor-negative cancers, which correspond to more pejorative forms of cancer. The mortality risk improves with the advancement of the calendar periods studied towards more recent years than earlier years.

The study's main aim was to use five-year breast cancer mortality risks for newly diagnosed patients. Indeed, say the authors, these mortality rates, which are now known, can be used to estimate breast cancer mortality risks for today's patients.

The study aims to inform patients and clinicians of the likely absolute mortality risks for patients treated for breast cancer today, considering, among other things, the characteristics of their tumor.

The study shows that, for women diagnosed with early breast cancer, the risk of dying within five years fell considerably between the 1990s and 2010-2015. For most newly diagnosed women, the risk of dying from breast cancer within five years was 3% or less. This is helpful information for women living today.

The authors conclude, "It should be noted, however, that the improvements in breast cancer mortality observed in women whose cancer was detected by screening were paralleled in women whose cancer was not detected by screening."

Detailed conclusions:

The prognosis for women with early invasive breast cancer has improved considerably since the 1990s. Most can expect to survive cancer in the long term, although the risk remains appreciable for a few.

Since the 1990s, the five-year cumulative risk of death from breast cancer has fallen from 14.4% to 4.9% overall, with reductions observed in almost all patient groups.
Indeed, the five-year cumulative mortality risk was 14.4% (95% confidence interval 14.2% to 14.6%) for women diagnosed between 1993 and 1999 and gradually decreased with increasing calendar period to 4.9% (from 4.8% to 5.0%) for women diagnosed later, between 2010 and 2015.
This shows that breast cancer mortality rates decreased with the calendar period of diagnosis over the study period.

But although decreases occurred in almost all patient groups, the magnitude of the mortality rate decreased, and the 5-year risk of cancer death varied considerably between women with different characteristics:
- the risk of mortality was less than 3% for 62.8% of women,
- but 20% or more for 4.6%, corresponding to particularly aggressive forms of cancer that are difficult to cure.

In our data," explain the authors, "the lack of mortality reduction in women aged 80 to 89 with estrogen receptor-negative breast cancer may be explained by the fact that these women generally do not receive systematic adjuvant treatment (treatment that complements the main treatment to prevent the risk of local recurrence or metastases, e.g., hormone therapy or immunotherapy), or radiotherapy, so any improvement in these treatments per se would not have affected mortality in this group of patients. ), or those who do not receive radiotherapy, so any improvement in these treatments per se would not affect mortality in this group of patients.
Patients under 40 years of age at diagnosis had a higher risk of breast cancer mortality than those diagnosed at 40, which is explained by the fact that breast cancers in younger women are inherently more aggressive than those in older women.

The authors found that breast cancer mortality always decreased as a function of the calendar period of diagnosis, irrespective of differences in tumour characteristics, and even the improvements in breast cancer mortality observed in women whose cancer was detected by screening were accompanied by improvements also in those whose cancer was not detected by screening.

This is summarized in the illustration below, which presents the results for all women (a quarter of whom are eligible and screened, a quarter are cancer cases in eligible but unscreened women, and half are women not eligible for screening):

F1 Télécharger

It can be argued that screening has enabled the detection of smaller and smaller tumors over the years with significant technological improvements in mammography equipment, with tumors found of ever lower grades, but, say the authors, this decline in mortality cannot be attributed to changes in tumor size, number of positive nodes or tumor grade alone, as breast cancer mortality continued to decline according to the calendar period of diagnosis, even after adjusting for these factors.

Furthermore, screening and more sensitive breast imaging techniques are likely to have led only to earlier diagnosis and longer survival without altering the clinical course of the disease. Survival, it should be remembered, corresponds to the duration of life after cancer diagnosis and increases with improved treatment and overdiagnosis. The earlier in a person's life cancers are detected that were not destined to kill their host anyway, that are very low-grade and will remain so, the more survival data are artificially improved, without affecting life expectancy.

Relationship with screening

For patients diagnosed with screened or unscreened cancer, annual breast cancer mortality rates and cumulative breast cancer mortality risks showed similar downward trends to those for all women, depending on the calendar period of diagnosis.

The study shows that the improvements in breast cancer mortality observed in women whose cancer was detected by screening were also paralleled by improvements in those whose cancer was not detected by screening.
The increase in screening does not, therefore, explain the improvements in mortality.

The contribution of the study

Other studies have already shown the very marginal role of screening in the decline in breast cancer mortality since the 1990s.
We already know that the risk of breast cancer mortality following early invasive breast cancer diagnosis has decreased over the last few decades.

Bleyer and Miller's impact study concluded that the link between screening mammography and the degree of reduction in breast cancer mortality observed in recent years was increasingly controversial. Their comparison of eight countries in Europe and North America showed no correlation between the intensity of national screening and the timing or even the extent of reduction in breast cancer mortality.

The evidence from the three different approaches (temporal approach, magnitude approach, and comparative approach with other non-screened pathologies) and other additional observations did not support the hypothesis that mammography screening was the main reason for the reduction in breast cancer mortality observed in Europe and North America.

Similarly, P.Autier's study of the three pairs of countries compared suggested that screening had not played a direct role in reducing breast cancer mortality, given the contrast between the temporal differences in the implementation of mammographic screening and the similarity in mortality reductions between the pairs of countries.
In other words, countries that introduced screening earlier than other countries that introduced it later experienced a similar reduction in breast cancer mortality. In contrast, there should have been an amplifying phenomenon in mortality reduction due to the earlier introduction of campaigns. There is, therefore, no link between screening activity and reduced mortality.

And invasive metastatic cancer remains at the same level, as screening is unable to detect this aggressive form of cancer because of its intrinsic biologically aggressive characteristics and often because of its high velocity.

To conclude, we quote this study: Søren R Christiansen, Philippe Autier, Henrik Støvring, Change in effectiveness of mammography screening with decreasing breast cancer mortality: a population-based study.
Summarized here.

According to the authors, improvements in cancer therapies over the past 30 years have reduced mortality, which could erode the benefit-disadvantage balance of mammography screening.
Furthermore, future improvements in managing breast cancer patients will increasingly reduce the benefit-harm ratio of screening.
The benefit of mammography in terms of mortality reduction is diminishing, while the harms, such as overdiagnosis, are constant.
Screening leads to both over-diagnosis and over-treatment, at both human and economic costs,

What the study here provides is an estimate of the extent of the decline in breast cancer mortality rates observed since the 90s, and this is not linked to screening or any other factor related to the tumor or the woman carrying cancer since there is no difference in variations in mortality rates whatever these factors may be, whether the cancer is found by screening or not.
The reason for this is most likely to be found in the therapeutic improvements of recent decades.

Illustration: annual mortality rates and cumulative mortality risks

F2 Télécharger

Cumulative risk is the sum of the various annual risks, present over 5 years. The mortality risk function describes the evolution as a function of time and cumulative factors of the instantaneous risk of death.

Summary by Cancer Rose

This is a descriptive epidemiological study. It aims to quantify the reduction in mortality observed since the 90s. This reduction is not a scoop, but it was interesting to quantify it globally and by sub-group.
It ranges from 14.4% to 4.9% at 5 years between the two periods examined, for all women, with a similar reduction depending on the group (screened or not).

Studies of the impact of screening (see our article) have already demonstrated this reduction in breast cancer mortality since the 90s. Still, the impact of screening is very marginal, or even non-existent, since this reduction is not synchronized with the introduction of screening campaigns.

In essence, the authors conclude that recent data show an improvement in breast cancer mortality risk compared with older data, which is confirmed by their results. They make several points: "... Therefore, increases in screening cannot solely explain the decreases in breast cancer mortality that we observed” and a little further on: " this observational study cannot determine the specific causes of these reductions in mortality.
And yet again, probably the most important: "... Notably, however, the improvements in breast cancer mortality seen in women with screen-detected cancers were paralleled by improvements in those whose cancers were not screen-detected.”

This study confirms (and, above all, quantifies) the downward trend in breast cancer mortality, but it does not conclude (nor does it enable us to conclude) the cause(s) of this decline.

What's important to understand is that in this study, we're not talking about the mortality rate but the cumulative RISK of mortality over 5, 10, or 15 years. These cumulative mortality risks depend on the time T0 chosen. Here, T0 is the date of cancer diagnosis. Therefore, the mortality risks presented in the study are influenced by the lead time (since T0 will be earlier for screened cancers than for unscreened cancers). They will give an apparent better success rate in the screened groups.
Lead-time bias is a well-known inherent bias in screening, giving the illusion of better cancer survival when we've just anticipated its 'date of onset'.

The prognosis for breast cancers is improving, but it is impossible to say how much of this is due to screening, therapeutic advances, and confounding factors such as early diagnosis bias, overdiagnosis in particular, and social and economic factors.

According to the studies already available (see article), the role of screening is probably marginal, and apparent success in screened groups is influenced by lead time.

Rapid responses in BMJ

Dr Vincent Robert is our statistician.

Per-Henrik Zahl is researcher on the Norwegian Institute of Public Health

https://www.bmj.com/content/381/bmj-2022-074684/rapid-responses

Opinion

Risk of breast cancer death after a diagnosis of early invasive breast cancer

BMJ 2023; 381 doi: https://doi.org/10.1136/bmj.p1355 (Published 13 June 2023)Cite this as: BMJ 2023;381:p1355

Mairead MacKenzie, patient advocate1,
Hilary Stobart, patient advocate1,
David Dodwell, senior clinical research fellow and clinical oncologist2 3,
Carolyn Taylor, professor of oncology and honorary clinical oncologist2 3

¹Independent Cancer Patients’ Voice
2. ²Nuffield Department of Population Health, University of Oxford
3. ³Oxford University Hospitals, Oxford, UK

Two patient advocates reflect on how they helped to shape a research study into breast cancer

Mairead MacKenzie and Hilary Stobart were diagnosed with breast cancer some years ago. They’re just two of the half a million women who contributed their data to our study of women diagnosed with early breast cancer in England. As patient advocates, they also helped to shape the study.

Hilary and Mairead both feel that up-to-date information is needed on outcomes after a diagnosis of early breast cancer. They used their expertise as patients to highlight how data from women diagnosed with breast cancer in the past could help in the clinic today. Moreover, the study also gave them a chance to reflect on all that has changed since they were diagnosed with cancer.

“You don't have much grasp of having cancer until you've had it,” explains Hilary. “You suddenly join a club that you don't want to be part of, and you find you have an awful lot in common with the other people in the club. You have a different perspective on what's important.”

Our study was informed by that perspective.

The study provides risk estimates for individual patients. Both Hilary and Mairead stress that doctors need to help patients understand that breast cancer is “not all one thing.” Prognosis varies widely according to risk factors such as tumour size, lymph node involvement and whether the tumour was detected by screening.

“When I was diagnosed 20 years ago, I was not given a prognosis other than the fact that this is serious and we need to treat you quickly,” says Mairead. “But I think good, clear communication about prognosis can make a vast difference to a patient's quality of life, and how they can cope with things.”

“When people are diagnosed with breast cancer they may already know somebody who has died from breast cancer,” adds Hilary. “They might assume that their risk is the same, but many of them might only have less than 1% risk of dying from breast cancer at five years.”

“For the majority of women, the prognosis is good,” agrees Mairead. “This study backs that up and gives reassurance—because, initially, everybody thinks they're going to die.”

The study shows that, for women diagnosed with early breast cancer, the risk of dying from it within five years reduced substantially between the 1990s and 2010-15. For most women diagnosed recently their five year risk of breast cancer death was 3% or less.

Breast cancer patients have contributed to that improvement.

“I’ve yet to meet a cancer patient who isn’t happy for their data to be used for research,” says Mairead. “If there's a chance of doing something that might make it easier for those coming after, patients nearly always say yes.”

“And if people hadn't said yes, we wouldn't be where we are now, would we?” agrees Hilary “We know our treatment now is good because of all the work that was done earlier …the large numbers of trials and the thousands of women who were prepared to go into them.”

Our results are part of that legacy. They quantify decades of improvements and lay the foundation for more to come. Meanwhile, they can inform how doctors talk with patients about their prognosis today.

“It’s good news,” concludes Hilary. “It shows what we’ve done, and that we need to go on doing it. More studies like this one will be needed in the future. Breast cancer is still with us. There’s a lot more to do.”

18 May 202318 May 2023

Screening for…cytoliosis!

The impact of influences in a medical screening programme invitation: a randomized controlled trial

May 7, 2023, BY CANCER ROSE

Christian Patrick Jauernik 1,2, Or Joseph Rahbek 1,2, Thomas Ploug 3, Volkert Siersma 1, John Brandt Brodersen 1,2
1 Department of Public Health, The Research Unit for General Practice and Section of General Practice, University of Copenhagen, Copenhagen, Denmark
2 The Primary Health Care Research Unit, Zealand Region, Sorø, Denmark
3 Centre for Applied Ethics and Philosophy of Science, Department of Communication and Psychology, Aalborg University Copenhagen, Copenhagen, Denmark
European Journal of Public Health, ckad067, https://doi.org/10.1093/eurpub/ckad067

The authors of this publication had the idea of screening for a fictitious disease, "cytoliosis," non-transmissible and potentially fatal, and sent out invitations for screening using pamphlets, which were also fictional.
This trial is randomized with seven arms, i.e., seven groups of people in a total of 600 people studied. Each group received a pamphlet with messages that differed to a greater or lesser extent in their incentive to participate in screening.

The objectives of the study were:
1) to assess whether the different methods of influence had a significant effect on the intention to participate in a screening program, and
2) to assess whether participants were aware of these influences and whether there was a relationship between intention to participate and awareness.

Introduction and background

According to the authors:

"Screening programs for different cancers are implemented in many developed countries. They have intended benefits, including a reduction in mortality and morbidity plus less radical treatments.1"
However, cancer screening programmes come with many unintended harms such as false-positive results, overdiagnosis and overtreatment, possibly leading to physical, psychological or social harms.2 The quality of screening programmes is sometimes evaluated by a considerable participation rate.3–5"

From the perspective of health authorities, it is assumed that a cancer screening program is more beneficial than harmful, and that a high participation rate would maximize the expected benefits of the screening program. In addition, citizens with lower socioeconomic status are found to have a higher incidence of cancer diseases (except breast cancer) but are less likely to participate in screening programs.

“This creates another incentive for health authorities to make screening participation barrier-free and simple to promote equality in health. The healthcare authorities can systematically influence citizens in subtle ways that may increase participation rates without making the choice to participate adequately informed.”

« Not all citizens will share the same assessment of the benefits/harms as the health authorities. And even if they agree with the health authorities that the benefits outweigh the harms on a population level, they may still not wish to participate because they on an individual level might receive more harm than benefit—current evidence suggests that the more informed citizens are less likely to participate in cancer screening.10,11 »

The authors refer to a study published in 2019 on the methods of influence health authorities use to push populations to participate in various screening programs. These methods range from anxiety-provoking messages to minimizing the risks and harms of screening.
Our French National Cancer Institute (INCa) was cited in this study in the categories of 1) Misrepresentation of statistics and 2) Unbalanced representation of harm versus benefit.

It is amusing, by the way, that said INCa is very keen to classify the screening controversy as fake news on a page titled "enlightenment" while itself being caught at fault for manipulating the public with its biased and misleading documentation. The author of this 2019 study on public manipulation is a co-author of this current study; in 2019, he distinguished in his publication 5 categories of people's influences:
1.      Tendentious presentation of statistics Biased presentation of statistics,
2.     Omission of harmful effects and emphasis on benefits,
3.     Recommendations of participation,
4.     Opt-out systems -This consists of assigning citizens a pre-determined appointment at the time of the invitation. If the person does not wish to participate, the person must actively opt-out. The patient's non-refusal is considered de facto acceptance to participate.
5.     Fear appeals.

These types of influences significantly affect individual participation by circumventing or thwarting reflection and may be incompatible with informed decision-making.

Cytoliosis

This disease created for the study, supposedly deadly, was invented to avoid a bias due to preconceived ideas and fears related to cancer.

“The pamphlet for screening for cytoliosis (i.e. 'the neutral') was partially based on the Danish colorectal cancer (CRC) screening pamphlet, and cytoliosis shared the same incidence and mortality as CRC.17 The screening programme for cytoliosis shared the same benefits (e.g., mortality reduction) and harms (e.g., false positives, physical harm, and overtreatment) as CRC screening for a 50–60-year-old male. The harms of the fictitious screening programme were increased compared with CRC screening to better balance the benefits and harms of participation.”

Seven different brochures were distributed, one for each of the seven groups in this randomized study:
A- The "neutral" pamphlet
B- A pamphlet with relative risk reductions to accentuate the reduction in mortality.
( Similar to the INCa process for breast cancer, giving percentages of mortality reduction that correspond to comparison rates between populations, but not at all to the real, absolute data.
This technique of misleading in the presentation of mortality reduction is constantly used by INCa, even though the citizens criticized it during the citizens consultation on breast cancer screening in 2016; nothing has changed in the communication of INCa, and we can still read in the documents a "20% mortality reduction", which corresponds in real life to a single woman whose life is prolonged by screening on women 2000 screened and on 10 years of screening, which is no longer the same thing ....)
C- The third pamphlet misrepresented the harms versus the benefits, omitting the harmful effects and emphasizing the benefits, again very similar to INCa's methods with deliberate omission of the most important risks,(read https://cancer-rose.fr/en/2021/10/23/inca-still-outrageously-dishonest-and-unethical-2/)
D- The fourth pamphlet was based on pre-booked appointments (opt-out system, see above)
E- The fifth pamphlet contained an explicit recommendation to participate
F- The sixth pamphlet appealed to fear
G- And finally, a last pamphlet contained all the influence systems at the same time.

All the types of influence studied were inspired by real examples of cancer screening programs (pamphlets 2 and 4 for our French institute)

All the pamphlets can be found in the PDF appendix

The results

A- Main result: a measure of intention to participate

"The lowest proportion of people intending to participate (31.8%) was observed in the group that received the neutral pamphlet (A), while the proportion of people with the intention to participate ranged from 39.2% to 80.0% when the other, non-neutral pamphlets were distributed.."

See Table 2

Intention to participate (without adjustment for socio-demographic status) increased statistically significantly in groups that received brochures containing relative risk reductions (B), misrepresentation of harms versus benefits (C), an explicit recommendation to participate (E), fear appeals (F), and all influences combined(G)

B- Secondary outcome: awareness of influences and effect of awareness of influences on intention to participate

Were participants aware of the influences they were subject to participate more, and was there a relationship between intention to participate and this awareness of the influences experienced?
"A majority ranging from 60.0% to 78.3% of participants," the authors say, "reported no awareness that their choice was attempting to be influenced (pamphlets B through G).
There was no clear difference between responses to the neutral brochure (A) and the pamphlets containing a deliberate attempt to influence participants' choice."
"Participants who received a pamphlet with influence (B-G) and did not indicate awareness that their choice was influenced had a higher intention to participate than those who felt the pamphlet was trying to influence their choice and then correctly located an influence."

The authors also say that participants with an influential pamphlet who were unaware of this had more intention to participate than those who felt the pamphlet was trying to direct their choice but failed to locate the influence correctly.

Nevertheless, the authors warn that "Secondary outcomes should be interpreted cautiously. Because secondary outcomes are measured after participants have indicated their intention to participate, this may affect their response about whether the pamphlet was trying to guide their choice. We hypothesize that participants who intended to participate may be more reluctant to admit they were potentially influenced."

In any case, it is certain and demonstrated that the five categories of influence increase intention to participate when used in materials sent to screening targets.
Less than half of the participants recognized these influences, and not knowing about them was de facto associated with an increase in intention to participate.

Author's conclusion

"These results call for reflection and discussion on using different types of influence to increase participation rates in cancer screening programs. The potential risks of participation in cancer screening programs can be serious and substantial, and the intended effect of increasing participation rates through the use of influences must be carefully weighed against the unintended effect of potentially circumventing participants' informed choice.

Thus, there is a need to find alternative ways to evaluate cancer screening programs besides participation rates.
One such alternative could be the rate of informed decisions made by potential screening participants."

This is even though, as the authors speculate, citizens might feel helpless upon learning about the multiple risks of screenings.

Other aspects in a person's decision-making to participate or not are also to be considered:
"Information material is not the only aspect of decision making, and this study does not examine external reasons for participants' choices, e.g., society's (health) culture, society's own and general attitudes toward health interventions, sense of duty, behavior, and opinions of significant others, barriers to intention and actual behavior, financial incentives of health professionals to increase screening uptake, etc. ...Research on external reasons can quantify the importance of decision making on information materials."
"The considerable effect of influences that are further reinforced by unawareness (of these influences) suggests that the application of these influences should be carefully considered for interventions where informed participation is intended."

The editors of this publication suggest that further research into the potential negative effects of these influences be considered, as the negative effects of these influence techniques on the population result in a weakening of trust in health authorities.

APPENDIX-PAMPHLETS

Pamphlets Télécharger

Cancer Rose Commentary

This publication, along with Rahbek's from 2019, is another reminder of the disastrous effects on people's health of the harmful influences that misleading and unbalanced information materials can cause.

It should always be kept in mind that materials for screenings are sent to populations that are doing well and have, a priori, no clinical complaints. The influence used to get them into potentially harmful screening processes is akin to imposing a potentially harmful health device without informing and deceiving people. This is ethically indefensible, yet done by health authorities.

The French INCa is cited in this 2019 study, as can be seen in a summary table of the study (https://cancer-rose.fr/wp-content/uploads/2021/04/nouveau-tableau.pdf; see highlighted parts); rather than devoting resources to pointing the finger at a growing controversy about the relevance of breast cancer screening, the institute would do well to devote time and resources to correcting its serious communication flaws that mislead French citizens on breast cancer screening.

Concerning breast cancer screening, we can put this study in relation to another one, a French one, published in 2016, showing that when women are given a little more objective information about breast cancer screening by mammography, they participate less.(https://cancer-rose.fr/en/2021/01/24/objective-information-and-less-acceptance-of-screening-by-women/ )

This study went relatively unnoticed, and for a good reason, since for the health authorities, only one criterion counts, that is the uptake, the misleading of women is a fully assumed scientific theme. (https://cancer-rose.fr/en/2020/12/17/manipulation-of-information/)

References of the study

Références

1 Brodersen J, Jorgensen KJ, Gotzsche PC. The benefits and harms of screening for cancer with a focus on breast screening. Polskie Archiwum Medycyny Wewnetrznej 2010;120:89–94.

2 Jorgensen KJ. Mammography screening. Benefits, harms, and informed choice. Dan Med J 2013;60:B4614.

3 Public Health England. Health matters: Improving the prevention and diagnosis of bowel cancer. 2016. Available at: https://www.gov.uk/government/publications/health-matters-preventing-bowel-cancer/health-matters-improving-the-prevention-and-detection-of-bowel-cancer (15 January 2020, date last accessed).

4 The Danish Health Agency. Screening for cervical cancer – recommendations. [Danish] 2012. Available at: http://www.sst.dk/~/media/B1211EAFEDFB47C5822E883205F99B79.ashx (15 January 2020, date last accessed).

5 The Danish Health Agency. Screening for colorectal cancer – recommendations. [Danish] 2012. Available at: https://www.sst.dk/~/media/1327A2433DDD454C86D031D50FE6D9D6.ashx (1 February 2020, date last accessed).

6 Broberg G, Wang J, Östberg AL, et al. Socio-economic and demographic determinants affecting participation in the Swedish cervical screening program: a population-based case-control study. PLoS One 2018;13:e0190171.

7 Orsini M, Trétarre B, Daurès J-P, Bessaoud F. Individual socioeconomic status and breast cancer diagnostic stages: a French case–control study. Eur J Public Health 2016;26:445–50.

8 Boscoe FP, Henry KA, Sherman RL, Johnson CJ. The relationship between cancer incidence, stage and poverty in the United States. Int J Cancer 2016;139:607–12.

9 Hofmann B, Stanak M. Nudging in screening: literature review and ethical guidance. Patient Educ Couns 2018;101:1561–9.

10 Hersch J, Barratt A, Jansen J, et al. Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: a randomised controlled trial. Lancet 2015;385:1642–52.

11 Hestbech MS, Gyrd-Hansen D, Kragstrup J, et al. Effects of numerical information on intention to participate in cervical screening among women offered HPV vaccination: a randomised study. Scand J Prim Health Care 2016;34:401–19.

12 Rahbek OJ, Jauernik CP, Ploug T, Brodersen J. Categories of systematic influences applied to increase cancer screening participation: a literature review and analysis. Eur J Public Health 2021;31:200–6.

13 Ploug T, Holm S, Brodersen J. To nudge or not to nudge: cancer screening programmes and the limits of libertarian paternalism. J Epidemiol Community Health 2012;66:1193–6.

14 Ploug T, Holm S. Doctors, patients, and nudging in the clinical context–four views on nudging and informed consent. Am J Bioeth 2015;15:28–38. Google ScholarCrossrefPubMedWorldCat

15 Sarfati D, Howden-Chapman P, Woodward A, Salmond C. Does the frame affect the picture? A study into how attitudes to screening for cancer are affected by the way benefits are expressed. J Med Screen 1998;5:137–40.

16 Lönnberg S, Andreassen T, Engesæter B, et al. Impact of scheduled appointments on cervical screening participation in Norway: a randomised intervention. BMJ Open 2016;6:e013728.

17 The Danish Health Agency. Bowel cancer: treatment and prognosis [Danish] 2019. Available at: https://www.sst.dk/da/Viden/Screening/Screening-for-kraeft/Tarmkraeft/Behandling-og-prognose (1 February 2020, date last accessed).

18 Adab P, Marshall T, Rouse A, et al. Randomised controlled trial of the effect of evidence based information on women's willingness to participate in cervical cancer screening. J Epidemiol Community Health 2003;57:589–93.

19 Malenka DJ, Baron JA, Johansen S, et al. The framing effect of relative and absolute risk. J Gen Intern Med 1993;8:543–8.

20 Johansson M, Jorgensen KJ, Getz L, Moynihan R. "Informed choice" in a time of too much medicine-no panacea for ethical difficulties. BMJ 2016;353:i2230.

21 Getz L, Brodersen J. Informed participation in cancer screening: the facts are changing, and GPs are going to feel it. Scand J Prim Health Care 2010;28:1–3.

22 Byskov Petersen G, Sadolin Damhus C, Ryborg Jønsson AB, Brodersen J. The perception gap: how the benefits and harms of cervical cancer screening are understood in information material focusing on informed choice. Health Risk Soc 2020;22:177–96.

23 Hoffmann TC, Del Mar C. Patients' expectations of the benefits and harms of treatments, screening, and tests: a systematic review. JAMA Intern Med 2015;175:274–86.

24 Reisch LA, Sunstein CR. Do Europeans like nudges? Judgm Decis Mak 2016;11:310–25.

25 Slovic P, Peters E, Finucane ML, Macgregor DG. Affect, risk, and decision making. Health Psychol 2005;24:S35–40.

26 Loewenstein GF, Weber EU, Hsee CK, Welch N. Risk as feelings. Psychol Bull 2001;127:267–86.

27 Damhus CS, Byskov Petersen G, Ploug T, Brodersen J. Informed or misinformed choice? Framing effects in a national information pamphlet on colorectal cancer screening. Health, Risk and Society 2018;20:241–58.

18 May 202318 May 2023

Overdiagnosis is underestimated in screenings, a systematic review

Synthesis by Cancer Rose, April 2, 2023

According to this systematic review, randomized cancer screening trials are rarely designed to estimate overdiagnosis. Many trials used in the design of screenings have been biased toward underestimating the degree of overdiagnosis.

This is the first review and re-analysis of overdiagnosis in cancer screening trials.

Several authors (Danish, Portuguese, and Norwegian), including researchers from the Cochrane Collaboration, conducted this review.
Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews
Theis Voss, Mikela Krag, Frederik Martiny, Bruno Heleno, Karsten Juhl Jørgensen, John Brandt Brodersen
https://doi.org/10.1016/j.canep.2023.102352

The strength of this overview is that it included trials from the Cochrane systematic reviews, which are known for their comprehensive literature searches and structured assessment of the risk of bias, and a USPSTF systematic review, with high methodological standards[54]. The search strategy is updated, and the authors have verified the reference list of included trials, which increases the likelihood of presenting a comprehensive and up-to-date overview.
The degree of overdiagnosis in standard cancer screening trials is uncertain because of inadequate trial design, variable definition, and the methods used to estimate overdiagnosis.

The authors sought to quantify the risk of overdiagnosis for the most widely implemented cancer screening programs and to assess the implications of design issues and biases in the trials used for various screenings on estimates of overdiagnosis by conducting a new analysis of systematic reviews of cancer screening.

PubMed and the Cochrane Library were searched from their publication dates through November 29, 2021. The authors assessed the risk of bias using the Cochrane Collaboration's Cochrane Risk of Bias Tool.

Nineteen trials described in thirty articles were identified for review, reporting results for the following types of screening:
*mammography for breast cancer,
*chest x-ray or low-dose CT scan for lung cancer,
*alpha-fetoprotein and ultrasound for liver cancer,
*rectal examination, prostate specific antigen, and transrectal ultrasound for prostate cancer,
*CA-125 test and/or ultrasound for ovarian cancer.

No melanoma screening trials were eligible.

The magnitude of overdiagnosis ranged from 17% to 38% in cancer screening programs. On average, the authors found that:

-27% of breast cancers detected by mammography,
-31% of lung cancers detected by low-dose CT,
-27% of liver cancers detected by screening
-38% of prostate cancers detected by PSA and
-17% of ovarian cancers detected by CA-125

Here is a summary of the significant parts of the article published in Cancer Epidemiology, with tables, followed by Cancer Rose comments (additional figures are at the end).

1. Introduction

Overdiagnosis of cancer is the diagnosis of an indolent neoplastic pathology that would never progress to the point of causing symptoms and/or death during an individual's lifetime[1] and is the most serious harm of cancer screening[2],[3],[4] If a cancer is detected, clinicians cannot know which individuals are overdiagnosed because it is impossible to know how the cancer would have progressed without screening. Therefore, all patients are offered routine treatment or surveillance[5],[6]. Those who are overdiagnosed are therefore unnecessarily diagnosed and then overtreated, which is detrimental to them.

For this reason, knowing the magnitude of overdiagnosis in cancer screening is critical to making informed screening decisions, such as whether to participate individually or to implement a given screening program at the national level, such as prostate cancer screening[7],[8].

In theory, the most robust method for estimating overdiagnosis is to use data from randomized controlled trials with lifetime follow-up of all participants and without contamination of either the control or intervention group, i.e., without screening of both trial groups during and after the end of the study[5],[9]. [At the end of the active screening phase, an excess of cancers in the screened population is expected, as screening should advance the time of diagnosis (lead time) [5]. If there were no overdiagnosis, this excess of cancers should be offset over time, as they would all progress to a cancer that would be clinically detected after the active screening phase.
Thus, a persistent excess in the cumulative incidence of cancer in the screened population after a follow-up period sufficient to account for lead time is high-quality evidence of overdiagnosis[5],[8],[10].

The objective of this overview and re-analysis of systematic reviews of randomized controlled trials of cancer screening was to assess the extent of design limitations and biases in the randomized controlled trials included to quantify overdiagnosis and, if possible, to estimate the likelihood that the cancer detected by screening was overdiagnosed for the most common cancer screening programs. Many, if not all, types of cancer screening can lead to overdiagnosis. To our knowledge, we are the first to compile data on overdiagnosis in screening for different cancers. For this paper, we have chosen to focus on the most common cancer screening programs.

2. Methods used

This overview and re-analysis of systematic reviews was carried out on the basis of a protocol published before the present study was conducted[11].

Eligibility criteria

Systematic reviews of randomized trials were eligible if they:
1) studied screening to detect cancer earlier than it would appear clinically.
2) compared a cancer screening intervention with no screening.
3) reported the incidence of cancer in screened and unscreened participants, and the number of cancers detected by screening.
4) were conducted by the Cochrane Collaboration, i.e., Cochrane reviews, and included only randomized controlled trials. .....
.......

Search strategy

We searched the Cochrane Library of Systematic Reviews (February 2016) using the search terms "screening" and "cancer" in the title, abstract, or keywords.

Risk of bias assessment for included trials

We extracted risk of bias assessments from included Cochrane systematic reviews. We used the Cochrane Risk of Bias Tool version 1.0[14] which includes the following six areas:

1. Selection bias: random sequence generation and allocation concealment
2. Performance bias: blinding of participants and staff (not extracted)
3. Detection bias: blinding of outcome evaluation
4. Attrition bias: incomplete outcome data
5. Reporting bias: selective reporting of outcomes
6. other possible sources of bias
............
We evaluated two additional biases that could affect the estimate of overdiagnosis (Table 1):
1. Control group contamination after randomization[15] Contamination was defined as the reported number of participants in the control group who were exposed to the same screening technology as the screened group. ......
2. Inadequate consideration of time delay (too short post-intervention follow-up or screening offered to the control group at the end of the trial)

Table 1

Other factors influencing estimates of overdiagnosis.
1. Different cancer risk at baseline between intervention and control groups (equivalent to the selection bias included in the Cochrane Risk of Bias tool).
2. Participation rate in screening rounds. Participation was not considered a bias in the estimation of overdiagnosis, but a component of screening.
3. Number of screening cycles and the interval between them.
4. Continuation of screening, i.e., whether participants continued with the proposed screening modality on their own initiative after screening ended.
............

3. Results

Of the 19 trials reviewed, the smallest trial had 3206 participants (ITALUNG [22]), the largest 202,546 participants (UKCTOCS [23]) and the median trial size was 26,602 participants (Stockholm [24]) (Table 2)

Estimates of overdiagnosis in included studies

For all trials and all types of cancer screening programs, estimates of overdiagnosis ranged from 6% to 67%.

* For breast cancer screening trials using mammography, estimates ranged from 10% to 30% .
* For lung cancer by low-dose CT, overdiagnosis ranged from 13% to 67% .
* For prostate cancer, estimates ranged from 12% to 63% .
* In ovarian cancer by CA-125, from 6 to 42%.
Only one trial of liver cancer screening and one trial of lung cancer screening by chest x-ray were included, and both showed that 27% of lung or liver cancers detected by screening were overdiagnosed, respectively (Table 4 and Figure 2 (at the end of the article)).

Click to enlarge

In our primary meta-analysis, we estimated that 28% (95% CI: 4-52%) of screen-detected breast cancers were overdiagnosed using data from the Malmö breast cancer screening trial. This trial had an overdiagnosis rate that was three percentage points higher than the meta-analysis based on all included trials (Table 4, Figure 2, Supplementary Figure A1, see end of article). [28], [29].

Our post hoc meta-analysis of the most reliable trials, i.e., excluding trials with high risk of bias in the areas of random sequence generation, assignment concealment, contamination, or turnaround time, included data from 12 trials reporting outcomes for six types of cancer screening. On average, 27% (95% CI: 8-45%) of breast cancers detected by mammography and 30% (95% CI: 2-59%) of lung cancers detected by low-dose CT were overdiagnosed.

For the other four types of screening, the results were not significant. We estimated that an average of 27% (95% CI -10% to 64%) of lung cancers detected by chest radiography, 27% (95% CI -4% to 58%) of liver cancers detected by screening, and 17% (95% CI -14% to 48%) of ovarian cancers detected by CA-125 are overdiagnosed.......

Meta-analysis of all trials included in the synthesis, regardless of risk of bias, showed that on average, 25% (95% CI 12-38%) of breast cancers detected by mammography, 27% (95% CI -10% to 64%) of lung cancers detected by chest radiography, 29% (95% CI 7-52%) of lung cancers detected by low-dose CT, 27% (95% CI 4%-58%) of liver cancers detected by ultrasound, 38% (95% CI 14-62%) of prostate cancers detected by PSA, 17% (95% CI -14%-48%) of ovarian cancers detected by CA-125, and 6% (95% CI -27%-39%) of ovarian cancers detected by ultrasound were overdiagnosed (Fig. 2, end of article).

4. Discussion

Main results

In our post-hoc meta-analysis of the most reliable trials, that is, excluding trials with a high risk of bias ......we found that:
-27% (95% CI 8-45%) of breast cancers detected by mammography,
-31% (95% CI 2-59%) of lung cancers detected by low-dose CT,
- 27% (95% CI -4% to 58%) of liver cancers detected by screening and
-17% (95% CI -14% to 48%) of ovarian cancers detected by CA-125 were overdiagnosed.

Many trials were at risk of bias because of poor randomization, control group contamination, or inadequate consideration of waiting time, i.e., insufficient follow-up time to account for slow-growing cancers.
Confidence in the estimates of overdiagnosis further decreased because of imprecision in the pooled estimate and inconsistency (heterogeneity) between trials (Figure 2, Supplementary Table A1, end of article).

Implications for Practice

Overdiagnosis is the most serious drawback of cancer screening.

Yet we found that many screening trials for various types of cancer were not adequately designed to estimate its magnitude. Many screening programs have been implemented on the basis of preliminary beneficial results. However, the adverse effects of screening, such as overdiagnosis, take many years to be adequately estimated. This overview underscores the need for continued evaluation (by the USPSTF, for example) of current and future cancer screening programs to take into account potential adverse effects that may require modifications or even termination of a screening program.

5. Conclusion

Randomized controlled trials are the most reliable model for quantifying overdiagnosis if they are designed for that purpose; however, our overview shows that confidence in estimates of overdiagnosis in randomized controlled trials of cancer screening is moderate to very low.
.................
Two screening technologies (lung cancer by low-dose CT and breast cancer by mammography) showed significant overdiagnosis of 30% and 27%, respectively.

In addition, for prostate cancer screening with PSA, the estimate suggests that 38% of screen-detected prostate cancers were overdiagnosed, although the risks of bias are high in the included randomized clinical trials, which favors underestimation.

For ovarian cancer screening programs, our best estimates are that 17% of ovarian cancers screened by CA-125 and 6% of ovarian cancers screened by transvaginal ultrasound may be overdiagnosed.

Additional Figures

Click on the image to enlarge

FIG 1

FIG A1

FIG 2

Comments Cancer Rose

Three issues must be raised:

-First, regarding information for women, the National Cancer Institute's information documents remain insufficient and deficient in exposing complete data. Only the lowest ranges are disclosed to women, and overdiagnosis is largely minimized.
https://cancer-rose.fr/en/2022/10/20/the-new-inca-2022-booklet-on-breast-cancer-screening/

-The risks of breast cancer screening outweigh, when added to false alarms, morbidity and mortality secondary to overtreatment (hemopathies, cardiopathies, and cancers secondary to treatment), radiation-induced cancers, and the hypothetical benefit of this screening, treatments being recognized to be the cause of the relative decrease in mortality since the 1990s.
Therefore it is scandalous that the scientific controversy about this screening is, according to the French National Cancer Institute, among the "fake news."

A study on risk-stratified screening is financed to the tune of 12 million euros, which will be unable to quantify the over-diagnosis of breast cancer screening, giving women a choice between a (standard) screening and another (stratified) screening based on the principle that breast cancer screening must be maintained, and this in disregard of the demands of the citizens during the public consultation on breast cancer screening.
However, the fundamental question is: should we maintain these expensive screenings, most of which are services of little value to the population?

Another screening has not been addressed in this analysis because it is officially non-existent, that of thyroid cancer, which is widely practiced by systematic cervical ultrasound, despite a known and frightening risk of overdiagnosis (up to 84%!!!), and which is mainly borne by women.
In addition to the cost of human health, its economic cost in France was the subject of a study published in 'Value in Health'.
Here are the results:
Between 2011-2015, an estimated 33,911 women and 10,846 men in France were diagnosed with thyroid cancer, with an average cost per capita of €6,248.
Of those treated, 8,114-14,925 women and 1,465-3,626 men were treated due to overdiagnosis. The total cost of care for thyroid cancer patients was €203.5 million (€154.3 million for women and €49.3 million for men).

Overdiagnosis represents a clinical problem for the individual and a public health problem for the population not only in France but in the Western world, but also a colossal economic burden.

References of the study

[1] J. Brodersen, L.M. Schwartz, S. Woloshin, Overdiagnosis: how cancer screening can turn indolent pathology into illness, Apmis 122 (8) (2014) 683–689.

[2] B. Heleno, M.F. Thomsen, D.S. Rodrigues, K.J. Jørgensen, J. Brodersen, Quantification of harms in cancer screening trials: literature review, Bmj 347(2013) f5334.

[3] K.J. Jørgensen, P.-H. Zahl, P.C. Gøtzsche, Overdiagnosis in organised mammography screening in Denmark. A comparative study, BMC Women’S. Health 9 (1) (2009) 36.

[4] Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement, Ann. Intern. Med. 164 (4) (2016) 279–296.

[5] H.G. Welch, W.C. Black, Overdiagnosis in cancer, J. Natl. Cancer Inst. 102 (9) (2010) 605–613.

[6] H.G. Welch, S. Woloshin, L.M. Schwartz, L. Gordis, P.C. Gøtzsche, R. Harris, et al., Overstating the evidence for lung cancer screening: the International Early Lung Cancer Action Program (I-ELCAP) study, Arch. Intern Med 167 (21) (2007) 2289–2295.

[7] J.L. Carter, R.J. Coletti, R.P. Harris, Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods, Bmj 350 (2015) g7773.

[8] C. Biesheuvel, A. Barratt, K. Howard, N. Houssami, L. Irwig, Effects of study methods and biases on estimates of invasive breast cancer overdetection with mammography screening: a systematic review, Lancet Oncol. 8 (12) (2007) 1129–1138.

[9] P.C. Gøtzsche, K.J. Jørgensen, Screening for breast cancer with mammography, Cochrane Database Syst. Rev. 2013 (6) (2013), Cd001877.

[10] R. de Gelder, E.A. Heijnsdijk, N.T. van Ravesteyn, J. Fracheboud, G. Draisma, H.J. de Koning, Interpreting overdiagnosis estimates in population-based mammography screening, Epidemiol. Rev. 33 (1) (2011) 111–121.

[11] T. Voss MK, B. Heleno, K.J. Jørgensen, F. Martiny, J. Brodersen. Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews. crdyorkacuk/prospero/. 2019.

[12] Team TE Endnote. EndNote X9 ed. Philadelphia, PA: Clarivate; 2013.

[13] Corporation M.. Microsoft Excel. Microsoft Exel, Microsoft 365. 2018 ed: Microsoft Corporation; 2018.

[14] Higgins J.P.T. AD, Sterne JAC. Assessing risk of bias in included studies: The Cochrane Collaboration; 2011 [updated updated March 2011. 5.1.0 [Available from: www.cochrane-handbook.org.

[15] J. Brodersen, How to conduct research on overdiagnosis. A keynote paper from the EGPRN May 2016, Tel Aviv, Eur. J. Gen. Pr. 23 (1) (2017) 78–82.

[16] D. Ilic, M. Djulbegovic, J.H. Jung, E.C. Hwang, Q. Zhou, A. Cleves, et al., Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis, BMJ 362 (2018) k3519.

[17] J. Brodersen, Overdiagnosis: An Unrecognised and Growing Worldwide Problem in Healthcare, Zdr. Varst. 56 (3) (2017) 147–149.

[18] M.G. Marmot, D.G. Altman, D.A. Cameron, J.A. Dewar, S.G. Thompson, M. Wilcox, The benefits and harms of breast cancer screening: an independent review, Br. J. Cancer 108 (11) (2013) 2205–2240.

[19] Team RC. R: A Language and Environment for Statistical Computing. 2013.

[20] Review Manager (RevMan) 5.3 ed. Copenhagen:: The Nordic Cochrane Centre. The Cochrane Collaboration; 2014.

[21] M. Johansson, J. Brodersen, P.C. Gøtzsche, K.J. Jørgensen, Screening for reducing morbidity and mortality in malignant melanoma, Cochrane Database Syst. Rev. 6 (6) (2019), Cd012352.

[22] E. Paci, D. Puliti, A. Lopes Pegna, L. Carrozzi, G. Picozzi, F. Falaschi, et al., Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial, Thorax 72 (9) (2017) 825–831.

[23] U. Menon, A. Gentry-Maharaj, M. Burnell, N. Singh, A. Ryan, C. Karpinskyj, et al.,Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial, Lancet 397 (10290) (2021) 2182–2193.

[24] A. Kjellman, O. Akre, U. Norming, M. T¨ornblom, O. Gustafsson, 15-year followup of a population based prostate cancer screening study, J. Urol. 181 (4) (2009) 1615–1621.

[25] A.B. Miller, T. To, C.J. Baines, C. Wall, Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years, J. Natl. Cancer Inst. 92 (18) (2000) 1490–1499.

[26] Miller A.B., To T., Baines C.J., Wall C.. The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002;137(5 Part 1):305–12.

[27] A.B. Miller, C. Wall, C.J. Baines, P. Sun, T. To, S.A. Narod, Twenty five year followup for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ, Br. Med. J. 348 (2014) g366.

[28] I. Andersson, L. Janzon, Reduced breast cancer mortality in women under age 50:updated results from the Malm¨o Mammographic Screening Program, J. Natl. Cancer Inst. Monogr. 22 (1997) 63–67.

[29] S. Zackrisson, I. Andersson, L. Janzon, J. Manjer, J.P. Garne, Rate of over-diagnosis of breast cancer 15 years after end of Malm¨o mammographic screening trial: follow-up study, Bmj 332 (7543) (2006) 689–692.

[30] S. Shapiro, Evidence on screening for breast cancer from a randomized trial, Cancer 39 (6) (1977) 2772–2782.

[31] S. Shapiro, Periodic Screening for Breast Cancer: The HIP Randomized Controlled Trial, JNCI Monogr. 1997 (22) (1997) 27–30.

[32] S. Moss, I. Thomas, A. Evans, B. Thomas, L. Johns, Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years, Br. J. Cancer 92 (5) (2005) 949–954.

[33] S.M. Moss, H. Cuckle, A. Evans, L. Johns, M. Waller, L. Bobrow, Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’follow-up: a randomised controlled trial, Lancet 368 (9552) (2006) 2053–2060.

[34] S.M. Moss, C. Wale, R. Smith, A. Evans, H. Cuckle, S.W. Duffy, Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years’ follow-up: a randomised controlled trial, Lancet Oncol. 16 (9)(2015) 1123–1132.

[35] P.C. Prorok, P. Wright, T.R. Riley, B.S. Kramer, C.D. Berg, J.K. Gohagan, Overall and Multiphasic Findings of the Prostate, Lung, Colorectal and Ovarian (PLCO) Randomized Cancer Screening Trial. Rev Recent Clin Trials 13 (4) (2018) 257–273.

[36] Oken M.M., Hocking W.G., Kvale P.A., Andriole G.L., Buys S.S., Church T.R., et al. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial Differences in risk for type 1 and type 2 ovarian cancer in a large cancer screening trial. JAMA. 2011;306(17):1865–73.

[37] Z. Saghir, A. Dirksen, H. Ashraf, K.S. Bach, J. Brodersen, P.F. Clementsen, et al., CTscreening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with lowdose CT, Thorax 67 (4) (2012) 296–301.

[38] H.J. de Koning, C.M. van der Aalst, P.A. de Jong, E.T. Scholten, K. Nackaerts, M.A. Heuvelmans, et al., Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial, N. Engl. J. Med 382 (6) (2020) 503–513.

[39] U. Yousaf-Khan, C. van der Aalst, P.A. de Jong, M. Heuvelmans, E. Scholten, J.W. Lammers, et al., Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval, Thorax 72 (1) (2017) 48–56.

[40] U. Pastorino, M. Rossi, V. Rosato, A. Marchian`o, N. Sverzellati, C. Morosi, et al.,Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial, Eur. J. Cancer Prev. 21 (3) (2012) 308–315.

[41] U. Pastorino, M. Silva, S. Sestini, F. Sabia, M. Boeri, A. Cantarutti, et al., Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy, Ann. Oncol. 30 (7) (2019)1162–1169.

[42] S. Gonz´alez Maldonado, E. Motsch, A. Trotter, H.U. Kauczor, C.P. Heussel,S. Hermann, et al., Overdiagnosis in lung cancer screening: Estimates from the German Lung Cancer Screening Intervention Trial, Int J. Cancer 148 (5) (2021)1097–1105.

[43] B.H. Zhang, B.H. Yang, Z.Y. Tang, Randomized controlled trial of screening for hepatocellular carcinoma, J. Cancer Res Clin. Oncol. 130 (7) (2004) 417–422.

[44] J. Hugosson, M.J. Roobol, M. Månsson, T.L.J. Tammela, M. Zappa, V. Nelen, et al.,A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer, Eur. Urol. 76 (1) (2019) 43–51.

[45] G. Sandblom, E. Varenhorst, O. L¨ofman, J. Rosell, P. Carlsson, Clinical consequences of screening for prostate cancer: 15 years follow-up of a randomised controlled trial in Sweden, Eur. Urol. 46 (6) (2004) 717–723.

[46] G. Sandblom, E. Varenhorst, J. Rosell, O. Lofman, P. Carlsson, Randomised prostate cancer screening trial: 20 year follow-up, Bmj 342 (2011) d1539.

[47] G.L. Andriole, E.D. Crawford, R.L. Grubb 3rd, S.S. Buys, D. Chia, T.R. Church, et al.,Mortality results from a randomized prostate-cancer screening trial, N. Engl. J.Med 360 (13) (2009) 1310–1319.

[48] G.L. Andriole, E.D. Crawford, R.L. Grubb 3rd, S.S. Buys, D. Chia, T.R. Church, et al.,Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up,J. Natl. Cancer Inst. 104 (2) (2012) 125–132.

[49] P.F. Pinsky, E. Miller, P. Prorok, R. Grubb, E.D. Crawford, G. Andriole, Extended follow-up for prostate cancer incidence and mortality among participants in the Prostate, Lung, Colorectal and Ovarian randomized cancer screening trial, BJU Int 123 (5) (2019) 854–860.

[50] S.M. Temkin, E.A. Miller, G. Samimi, C.D. Berg, P. Pinsky, L. Minasian, Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival, in: European journal of cancer (Oxford, England: 1990), 87, 2017, pp. 182–188.

[51] I.J. Jacobs, S.J. Skates, N. MacDonald, U. Menon, A.N. Rosenthal, A.P. Davies, et al., Screening for ovarian cancer: a pilot randomised controlled trial, Lancet 353 (9160) (1999) 1207–1210.

[52] S.W. Duffy, D. Vulkan, H. Cuckle, D. Parmar, S. Sheikh, R.A. Smith, et al., Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial, Lancet Oncol. 21 (9) (2020) 1165–1172.

[53] G. Sandblom, E. Varenhorst, J. Rosell, O. L¨ofman, P. Carlsson, Randomised prostate cancer screening trial: 20 year follow-up, BMJ 342 (2011) d1539.

[54] Force USPST. [Available from: https://www.uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/procedure-manual/proceduremanual-section-4-evidence-review-development.

[55] Pollock M.F.R., Becker L.A., Pieper D., Hartling L. Chapter V: Overviews of Reviews. Available from www.training.cochrane.org/handbook.2022.

[56] P.H. Zahl, K.J. Jørgensen, P.C. Gøtzsche, Overestimated lead times in cancer screening has led to substantial underestimation of overdiagnosis, Br. J. Cancer 109 (7) (2013) 2014–2019.

[57] S.W. Duffy, D. Parmar, Overdiagnosis in breast cancer screening: the importance of length of observation period and lead time, Breast Cancer Res 15 (3) (2013) R41.

[58] R. Gulati, E.J. Feuer, R. Etzioni, Conditions for Valid Empirical Estimates of Cancer Overdiagnosis in Randomized Trials and Population Studies, Am. J. Epidemiol. 184(2) (2016) 140–147.

[59] Deeks J.J.H.J., Altman D.G. (editors). Chapter 10: Analysing data and undertaking meta-analyses. Chapter 10: Analysing data and undertaking meta-analyses. Available from www.training.cochrane.org/handbook.2022.

[60] M. Johansson, F. Borys, H. Peterson, G. Bilamour, M. Bruschettini, K.J. Jørgensen, Addressing harms of screening - A review of outcomes in Cochrane reviews and suggestions for next steps, J. Clin. Epidemiol. 129 (2021) 68–73.

[61] R. Manser, A. Lethaby, L.B. Irving, C. Stone, G. Byrnes, M.J. Abramson, et al., Screening for lung cancer, Cochrane Database Syst. Rev. 2013 (6) (2013), Cd001991.

[62] D. Ilic, M.M. Neuberger, M. Djulbegovic, P. Dahm, Screening for prostate cancer, Cochrane Database Syst. Rev. (1)) (2013).

[63] Siu A.L. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine; 2016. [Accessed October 2016] Available from https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breast-cancer-screening1?ds=1&s=breast%20cancer%20screening.

[64] Moyer V.A. Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine; 2013. [accessed October2016] Available from: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening?ds=1&s=lung%20cancer%20screening. [.

[65] Moyer V.A.. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine; 2012. [Accessed October2016] Available from https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/prostate-cancer-screening?ds=1&s=prostat%20cancer%20screening.

[66] M.W. Marcus, S.W. Duffy, A. Devaraj, B.A. Green, M. Oudkerk, D. Baldwin, et al.,Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial, Thorax 74 (8) (2019) 761–767.

[67] A. Hodkinson, J.J. Kirkham, C. Tudur-Smith, C. Gamble, Reporting of harms data in RCTs: a systematic review of empirical assessments against the CONSORT harms extension, BMJ Open 3 (9) (2013), e003436.

[68] J.P. Ioannidis, S.J. Evans, P.C. Gotzsche, R.T. O’Neill, D.G. Altman, K. Schulz, et al., Better reporting of harms in randomized trials: an extension of the CONSORT statement, Ann. Intern Med 141 (10) (2004) 781–788.

28 January 202328 January 2023

Stage 0 DCIS Saga

Stage 0 DCIS Saga — Guest Blog by Lynn Good

Published with the kind permission of Donna Pinto, author of the DCIS411 blog, and Lynn Good, author of the testimonial, from United States

Thanks Donna and Lynn!

Posted on January 25, 2023 by Donna Pinto

Thank you for this blog; it has been a great help to me.

My family doctor pressed me to get a mammogram a couple of months ago. I am 70 years old and had had a mammogram 16 months before. There is no history of breast cancer in my family. After the mammogram, the radiology center asked me to come back for more imaging because they thought they saw something of concern. The results of the second, more detailed scan showed some calcifications; the radiologist showed me images and said I could choose between monitoring and having a biopsy; she said the calcifications were near the chest wall so she wasn’t sure a biopsy would get them. I said I was comfortable waiting. At that point she started putting on a lot of pressure for me to choose to have a biopsy instead. I agreed, expecting it would be negative. The procedure required 3 tries, the third time with a larger needle, to get the desired sample. A clip was placed to mark the location. The results of the biopsy came back Ductal Carcinoma in Situ (DCIS), ER+, left breast, Stage 0. My family doctor then referred me for a follow-up MRI of both breasts and to a surgeon and oncologist. The MRI was done and showed nothing. NOTHING! Both the radiologist and my family physician talked about the likelihood that a lumpectomy would take care of the DCIS; my doctor said Tamoxifen or another estrogen suppressant might be prescribed to address the estrogen sensitivity shown in the biopsy pathology results. Neither mentioned the clean MRI.

At the surgery consult, the surgeon began by showing knowledge of my medical history, which seemed to show she had done her homework, then gave us an opportunity to ask questions. I asked about sentinel node biopsy based on information my brother, whose wife died of breast cancer, gave me; she said she would be doing that using blue dye to find the nodes. She wanted an RFID clip inserted in place of the one the radiologist had put in. She also described how she decided by how the tissue “felt,” how much of the breast she would remove. Pathology would be done on the sample afterward to help decide on further treatment. While I was focused on this, my husband mentioned a lumpectomy; the surgeon corrected him, telling us that that wasn’t the correct term-the procedure was technically called a “modified radical mastectomy,” but I didn’t absorb that part of the conversation. Later at home, my husband brought it up, saying that he thought that meant removal of the entire breast. (By the way, his first wife died of breast cancer and he has told me over our years together what that was like, so I am not unfamiliar with what cancer can do to a person.) At that point I became upset. The next day, a Friday, I left a message asking the surgeon to call me to clarify whether she was planning breast conservation or to remove the entire thing. As she was in surgery that day, I was told she would not be able to call back until Monday. Later that day, her assistant called and gave me the dates for the surgery and all of the other related procedures.

Over the weekend, I tried to find information on what a “modified radical mastectomy” was; I think I had heard her say it, but thought the “modified” meant it would be a lumpectomy. What I found told me it wasn’t. It also told me what the surgery would do to my body and how that might feel. And I came across a number of articles, in journals and reputable publications, about the overtreatment of DCIS with surgery. That DCIS doesn’t always progress. I also found this website [DCIS 411]. After a great deal of anguish and talking it over with my husband, I realized I was more afraid of having my body mutilated and myself traumatized by the surgical procedure and the prospect of living the rest of my life from scan to scan wondering whether it would be clean or not, than I was of actually dying! As I said, I am 70 years old, and I have had a very good life. I also have begun to have some health challenges that even before this, led me to begin thinking about end-of-life issues because, you know what? We all die eventually!

By the end of the weekend, I knew that I was not going to go ahead with the surgery, at least not now. I’m even a bit uncomfortable with the idea of a second opinion or monitoring, because I expect to just be pushed back toward this treatment treadmill. I will go back to see my family doctor and try to explore other options, none of which, you notice, have been presented to me yet, or information on pros and cons of options and descriptions of the possible/likely outcomes of alternatives. I don’t know if there are practitioners in my area that would consider other approaches or respect my values and right to choose, but I am going to try to find one.

As I was approaching my 70^th birthday recently, I felt I have reached the normal human lifespan; I can feel ways my body is beginning to break down. But today, I am still here, and every day that that is true is a gift. I choose to experience that in an intact body, not one that is mutilated and with a mind that is traumatized and kept terrified by the prospect of a negative scan or medical report in the future and what will have to be done to me to treat it. And I am prepared to live with the consequences of that choice.

I am sure that my decision is not necessarily right for others; situations are different, everyone has to decide for themselves, and no one really knows what it feels like to walk in another person’s shoes.

Donna's reply:

Thank you Lynn for sharing your story and insights. I’m so happy you have found help and solace from DCIS 411. Wishing you peace, love, light and health – Donna Pinto

For anyone interested in writing a guest blog post, please email me (Donna) at dp4peace@yahoo.com

30 October 202230 October 2022

Increase of cancers, an epidemic?

Dr. C.Bour, October 27, 2022

Marie Négré Desurmont is a journalist and lecturer who studied anthropology at École des Hautes Études in Paris in Social Sciences. She is a science journalist who has studied specifically on the subject of breast cancer after being affected herself and being struck, as Maëlle Sigonneau was, by the injunctions towards patients conveyed by language and that they have to face in their daily lives.

In a dedicated piece titled "Pink October or the Non-politics of the Breast," the author denounces what she calls the pink month's neutralization of social, environmental, and political issues. She advocates for a broader vision beyond the simple Pink October campaign to ensure a healthy future for the following generations.
"Let us have the courage to look beyond Pink October and require that we bring into the world little girls who won't have to waste so much energy trying to survive, cared for by the same world that made them sick," she writes.

She denounces:
"...rather than politicizing this serious disease, we prefer to repeat that it is best-treated cancer. We focus on individual behaviors by valuing the survivors who have learned so much from this difficult experience.."
The emphasis is placed, with a colorful and smiling veneer, on appearance and well-being "because," the author writes, quoting Audre Lordre (Cancer Journal*), "it is easier to demand that people be happy than to clean up the environment. Let's look for joy, shouldn't we, instead for healthy food, clean air, and a less crazy future on livable earth ."

*Audre Lorde, Journal du Cancer, translated from the American by Frédérique Pressman, Éd. Mamamélis, Geneva, 1998.

Cancer Politicization

In her book "Impatiente," Malle Sigonneau already called for a fight that must go beyond focusing exclusively on the particular behaviors of "survivors."
For her, it would be necessary to boycott Pink October, replacing pink messages with large posters on endocrine disruptors; we could imagine a month, she wrote, where we would 'sensitize' (to use an overused and meaningless word) on the carcinogenic effects of the environment, for example, pesticides...

Mrs. Desurmont sums up our society's attitude very well: "Our society has so much faith in its technological capabilities that it is more concerned with fixing the damage of growth than with creating another form of production and exchange, less mortifying."

Behavioral and environmental factors are responsible for almost half of all cancers. The author correctly points out that risk factors include not only tobacco, alcohol, or obesity but also endocrine disruptors, ionizing radiation (including mammography! ), air pollution, new chemicals (pesticides), exhaust fumes, occupational exposures, and general population exposure to chemical substances.

The pink campaigns and health authorities' messaging speak little about it. "By trying to make us believe that we are masters of our health, impenetrable to the surrounding conditions, and independent of our societal structures, we patients begin to anxiously seek the origin of our illness, psychologizing this sickness at any costs."

We talk about the injustice of a disease that hits women in their absolute femininity, but according to Desurmont, " What is unfair is what we have done to the world, not cancer that just can take advantage of the red carpet we roll out for it to thrive."
The reality is that by talking about injustice and little individual battles, we convince ourselves that cancer is anecdotal, that it's "poor luck," and that all it takes to beat it is a strong spirit. However, it is not a rosy epidemic and worsens as the environment deteriorates. Ladies, adopt a healthy lifestyle, but remember that while you jog, you breathe contaminated air."

Marie Négré Desurmont, like Malle Sigonneau, rightly condemns the guilt and responsibility put on cancer patients.

But what about the "epidemic"?

An epidemic?

What if the "epidemic" also came from medicine?

In his book "Dépistage du cancer du sein, la grande illusion" (ed.Souccar), Bernard Duperray explains:
"From the 1980s to the 2000s, the number of mammograms performed exploded. At the same time, the number of senographs, the devices used to perform mammograms, increased considerably: from 308 senographs in 1980 with 350,000 mammograms in 1982 to 2,511 senographs with 3 million mammograms in 2000. What was the result of this spectacular increase in mammography activity? 21,387 breast cancers were diagnosed in 1980, 42,696 in 2000, and 49,087 in 2005. An epidemic of breast cancer? Is epidemic independent of human activity or the result of uncontrolled human activity?
EPIDEMIC OR OVERDIAGNOSIS LINKED TO SCREENING ACTIVITY?
Two hypotheses can be considered to explain this surge of cancers:

-either it is a simple coincidence between the introduction of screening and the onset of a breast cancer epidemic

- or it is a plethora of breast cancer diagnoses linked to screening.

Let's look at the first hypothesis. If the continuous increase in new diagnoses each year corresponds to an epidemic of progressive cancers, the reduction in mortality due to screening would have to be considerable. There would be 1 cured cancer for every 1 death in 1980 and 3 cured cancers for every 1 death in 2000.
Neither the most optimistic results of randomized trials regarding mortality reduction, nor the therapeutic advances during this period, can support this hypothesis.

Let's look at the second scenario, in which screening is the cause of the increase in the number of new cases of cancer diagnosed each year.
Between 1980 and 2000, the incidence rate increased by an average of 2.7% per year. The increase affected all age groups but was most pronounced among women aged 50 to 75. This is the age group for which systematic mammography screening is performed (in the ten pilot departments). ......

The current epidemic of breast cancer is only apparent. Why apparent? Without screening, many of the cancers diagnosed today would not have occurred. With the overdiagnosis generated by screening, we are thus creating an only visible epidemic. When we admit to overdiagnosis, an increase in incidence does not imply an epidemic.
There is no concrete counterargument to the concept of increased overdiagnosis associated with screening. "Demonstrating its reality is based on indisputable epidemiological data and reliable facts."

I give a detailed explanation in my book "mammo ou pas mammo" (ed.Souccar), which I share with you here:
"A study has been conducted in France to allow this analysis of the situation: it is a survey conducted in 2011 by international epidemiologists, including a Frenchman, Bernard Junod, a prominent epidemiologist from the École des Hautes études en santé Publique de Rennes (EHESP) (Junod B, et al. S. An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts. BMC Cancer. 2011;11(1):1-8. ).

Their observations are as follows:

- ✹ The number of mammography machines in operation in France increased steadily over 20 years, from 308 in 1980 to 499 in 1984, 1351 in 1990, 2282 in 1994, and 2511 in 2000. The number of devices has thus increased eightfold between 1980 and 2000. As a result, screening has intensified.
- ✹ When the incidence of breast cancer at different times in women of the same age group is compared, it increases over time. It is significantly higher when women are intensively screened. The most significant increase, 112%, occurred in 2005 for the 60-64 age group.
Thus, this increase in breast cancer incidence has occurred in parallel with the rise in screening intensity, as illustrated in Figure 1.

As screening increases, so does incidence. This increasing incidence rate as soon as the systematic screening is introduced is striking. It has been observed in all countries where screening has been introduced. "

The denunciation of the failure to consider environmental factors is entirely justified and relevant. Still, the role of medicine must be included and denounced in the same way.
We must ask ourselves the right questions in the face of an increase in new cases of cancer. The simultaneous absence of a reduction in serious cancers, the consequent lack of a reduction in these cancers that kill, that screening does not detect because they cannot be anticipated and evolve with a growth rate that makes them serious cancers. Incidence is increasing. Mortality is not falling in parallel with the intensity of screening.

At the same time, massive and systematic screening finds a plethora of tumors that would never have killed if undetected, a phenomenon known as overdiagnosis. Carcinomas in situ are a substantial source of overdiagnosed cancers and, according to some scientists, are wrongly labeled as cancers.

Why is overdiagnosis a real danger?

It excessively increases the incidence (the rate of new cancer cases) of breast cancer; as these are cancers that would never have been harmed, survival rates are artificially improved, leading to the reassuring slogan: "breast cancer is very well treated and often cured." Of course, it is cured all the better because we over-treat lesions that should never have been detected and would never have killed anyway. The medical profession cannot refrain from telling patients that they have been "saved," whereas screening may have harmed them.

Above all, overdiagnosis leads to overtreatment, which includes radiation therapy. Radiotherapy treatments, like breast surgery (partial and total mastectomies), which is not "lightened," contrary to what health authorities state, are only rising, contributing to what our two authors decry, namely exposure to ionizing radiation.
It is likely that the issue here is not so much the direct exposure during mammography (except for young, non-menopausal women under 50 years old who have an increased risk of radiation-induced cancer) as the treatment that a woman receives.
Speaking of "light" treatment, as the health authorities do, appears cynical because the issue is not one of the lightening therapies but of ensuring that women are not overdiagnosed and do not receive abusive therapy that they should not have had.

Radiation toxicity, downplayed in breast cancer screening, is a reality; radiation-induced cancer should not be ignored.
Radiation-induced heart disease is the biggest killer in survivors of treated cancer.
Hematological cancers can occur after radiation and chemotherapy.

Experiencing this is not harmless; sharing it abusively because a woman has not been alerted to the risk of overdiagnosis inherent in screening is ethically unacceptable.

Conclusion

So yes, let's return to Ms. Desurmont's conclusion: "Let's have the courage to look beyond Pink October and demand that we be able to bring into the world little girls who won't have to waste so much energy trying to survive, cared for by the same world that made them sick."

But this courage must include questioning medicine and how it makes healthy people sick by making them go through tests, they don't need.

This is what the public, the sick and the healthy, and especially the politicians need to be "made aware of." And this is done by telling women the truth about the risks and benefits of screening, not by using pink propaganda that wrongly makes women heroes when some of them should never have known they had this disease and others have this disease in its most serious form, which makes them invisible, impoverishes them, and isolates them from society.

26 September 202226 September 2022

The irreversibility of screening

Dr. C.Bour, September 26, 2022

A short history

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

1° Prostate cancer screening

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

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

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

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

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

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

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

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

2° breast cancer screening

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

3-Bronchopulmonary cancer screening.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A HAS opinion on the relevance of screening

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

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

2- A reliable test

3- Effective treatments against the disease must exist

4- People at risk must be identifiable

5- Screening must be known to decrease cancer mortality.

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

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

1- Early detection of disease before symptoms.

For breast and prostate, not always...

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

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

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

2- Reliability of the test

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

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

3-Effective treatments

Yes

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

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

4-Identifiable persons at risk.

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

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

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

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

5-Decrease in mortality

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

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

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

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

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

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

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

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

==> in total:

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

And nevertheless...

...the European Commission proposes at the end of 2022 an extension and/or a resumption of certain screenings and the implementation of new ones.
The objective is that by 2025, 90% of the EU population will be screened for breast, prostate, cervical, and colorectal cancer.
In addition, lung and stomach cancer screening will be included, although no conclusive studies exist for the latter.

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

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

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

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

Conclusion

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

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

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

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

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

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

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

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

References

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

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

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

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

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

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

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

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

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

12 September 202212 September 2022

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).

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

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

8 September 20228 September 2022

Cancer screening for older adults; a bad idea

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

Jenna Smith¹², Rachael H Dodd¹², Karen M Gainey², Vasi Naganathan³, Erin Cvejic², Jesse Jansen¹²⁴, Kirsten J McCaffery¹²

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

Objective of the study:

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

Method:

21 studies were included.

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

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

Results:

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

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

Cancer Rose commentary

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

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

A study from the University of Leyden provides an answer.

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

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

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

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

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

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

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

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

Conclusion

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

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

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

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

Glasgow-communication

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

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

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

Session Description:

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

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

The New USPSTF Mammography Recommendations — A Dissenting View

Why should this concern us?

In short,

A Dissenting View

References

Estimated Lifetime Gained With Cancer Screening Tests

A Meta-Analysis of Randomized Clinical Trials

Key points and main results :

Lifetime gains

Discussion

Conclusions and relevance of the study:

References

Breast cancer mortality in 500 000 women with early invasive breast cancer in England, 1993-2015: population based observational cohort study

Aim of the study

Main results:

Detailed conclusions:

Relationship with screening

The contribution of the study

Illustration: annual mortality rates and cumulative mortality risks

Summary by Cancer Rose

Rapid responses in BMJ

Opinion

The impact of influences in a medical screening programme invitation: a randomized controlled trial

Introduction and background

Cytoliosis

The results

A- Main result: a measure of intention to participate

B- Secondary outcome: awareness of influences and effect of awareness of influences on intention to participate

Author's conclusion

APPENDIX-PAMPHLETS

Cancer Rose Commentary

References of the study

Références

1. Introduction

2. Methods used

Eligibility criteria

Search strategy

Risk of bias assessment for included trials

3. Results

Estimates of overdiagnosis in included studies

4. Discussion

Main results

Implications for Practice

5. Conclusion

Comments Cancer Rose

References of the study

Cancer Politicization

An epidemic?

Why is overdiagnosis a real danger?

Conclusion

A short history

1° Prostate cancer screening

2° breast cancer screening

3-Bronchopulmonary cancer screening.

A HAS opinion on the relevance of screening

1- Early detection of disease before symptoms.

2- Reliability of the test

3-Effective treatments

4-Identifiable persons at risk.

5-Decrease in mortality

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

==> in total:

And nevertheless...

Conclusion

References

A-too many diagnoses:

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

C- Diagnoses made too early:

Why is this harmful?

A- over-diagnosing...

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

C-Too early diagnosis,

Other examples cited in the article:

Conclusion

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

A call from Canadian scientists

Conclusion of the call:

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

Objective of the study:

Method:

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