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.

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

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

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.

16 May 202316 May 2023

Lowering the age for starting screening, but at what cost?

May 15, 2023, by Cancer Rose

As reported by the Globe and Mail and numerous other North American media outlets in early May 2023, a proposed update to the guidelines of the USPSTF, the U.S. Preventive Services Task Force, would recommend that women at average risk for breast cancer receive screening mammograms every two years beginning at age 40.
The news has caused quite a stir because it lowers screening recommendations by 10 years from the previous screening guidelines, which called for breast cancer screening at age 50 only due to increased risks for younger populations and too little benefit.

This is a significant change.

According to USPSTF Past President Dr. Carol Mangione, "things have changed": breast cancer rates in young women have increased, advances in digital mammography have improved their detection accuracy, and better treatments result in improved survival.

At this point, we already note two statements that should raise the question of the relevance of screening:
- If the number of cancers in young women is increasing, isn't it time to investigate the causes and identify the elements that contribute to this "rejuvenation" of breast cancers?
- It is the advancement of treatment improvements that have raised breast cancer survival, and the impact of screening in this improvement of survival is now becoming increasingly doubtful, which is further inflated by the over-diagnosis that screening causes. Why advocate it then?
Explanation here: https://cancer-rose.fr/en/2021/03/26/what-is-survival/

Not surprisingly, "The American Cancer Society (ACS) applauds the return of the USPSTF recommendations to begin screening at age 40" in a press releas e. Companies providing imaging services to women, such as Hologic and iCAD, saw their stock prices skyrocket due to the announcement, as volumes of screening mammograms will significantly increase.

And by the way, why not recommend that women be screened by mammography starting at age 40 AND annually, and even throughout their lives without the recommended stop at age 74, so no upper limit?
This is a step blithely taken by the American Cancer Society "because age should not be a determining factor for stopping screening, but rather general health ..." as stated by Stamatia V. Destounis, MD, chair of the ACR (American College of Radiology) Breast Commission and a member of the North American Society of Radiology Public Information Advisors Network.
(For Ms. Destounis's conflicts of interest with imaging industrialist iCAD, see here: https://www.rsna.org/-/media/Files/RSNA/Annual%20meeting/2022-AMPPC-Planners-Disclosure).

JUSTIFICATION AND CONSEQUENCES OF THIS CHANGE

Judith Garber, a science journalist and policy analyst at the Lown Institute, in one article, and John Horgan, also a science writer, in another article, both try to analyze the reasons given by the American agency, which are essentially twofold:
-increase in breast cancers in younger women, and
-an increase in the most aggressive cancers in black women.

Judith Garber correctly notes that "the change in USPSTF guidelines came as a surprise to many health experts, as there have been no new clinical trials on breast cancer screening that would warrant adjusting the guidelines."

A-screening could shorten more lives than it "saves."

"The task force," Horgan explains, "justifies its decision by citing the recent increase in breast cancer among women in their 40s and the higher-than-average mortality rates among black women.
This makes no sense because mammograms do not help women live longer - according to the task force itself! Mammography has been shown to shorten more lives than it saves," according to this review* cited by Horgan, published in 2021.
In any case, both Garber and Horgan explain that even adjusting the predictive models to account for higher cancer rates in young women, the benefit-risk balance is still not much different from the previous USPSTF findings in 2016, with the harms still outweighing the expected benefit.
* "Examining the trend in all-cause mortality reveals that the trade-off between the harms and benefits of mammography has shifted toward the harms over time."

"Change always happens over time as the evidence evolves," says Ruth Etzioni, a biostatistician working at the Fred Hutchinson Cancer Center in the STAT media.
"At the same time, there has to be a compelling reason, and in the literature here, I don't see a compelling reason yet. When I looked at the 2016 modeling studies, the benefit-risk analysis was very similar."

B-The excess of aggressive cancers in black women

"The USPSTF also wanted to emphasize that black women are diagnosed with breast cancer at a more advanced stage and face a higher breast cancer mortality rate than other racial groups," J.Garber resumes; "therefore, an earlier screening start date for these patients could save lives and reduce racial disparities in breast cancer outcomes. However, although the USPSTF has used new models exploring the benefits and risks of screening for black women, it has refrained from recommending earlier screening for black women in particular."
For Ms. Garber:
-lowering the age will not solve the problem of access to care for certain populations.
- lowering the screening age is not enough to reduce racial disparities. Disparities in breast cancer mortality in the U.S. are often the result of structural, social, and economic disparities, with less opportunity for access to care for black populations.

C-benefit on mortality, but what is the trade-off?

The U.S. agency claims that the benefits of mammography, which ideally detects cancer at an early stage when it is easier to treat, outweigh the harms (i.e., false positives and over-diagnosis). But these alleged benefits of screening, which are highly hypothetical and increasingly questioned, only appear in studies that measure breast cancer mortality, and they do not consider the harms associated with overdiagnosis. They do not consider radiation-induced secondary cancers following radiotherapy (secondary bronchial cancers, leukemia), heart disease, which is significantly increased in cancer survivors, suicides, anxiety-depression syndromes, etc.

"For these reasons," Horgan writes, "researchers are increasingly focusing on 'all-cause mortality,' i.e., death from any cause, as a measure of the effectiveness of screening. Death is a strict criterion, leaving no subjective room for maneuvering. Various studies have shown that mammography does not prolong life when all-cause mortality is measured. For this reason, some experts advocate abandoning mammography screening."

J.Horgan cites Amanda Kowalski, a healthcare economist, who presents this data in "Mammograms and Mortality: How Has the Evidence Evolved?" published in the Journal of Economic Perspectives in 2021.
"Over 20 years, women who were screened died at a significantly higher rate than women in the control group," she says. Kowalski notes that screened women had an elevated risk of dying from lung and esophageal cancer; she cites evidence that radiation therapy for breast cancer increases patients' risk of fatal lung and esophageal cancer."
Here's J.Horgan's caveat: "Mammograms may benefit women with above-average breast cancer risk, such as those whose family members have succumbed to the disease. But Professor Kowalski's findings have a devastating consequence: screening healthy, asymptomatic women ends up killing more women than it saves."
This corroborates M. Baum's findings in a 2013 BMJ publication that the harms of breast cancer screening outweigh its benefits if deaths from treatment are considered.

SCENARIOS

The USPSTF's modeling report for its new recommendations presents many scenarios that estimate the rates at which breast cancer screening would result in certain benefits and harms at different ages of onset, duration, and to varying screening rates.

But in every case, a person with no particular excess risk who gets screened is more likely to be treated for cancer that would never have hurt her than to avoid dying from breast cancer. She is more than twice as likely to die of breast cancer anyway, says J.Garber, than to have aggressive cancer detected and successfully treated. And screened women are far more likely to undergo a biopsy unnecessarily or receive a false-positive result than to avoid dying from breast cancer.

It's all about the trade-offs: increasing screening, starting it earlier, and continuing it later, may prevent deaths, but at the cost of how many false positives, over-diagnosis, and over-treatment, which in turn compromise health and survival?
What are the compromises we accept? Is every individual willing to accept the same trade-off as their neighbor?
A decision made in the interest of population health may not be acceptable to every individual. What price is each woman willing to pay for a death from breast cancer to be prevented, knowing that at the same time, other women (including herself) may experience the detection of cancer that would not have been fatal, exposing her to overtreatment, to possible secondary cancer due to radiation therapy for cancer that could have been ignored?

With the lowering of the screening start age from 50 to 40, the USPSTF is effectively saying that to avoid one additional breast cancer death per 1,000 women screened, women must accept an additional 519 false positives, 62 more unnecessary biopsies and two additional cases of overdiagnosis" compared to the false positives, unnecessary biopsies, and overdiagnoses that already exist for screening starting at age 50.

This is exactly what lowering the screening start age by a decade means.

CONCLUSION, a step backward

According to Horgan, these changes in the USPSTF recommendations are not justified. For him, "the lure of profit cannot be dismissed. Breast cancer management is a vast, profitable business, fueled by women's fear of the disease." This cancer business is what he explains at length in this article.

The modeling used to concretely assess what screening will produce "still does not take into account the long-term negative implications of cancer screening (e.g., overdiagnosis) or the fact that tumors sometimes grow in unexpected ways, or the fact that tumors sometimes grow and regress at different rates," as V. Prasad, an American professor of oncology and hematology, explains in his 2021 video.

Other reactions note the very lucrative nature of this new recommendation: https://radiologybusiness.com/topics/medical-imaging/womens-imaging/uspstf-recommends-women-begin-breast-cancer-screening-40-boosting-stocks-mammo-related-firms
The Radiology business says, "The U.S. Preventive Services Task Force released new recommendations on breast cancer screening Tuesday, now urging all women to be screened every two years starting at age 40.
The draft guidelines mark a change from previous USPSTF standards, which called for screening starting at age 50. Women's imaging vendors such as Hologic and iCAD saw their stock prices soar Tuesday morning following the news, as screening volumes are expected to increase.
The influential USPSTF had previously encouraged women to "make an individual decision" about when to begin screening before age 50, but is now reversing course and aligning with guidelines set forth by medical societies."

This move, which you can bet will be adopted in other Western countries, can be viewed as a real step backward at a time when modern medicine is more about measured, weighted thought in collaboration with the patient, and when the question of de-escalation of harmful routine procedures was beginning to be asked.

Without any evidence, women's information is being put at risk once more, with the message that more screening equals saving lives.

At the same time, the Council of Europe calls for caution.
Even the American Cancer Institute encourages guideline developers (study financed by the NCI) to do more research before updating their guidelines for revision to ensure that the best possible data on the adverse effects of screening are used to make their recommendations.

We are a long way from that...

20 March 202320 March 2023

Breast density notifications: implications and overuse

Translation by Cancer Rose, an article published by Judith Garber, a political scientist at the Lown Institute, a nonpartisan think tank for a more just and equitable health care system.

March 18, 2023

LOW-VALUE CARE

New FDA guidance on breast density notifications and the implications of overuse - BY Judith Garber | March 10, 2023

Background

The radiological criterion of "breast density," the predominance of fibroglandular tissue over fatty tissue in the female breast, is now considered to be a risk factor for breast cancer on its own, despite the lack of evidence-based studies.

Breast density is generally high in young, non-menopausal women (but may persist after menopause), in thinner women with low body fat, and in women undergoing menopausal hormone replacement therapy.

A law passed in 2019 by the U.S. Congress required the U.S. Food and Drug Administration (FDA), as part of the regulatory process, to ensure that all mammography reports and summaries provided to patients include information on women's breast density. This authority, which oversees the regulation of mammography facilities and quality standards, has previously required the reporting of breast density in radiologists' reports.

It's done. The FDA recently updated its guidelines to require mammography facilities to inform patients of their breast density.

Why is this an emerging concern for European women populations as well?

Because with the advent of so-called predictive software, the radiological criterion of breast density is being incorporated as a risk factor in its own right in studies such as the European MyPEBS for individualized screening, whereas published studies (see article) show that the increase in breast cancer risk associated with breast density is modest and that for women diagnosed with breast cancer, increased breast density was not associated with an increased risk of poor prognosis cancer or death from breast cancer.

The FDA's decision is supposed, according to Volpara, a company that markets automatic breast density measurement software, to serve as an example "to the rest of the world." (See the very last chapter of this article, "Cancer Rose comments")

The USPSTF (independent task force reviewing U.S. preventive services), already in 2016, raised several points of concern about this legislation requiring women to be notified of their breast density information.
- Significant variability and limited reproducibility in the determination of dense breasts. This variability exists whether one radiologist or different radiologists read it. The exam for a given patient may have different classifications and lead to misunderstandings leading to a reduction in a woman's confidence in screening in general and confusion about her breast cancer risk.
- Uncertainty about steps taken by women notified of significant breast density to reduce their risk of dying from breast cancer. This is the request for additional tests for which no evidence supports the indication. There is no evidence that adding imaging other than mammography for women with dense breasts will reduce cancer mortality; these additions increase false positives, unnecessary biopsies, and overdiagnosis. The recall rate (for false positives) is significantly increased by the addition of ultrasound (by 14%) and by the addition of MRI (from 9 to 23%) with low PPVs[16] and an obvious additional cost. The authors remind us that MRI, often considered harmless, would be susceptible to a (low) excess risk of nephrogenic systemic fibrosis and uncertain risks of gadolinium deposition in the brain when the examinations are repeated.
Tomosynthesis (TS) is mentioned as an additional technique used. Still, the authors point out that longer-term studies are needed to determine whether the routine use of TS in women with dense breasts improves breast cancer outcomes (mortality, decrease in the rate of serious cancers).
- Difficulty communicating information about breast density to patients. Experts consider this communication complex and dependent on the population's literacy level. Study results show poor understanding, confusion, and misinformation among patients when information about breast density is given.

Article of Judith Garber

-Follow link for the complete article-

The US Food and Drug Administration (FDA) recently updated their mammography guidelines to require mammography facilities to notify patients about their breast density. This change, which goes into effect September 2024, is a final version of a rule proposed in 2019 (see our previous coverage on this topic).

The FDA guidelines contain suggested language for notifications about breast density:
“Breast tissue can be either dense or not dense. Dense tissue makes it harder to find breast cancer on a mammogram and also raises the risk of developing breast cancer. Your breast
tissue is dense. In some people with dense tissue, other imaging tests in addition to a mammogram may help find cancers. Talk to your healthcare provider about breast density, risks for breast cancer, and your individual situation.”
There are a lot of issues here.....

Comments Cancer Rose

Conflicts of interest of Dense Breast Info members can be seen here in the list by following this link: https://www.rsna.org/-/media/Files/RSNA/Annual%20meeting/2022-AMPPC-Planners-Disclosure

RSNA: Radiological Society of North America, it is a non-profit organization and an international society of radiologists, medical physicists and other medical imaging professionals

Among the "educational supports" we find the Volpara Society. Volpara is a publicly traded New Zealand company (Volpara Solutions Ltd.) that markets software to generate standardized breast density measurements automatically.

Volpara's Investor Statement on 30 Sep 2022 reads:
https://wcsecure.weblink.com.au/pdf/VHT/02601721.pdf

“Volpara is delivering strong growth in line with its upgraded guidance of between NZ$33.5M and NZ$34.5M. We continue our strategy of balancing purpose with profitable growth leveraging focus: our most profitable products, most lucrative markets, and providing the best value for "elephants," or large enterprise accounts. We await the release of the FDA’s breast density legislation, expected between now and early 2023, as per the latest FDA release, which can be found here. “

"Waiting for the Mandate on Breast Density by FDA

- late 2022/early 2023

- Validates the importance of breast density

- Set an example for the rest of the world

- Federal decision = everyone should be informed

- Breast density is considered in risk assessment"

For example, a radiologist extremely well known in the Canadian media, Dr Paula Gordon, who advocates for early breast cancer screening and challenges the CanTaskForce** recommendations for caution, is a shareholder of Volpara company. We can thus read her regular statements in the Canadian press, describing the

Canadian group CanTaskForce as "killers of women":

1- https://theprovince.com/opinion/op-ed/dr-paula-gordon-new-breast-cancer-screening-guidelines-are-going-to-kill-many-women
"Dr Paula Gordon: New breast cancer screening guidelines will kill many women"

2-https://medicinematters.ca/breast-cancer-screening-mammogram-policies-are-based-on-flawed-research-dr-paula-gordon/
"Policies on breast cancer screening mammograms are based on flawed research / Dr Paula Gordon

3-https://globalnews.ca/news/8239335/breast-cancer-screening-canada-report/
"Outdated" breast cancer screening guidelines are failing Canadian women."

** The Canadian Task Force on Preventive Health Care was established by the Public Health Agency of Canada (PHAC) to develop clinical practice guidelines that support primary care providers in delivering preventive health care.

25 February 202326 February 2023

Interval cancers, incidentalomas, the losers of screening

Cancer Rose summary, February 20, 2023

A-the interval cancers

https://www.academicradiology.org/article/S1076-6332(23)00020-X/fulltext

A retrospective cohort study* published in February 2023 in "Academic Radiology" compares the characteristics of interval breast cancers, the so-called false negatives, i.e., cancers that were not detected at mammography and occur between two screening mammograms, with breast cancers detected at screening mammography.

What is interval cancer, why is it very frustrating for women participating in screening, and what are the study's findings on their characteristics?

* A type of investigation that consists of examining, based on data present in medical files or in data registers, a defined population (the cohort) and comparing a criterion or an event (here the characteristics of breast cancer) observed with one or several other groups of individuals defined according to criteria (age, living conditions, etc.)

illustration from C. Bour's book "mammo ou pas mammo?" Souccar edition

There can be two different scenarios:

1° cancer already exists and is really "missed"-

The mammographic examination is not infallible. Dense breasts are difficult to explore, and the glandular tissue is very present, resulting in a kind of opacity on mammography that prevents cancer detection. Some cancers are said to be "infiltrating" and blend in with the breast tissue. Others are atypical in shape, and still, others are completely hidden: they are not visible; the woman feels a lump one day, but the cancer is still not identifiable on mammography.

2° interval cancer

Interval cancer is cancer that was not present at the time of the mammographic examination or was only present in the form of cells. But its aggressiveness and growth are such that it develops very quickly, in a few days, weeks or months, thus in the theoretical interval between two screening mammograms, hence its name.

This situation is very frustrating for the patient, who has been told that screening is protective and saving and feels that she has "done everything right" but is not well rewarded for her diligence.

A false negative !

"Meh, small benign warts!" illustration from the book by C.Bour "Mammo ou pas mammo ?", edition T.Souccar

Results of the study

The major conclusions drawn by the authors are that interval cancers, in comparison with those detected by mammography, are, on average :

- More frequent in women with dense breasts (almost three times more)
For the authors, breast density remained significantly associated with the development of interval cancer.
When stratified by age, breast density was only significant for women over 50. This may be because dense breast tissue is more common in younger women, being present in more than 50% of women under 50 but only in less than 30% of women over 70.

- It is more advanced and has worse biological characteristics than cancers detected by mammography. In other words, screening detects mostly low-stage cancers and carcinomas in situ, many of which contribute to the pool of overdiagnosis.
Compared with screen-detected cancers, interval cancers were more often invasive than ductal carcinoma in situ (88% versus 75%, p = 0.007).
In addition, 43% (41/96) of interval cancers were primary tumours of stage 2 or higher, compared with only 12% (139/1136) of screen-detected breast cancers (p < 0.001).
Interval cancers were most often diagnosed because of symptoms and abnormalities in the breast.

- Women with a family history of breast cancer, especially first-degree (mother, sister, daughter), compared with women diagnosed with screen-detected cancer. However, family history was insignificant in multivariate analysis (a statistical method used when multiple factors potentially influence an outcome).

Conclusion of the authors

The aggressive phenotype of interval cancers may explain why they were not visible at the initial screening examination but were detectable less than a year later. These cancers are likely to be fast-growing, either new or too small to be visible at screening. The authors note that this was explicitly studied by Gilliland et al.

Furthermore, in subset analysis, interval cancers diagnosed at high-risk screening MRI were more likely to be ductal carcinoma in situ and stage 0 or 1 primary tumours, compared with symptomatic interval cancers...

For the authors, this would confirm the usefulness of screening MRI for high-risk women with high breast density, as MRI helped identify some interval cancers at an earlier stage than interval cancers identified by patients due to a symptom in the breast.

(However, it may be objected that the discovery of an earlier stage cancer in high-risk women does not tell us whether it is an interval cancer that was actually detected earlier and will thus be prevented from progressing or whether it is an intrinsically favourable cancer that would not have progressed or would have progressed little. To learn more about the problem of additional MRIs (overdiagnosis, cascades of examinations, false positives), read : https://cancer-rose.fr/en/2021/01/26/additional-mri-screening-for-women-with-extremely-dense-breast-tissue/

Cancer Rose Commentary

We repost the commentary from the excellent blog of our fellow Dr Agibus -

In his Dragiwebdo post #386, chapter 5, Dr Agibus summarizes the study's conclusion very well by recalling the so-called "barnyard" pattern, barnyard analogy breast cancer screening -

Below is what he writes:

"One paper explores mammography and interval cancers. The authors compared cancers diagnosed on screening mammograms with those diagnosed while a previous screening mammogram had been performed. They found that interval cancers were of higher stage and poorer prognosis (triple negative, adenopathy) than cancers discovered during screening. This study confirms (or at least appears to support) that screening mammography detects cancers that are not very aggressive (rabbits and turtles, sometimes too turtles, in fact). In contrast, aggressive cancers (birds) slip through the cracks and are detected on symptoms, even in the case of regular mammograms. For reminder :

In other words, aggressive cancers are intrinsically aggressive, so they are not anticipated. Those detected by repeated mammography correspond to less severe and curable cancers, with a sufficiently long residence time in the breast so that screening can detect them, but of which a large part contributes to over-diagnosis (especially the carcinoma in situ). For explanation, read: https://cancer-rose.fr/en/2020/12/17/are-small-breast-cancers-good-because-they-are-small-or-small-because-they-are-good/

B-the incidentalomas

https://www.birpublications.org/doi/10.1259/bjr.20211352

Here the authors warn of unnecessary findings in routine examinations, leading to so-called "cascades of examinations".

One of the paradoxes of modern medical imaging, they say, is that the source of our greatest achievement - the ability to image the human body in ever greater detail - is also the source of one of our most significant challenges.

The success of medical imaging as a diagnostic tool has led to a dramatic increase in its use. Technological advances make it possible to acquire images at higher resolution and in more significant numbers than ever before. This has led to an increase in the detection of findings that do not appear to be related to the primary purpose of the examination and have been referred to as "incidental," This is especially true of CT and MRI scans. Many of these are harmless, but some have significant consequences for the patient's health.

Radiologists, authors say, need to become familiar with the most common incidental findings to assess their significance in each case best and to be able to recommend appropriate further investigations, when justified, because these incidental findings have implications for the patient and the service as a whole and must be thought through carefully.

Incidental findings are defined as all findings that are not directly related to the main purpose for which the imaging examination was performed, for example, the discovery of an adrenal nodule without any complaint from the patient during a CT scan or ultrasound for abdominal pain, a common and not always very specific symptom. Or the discovery of a renal nodule during a CT scan for pulmonary disease.

The development and potential widespread introduction into clinical practice of blood tests for circulating tumour DNA may add another layer of complexity.
Read here : https://cancer-rose.fr/en/2022/09/16/liquid-biopsies-the-grail/

This increased rate of detection brings with it a number of problems. The authors explain:

“Sometimes the images themselves may include features which allow us to be reasonably confident that a particular finding is either important or not - site, size, morphology, attenuation or signal characteristics may all be helpful. In many other cases there will be doubt and a decision must be made about how best to manage this uncertainty.

If it is decided that a particular lesion cannot be dismissed as irrelevant, further imaging or other more invasive tests may be recommended. The impact on the patient can range from anxiety and minor inconvenience to real harm in the event of a complication from an invasive procedure such as biopsy or endoscopy.

Much has been written about the concept of overdiagnosis – the detection and subsequent treatment of disease which if left alone would not cause problems in the patient’s lifetime. Although the term is most commonly used in relation to screening programmes, it applies equally to IFs found in symptomatic patients.”

The person lives with and will die with their cancer, not because of it.
*Illustration from C.Bour's book "mammo ou pas mammo?", T.Souccar edition*

The story of early diagnosis is seductive, but the term cancer - as it is currently used - covers many different diseases, including some indolent lesions that traditional therapeutic strategies would overtreat. (Editor's note: one reference cited is for low-grade DCIS). It is hoped that developments in artificial intelligence will help us in the future to better stratify these patients into different management strategies, some of which may involve observation rather than intervention.

For now, there is still a significant risk that the detection and reporting of an IF will result in over treatment. Aside from the impact on the individual patient, there are significant implications for radiology services, particularly in a constrained tax-funded system...
The direct cost of follow-up investigations is one consideration but an even greater risk is the potential that an increase in the number of studies performed to follow-up incidental findings will inevitably make services harder to access for other patients, some of whom may have greater need."

The conclusion:

" Firstly we must accept that given the uncertainties inherent in radiology practice and the limitations of the tests we use, we will not always get it right.
Next we should put ourselves in a position to make the best possible assessment as to the likely relevance of each finding. We should acquaint ourselves with the appearances of the common IF in each organ as described in the articles which follow, together with the features which in each case give the best possible steer as to their likely importance.
Finally we must recognise that choosing to mention any particular finding in a radiology report is not a neutral act – it carries consequences for the patient, for the service and for other patients. For the patient, we are potentially committing them to further tests, some of which may cause concern or even real harm. For the service we are imposing a burden…”

Our conclusion

We all have a duty and responsibility to make medical decisions about the examinations we order and perform for the patient's benefit. Not only prescribers but also radiologists must ask themselves about the scope of what they are looking for and then, for radiologists, what they are describing. How much weight and importance should be given to what they find?
Simply listing images and leaving it up to the treating physician to decide what to do with them puts the responsibility for the outcome on the prescriber alone.

Patients, too, need to be adequately informed of what systematic, routine examinations, or examinations, as we sometimes read on prescriptions, of "reassurance" may involve for their health.

Screening examinations are not infallible or harmless. They are not unstoppable shields against diseases. They can "miss" genuine lesions. They can make the patient discover unnecessary things and fall into a disease they would never have known without them.

Incidental Findings and Low-Value Care

Invited Clinical Perspective Matthew S Davenport MD-2023 Jan 11.
Departments of Radiology and Urology, Michigan Medicine, Ann Arbor MI 48108
doi: 10.2214/AJR.22.28926. Epub ahead of print. PMID: 36629303.

https://www.ajronline.org/doi/abs/10.2214/AJR.22.28926

Highlight:

Detection of incidental findings in a low-risk population generally results in low-value and potentially harmful care, including paradoxically for many cancers

Summary

Incidental findings are analogous to the results of screening tests when screening is applied to unselected, low-risk patients. They generally result in low-value and potentially harmful care. Patients with incidental findings but low risk for disease are likely to experience length bias, lead-time bias, overdiagnosis, and overtreatment that create an illusion of benefit while conferring harm. This includes incidental detection of many types of cancers that, although malignant, would have been unlikely to affect a patient’s health had the cancer not been detected. Detection of some incidental findings can create high-value care, but most do not, and differentiation is often unclear at the time of identification. Higher patient- and disease-related risk increase the likelihood an incidental finding is important. Clinical guidelines for incidental findings should more deeply integrate patient risk factors and disease aggressiveness to inform management. However, lack of outcome and cost-effectiveness data lead to reflexive management strategies that create low-value, expensive, potentially harmful care.
Radiology needs outcome and cost-effectiveness data to inform its management recommendations for incidental findings.

So, What Should We Do?

It is increasingly recognized that incidental findings are incompletely understood, expensive, and surprisingly harmful. Rather than a benefit of imaging, they are usually a harm. They are not sought, the odds of them being important is low, and they create tremendous uncertainty and low-value care. The pragmatic challenge is what to do about it in the near- and medium-term.
Some have wondered if certain incidental findings should not be reported at all. The medicolegal environment complicates matters. Some incidental findings are cancer. Sophisticated understanding of the biases which predict low-value care—that early detection of some cancers can produce a paradoxically worse outcome than had those cancers never been detected at all—is not a reasonable thing to expect of patients or the legal system in 2022; it is difficult for medical practitioners to understand. But we shouldn’t simply maintain the status quo. Here are several recommendations.

First, we should heed the call to action raised by some asking us to be more aware of the harms of overdiagnosis and overtreatment cascading from the detection of incidental findings. Incidental findings are a complication of diagnostic imaging—inadvertent harm despite positive intent—like bleeding following an image-guided biopsy. The specific harms of incidental finding management are opaquer than bleeding and harder to understand. But this simply means we (radiologists) should take a more active role in studying and managing them. It is our complication and our challenge to solve.

Second, we should advocate for incidental findings guidelines, especially our own but others as well, to explicitly incorporate and recommend appropriate studies to confirm they are working as intended. Working as intended means “producing high-value care”.
We should expect incidental findings guidelines to emphasize the creation of high-value care rather than an exclusive or overweighted focus on maximizing diagnostic sensitivity. This is not a radiology-only dilemma. Incidental findings guidelines exist in many medical and surgical specialties, and we should work collaboratively with them to promote a high-value approach.

Third, we should advocate for funding organizations to prioritize the study of incidental finding management. We have a compelling argument. Incidental findings are ubiquitous and an enormous burden on the health care system. Randomized trials could be conducted in which deferral of aggressive diagnosis and management is a treatment arm. The emergence of active surveillance as a valid strategy for many cancer types is a precedent we can follow, apply, and expand upon here.

Fourth, we should avoid being alarmist in our reporting. Yes, at present, we should follow the guidelines we support until stronger evidence arises, but we also should recognize that most incidental findings are not harmful if left alone in low-risk patients. Low prevalence of disease and the biases inherent to screening help explain why this is so. When in doubt about the significance of an incidental finding, and the guidelines are unclear or give leeway, err on the side of minimizing it.

Fifth, because the clinical importance of an incidental finding is highly dependent on patient risk, we should pursue information technology solutions, in collaboration with referring providers, to make relevant risk factors more visible to radiologists (e.g., hypertension uncontrolled on multiple medications [adrenal nodule], unreported head and neck cancer [liver lesion]). In current state, radiologists often rely on a brief historical snippet focused on the chief concern to interpret an examination. Incidental findings are definitionally unrelated to the chief concern and therefore not always informed by it.

Sixth, in our reporting, we should attempt to balance diagnostic sensitivity with other competing risks.
We should understand the cascading harm that can result from management of an incidental finding and allow that potential for harm to influence our recommendations. We are still largely ignorant about which incidental findings are important and how best to manage (or ignore) them. In the years between now and a clear solution, we should do our best to minimize collateral harm to the patients we are trying to help.

29 December 202229 December 2022

A letter from Ameli (French Health Insurance)

27 October 2022, by Cancer Rose
Updated December 2022

Dear Sir or Madam,

Your attending physician plays a central role in prevention actions. Depending on your situation, he can inform you and answer your questions about organized screening for breast, cervical and colorectal cancer, which can save lives. The earlier these cancers are detected, the better the prognosis.
To help your doctor in his mission of providing health advice to his patients, the Health Insurance will provide him with the list of his patients concerned by these screenings and who have not completed them (1).
Under the provisions relating to personal data protection, you have until December 1, inclusive, to oppose this transmission via the following link: https://www.demarches-simplifiees.fr/commencer/declarer-mon-opposition.
If you make your objection after December 1st, your request will not be considered for the first available list but will be considered for future lists.
Your situation could mean that some of these organized screenings do not apply to you; in this case, please disregard this message.

Please be assured of our attention and availability,
Your Health Insurance Correspondent

This is the letter that everyone has received from their Health Insurance.

Remember that during the citizens' consultation, the Health Insurance Institution's simplistic communication was criticized; read pages 95 and 96 of the citizen consultation on breast cancer screening report.
It cannot be stated that communication is more advanced in 2022, leaving any opportunity for reflection or doubt.

In this email, it is claimed that these screenings save lives. However, there is no scientific evidence, no study given, no justification, and no single reference. The message notifies you that your attending physician will be informed of the screenings you have not yet completed...
Ideally, one would hope that this approach would encourage discussion with the family physician about the relevance of screening, leading to a consultation that would result in a shared decision and information that would allow an informed choice. But what about in real life? One of our readers correctly asks if this will not instead allow putting a little more pressure on patients to participate in screenings that are losing momentum rather than an informed decision consultation if the health insurance institution itself starts with the presumption that screenings save lives, which is far from reality. There is little communication about the scientific challenges still rising regarding the true relevance of screening and its harms. [1] [2] [3] [4] [5].

The user who receives this email must activate the rejection; hence, if he does not click on the link allowing him to oppose, his acceptance is activated by default.

This initiative appears to be a part of the larger European plan to increase European population participation in various screenings, despite many scientists' requests for better information on the benefit-risk balance of these health programmes.
The target is for 90% of EU citizens to participate in colorectal, breast, prostate, and cervical cancer screenings by 2025.

The new French 10-year plan states (https://www.e-cancer.fr/Institut-national-du-cancer/Strategie-de-lutte-contre-les-cancers-en-France/La-strategie-decennale-de-lutte-contre-les-cancers-2021-2030):

“Improving access to screening will be strengthened.”

"It will be a matter of better understanding the determinants of reluctance to screening and simplifying access to screening (direct order, diversified health professionals, mobile teams in particular). Approaches will be developed that offer screening after a preventive intervention or unscheduled care.

For example, partnerships with food aid organizations will be considered to carry out awareness-raising efforts, particularly among the most disadvantaged. First, contact information tools for health, medical, and social workers will be provided, and mobile applications with information and reminders will be developed. To encourage people to participate in screening, material incentives will be tested. Finally, screening age limits will be reconsidered. "

The financial incentives specified in the text allow for the recruitment of the most economically disadvantaged people, again disregarding any medical knowledge, as was denounced in an article in the BMJ, whose one of its authors is a French citizen[6]. For these more vulnerable persons, the consequences of abusive screening can be dramatic, resulting in impoverishment, loss of income, and difficulty getting jobs.
The problem of these underprivileged people is much more the access to care than finding unnecessary cancers that would never have harmed them. It is also a problem of good medical information and fight against risk factors to which they are more exposed.

But sometimes, too much is the enemy of the good. With the other screenings of the European plan that are going to be added with new invitations, reminder letters, mobile applications, and increased medical consultations, the effect obtained could be the opposite: a weariness of the population, already more and more distrustful of medical injunctions, and who will turn away, as it is already the case, from traditional medicine that is more and more coercive and harassing.

Enough is enough.

Update December 2022

https://www.ameli.fr/medecin/actualites/depistages-organises-des-cancers-envoi-aux-medecins-traitants-de-listes-de-patients-eligibles

The summum is reached in a communication dated November 23, 2022, in which doctors are explicitly asked to incite their patients to undergo screening.

In addition to the ROSP system (remuneration based on public health objectives, which is already highly questionable and contested), the Assurance Maladie (French National Insurance) wishes to strengthen the role of primary care physicians in inciting screening by using lists of patients who are eligible but have not participated in screening.

"The effectiveness of these screenings has been demonstrated because the earlier cancers are detected, the better the prognosis: they save lives," they write in their letter.

This is inaccurate, incomplete, and unethical in its deliberate silencing of the harms and risks of screenings, for which the citizen consultation requested clear information for women. The EU Council has recently reaffirmed and reiterated this demand for transparent information.

The Health Insurance views the doctor as a simple inciting player for patients who are listed and are not compliant with the screening; the comprehensible information requested by the citizens, which is the primary responsibility of the attending physician, is thus buried, and informed consent is a utopia....

Communication text :

Organized cancer screenings: lists of eligible patients sent to attending physicians

November 23, 2022

At the beginning of December, the Assurance Maladie (French National Health Insurance) will mail to attending physicians a list of their patients who have not had cancer screening (cervical cancer, breast cancer, and colorectal cancer) within the recommended intervals.

Based on the double observation that France lags behind its European neighbors in terms of participation rates in organized screenings and that these have stagnated since 2018, Assurance Maladie wishes to strengthen the role of attending physicians in inciting screenings by providing them with a list of their eligible patients.

These screenings have demonstrated effectiveness because the earlier cancers are detected, the better the prognosis: they save lives.

The crucial role of general practitioners in screening participation has been demonstrated both in France and abroad. Because of their privileged relationship with their patients, doctors can incite them to undergo these screenings and answer their questions during a consultation.

To facilitate the execution of this public health mission, the list made available to attending physicians includes their patients who have not participated in the screenings for which they are eligible, according to the recommended intervals, whether within the framework of organized screenings or an individual approach.

These are:

- women aged 25 to 65 for organized cervical cancer screening ;
- women aged 50 to 74 for organized breast cancer screening;
- women and men aged 50 to 74 for organized colorectal cancer screening.

Please note: despite all the attention paid by Assurance Maladie to the targeting of the insured persons on this list, it is possible that some of them are not concerned (specific follow-up, recent screening, etc.). Some patients may have expressed opposition to being included on these lists.

References

[1] https://cancer-rose.fr/en/2022/09/13/the-risks-of-screening-an-elephant-in-the-room/

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

[3] https://www.nejm.org/doi/full/10.1056/NEJMoa2208375

[4] https://cancer-rose.fr/en/2021/02/01/overdiagnosis-of-thyroid-cancer-another-womans-concern/

[5] https://cancer-rose.fr/en/2021/02/24/being-a-woman-and-smoking-x-rays-in-perspective/

[6] https://www.bmj.com/content/376/bmj-2021-065726

20 December 20221 January 2023

Screening: it is urgent to improve the information for women

DECEMBER 14, 2022, BY CANCER ROSE

Recently, we relayed the EU Council's new screening guidelines, which we found to be rather prudent and thoughtful.
The text of the EU Council can be found here.

In broad terms, the Council emphasizes the need for additional information on the effectiveness, cost-effectiveness, and feasibility of certain screening strategies in the real life, especially for new screenings such as prostate, lung, and stomach cancer.
Member States are invited to evaluate the introduction of cancer screenings based on conclusive scientific evidence, taking into account the balance between the benefits and risks of the screenings, about which the public should be informed.

Publication in the Official Journal

The text has been published in the Official Journal. The following paragraphs seem to be of capital importance because they reflect the 2016 French citizens' consultation demands.

(8) “Screening is the process of testing for diseases in people in whom no symptoms have been detected. In addition to its beneficial effect on disease-specific mortality and on incidence of invasive cancers, the screening process also has inherent limitations, which can have negative effects for the screened population. These include false positive results, which can cause anxiety and may require additional testing that may pose potential risks, false negative results, which provide false reassurance leading to delays in diagnosis, overdiagnosis (i.e. detection of cancer not expected to cause symptoms during the patient’s lifetime) and subsequent overtreatment. Healthcare providers should be aware of all the potential benefits and risks of screening for a given type of cancer before embarking on new organised cancer screening programmes. Furthermore, these benefits and risks need to be presented in an understandable way that allows individual citizens to give informed consent to participate in the screening programmes.”

(24) It is an ethical, legal and social prerequisite that cancer screening should only be offered to fully informed people with no symptoms, if the benefits and risks of participating in the screening programme are well-known and the benefits outweigh the risks, and if the cost-effectiveness of the screening is acceptable. This assessment should be an inherent part of the implementation at national level.

The Council also recommends, in the same text, that Member States :

(4) “ensure that benefits and risks, including potential overdiagnosis and overtreatment, are presented to the people participating in the screening in an understandable way, potentially including on a health professional-to-participant basis, allowing individuals to express informed consent when deciding to participate in the screening programmes, and that the principles of health literacy and informed decision-making to increase participation and equity are taken into account;.”

Improving women's access to information: an absolute necessity

We emphasized the insufficient information in the INCa booklet sent to women, which, although some changes over the previous one, still lacks a visual pictogram allowing a simple understanding of the benefit/risk balance and does not mention screening risks but instead uses the term "limits" along with explanations to minimize them.

Download / Télécharger

This publication is not in accordance with EU Council recommendations.
It is sent to the woman only once when she reaches the age of 50, after which she will only receive a leaflet at each subsequent screening, that fails to mention any of the risks of screening and refers to a website that is similarly susceptible to criticism. Over the course of a woman's lifetime, it is evident that the message that will remain in her memory will be the "embellished" leaflet, that omits the risks completely.

LeafletJune21 Télécharger

Leaflet - Breast Cancer Screening. Practical guide

This leaflet, whose content is largely based on that of the booklet, will be sent to women aged 50 and over when they renew their invitation to participate in the DOCS. It can also be distributed at information meetings.

In the EU Council's document, the different risks of screening, such as false alarms and overdiagnosis, are well defined (in part 8). In contrast, in the INCa leaflet, the definitions of these concepts are sometimes imprecise, often minimized, the definition of overdiagnosis is incomplete, and overtreatment is not explained (see our analysis).
In the booklet, there is no mention at all of overdiagnosis.
It is therefore urgent, based on the EU requirement regarding the presentation of screening risks to targeted populations, to improve the information provided to women invited to screening beyond the age of 50, from the age of 52 onwards, while also respecting the requirements for good literacy and without obscuring the concepts of false alarm and overdiagnosis, the two major risks of breast cancer screening.
In addition, 5-year survival is highlighted as a "benefit" in both the booklet and the leaflet, despite the fact that it is not a measure of screening effectiveness.
In the recommendation of the Council, it is stated:
(6) The main indicator of the effectiveness of screening is a reduction in disease-specific mortality or in incidence of invasive cancers.

In addition, the presentation of benefits and risks does not conform to EU Council recommendations for comprehension. The reduction in breast cancer mortality is given as a relative percentage reduction (15-21%), whereas the percentage of overdiagnosis is described as an absolute percentage (10-20%), making comparison impossible. This flaw already exists in the 2017 publication.
A 20% reduction in cancer mortality does not correspond to 20 fewer cancer deaths per 100 women screened.

This is an indication a relative risk only. 20% fewer deaths does not imply that 20 fewer women out of 100 will die of breast cancer if screened. The 20% reduction in mortality is simply a relative risk reduction between the two groups of women being studied.
In fact, according to a projection produced by the Cochrane Collective based on numerous studies, out of 2,000 women screened over a 10-year period, four die of breast cancer, whereas out of the same number of women who were not screened, five die of breast cancer. The shift from five to four represents a 20% reduction in mortality, but in absolute terms, just one woman's death will be prevented (absolute risk of 0.1% or 0.05%).
The range of 10-20% provided for the rate of overdiagnosis represents the lowest estimate. Other research indicate substantially higher overdiagnosis rates. Overdiagnosis is largely overlooked in the leaflet, and there is a striking omission of risk information that is easily understood.

Read more:

What could be improved?

It is time for the health authorities to finally respond rigorously to the Council's recommendations published in the Official Journal and to respect the French population by complying with these recommendations.
These recommendations state that "the benefits and risks must be presented in an understandable way to allow citizens to give their informed consent to participate in screening programs."

To do this, a modern and validated strategy employs decision support tools, such as the one developed by the Harding Center for Literacy, which describes how harms might be presented visually.
https://www.hardingcenter.de/en/transfer-and-impact/fact-boxes/early-detection-of-cancer/early-detection-of-breast-cancer-by-mammography-screening

The methodology is perfectly described here:
https://www.hardingcenter.de/de/transfer-und-nutzen/faktenboxen,
with the reference: https://www.hardingcenter.de/sites/default/files/2021-06/Methods_paper_Harding_Center_EN_20210616_final.pdf
8) Page 13, “Handling numbers and presentation of risks. The benefits and harms of medical intervention are balanced in fact boxes. By specifying the references and using the past tense, it is clear that these are study results, and thus no individual prediction is possible. The reference in numbers is always the same for the intervention and control groups. The event frequencies are communicated in absolute numbers. Relative risks are not reported. Which reference value is chosen (100, 1,000, or even 10,000) depends on the study data. It has to be ensured that the indication of integers is possible and that existing statistically significant differences become clear. The absolute change in risk is shown in the short summary of the fact box and the accompanying text. Mismatched framing (the presentation of advantages and disadvantages in different formats) is not used. ”

Another illustration is available in the WHO guide, on pages 37/38
https://apps.who.int/iris/handle/10665/330829
“Both laypeople and clinicians tend to overestimate the benefits of screening and underestimate the harm of screening (36). Training personnel on communicating risk and tools such as infographics, videos and decision aids can be used to facilitate understanding and promote informed consent and evidence-informed practice (Fig. 15).”
See the infographic on page 38
We propose on our side a short illustrated tool, "Cancer Rose", based on French data, which you can consult here: https://cancer-rose.fr/en/breast-cancer-decision-aid/

To conclude

The Council of the EU has issued recommendations, particularly on public information and the presentation of information that meets citizens' demands.

- The WHO calls for the respect of the Wilson and Junger principles (read here, middle of the article);

- the French citizen and scientific consultation asks for an improvement of the information with an honest and neutral presentation of the data,

- the EU Council strongly recommends an understandable presentation of the risks of screening, so what is the additional step that our French health authorities need to take in order to honestly and sincerely explain the benefits and risks to women allowing them to make a real informed choice?

We must stop hiding the risks of screening, to which women are shamefully subjected. Instead, we should inform them that screening might expose them to inconveniences and risks, including overdiagnosis, which can unnecessarily lead to a disease they would never have known without it.

Yes, it's really time....