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

1.

Vanchieri  C.  National Cancer Act: a look back and forward.   J Natl Cancer Inst. 2007;99(5):342-345. doi:10.1093/jnci/djk119PubMedGoogle ScholarCrossref

2.

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

3.

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/NEJMp1209407PubMedGoogle ScholarCrossref

4.

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

5.

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
ArticlePubMedGoogle ScholarCrossref

6.

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
ArticlePubMedGoogle ScholarCrossref

7.

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/cam4.2476PubMedGoogle ScholarCrossref

8.

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

9.

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/NEJMoa2208375PubMedGoogle ScholarCrossref

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)30396-3PubMedGoogle ScholarCrossref

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)30358-3PubMedGoogle ScholarCrossref

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/djr284PubMedGoogle ScholarCrossref

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/M17-1441PubMedGoogle ScholarCrossref

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/M22-0835PubMedGoogle ScholarCrossref

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/91.5.434PubMedGoogle ScholarCrossref

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-2011-300774PubMedGoogle ScholarCrossref

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.50.1.29PubMedGoogle ScholarCrossref

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.6136PubMedGoogle ScholarCrossref

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
ArticlePubMedGoogle ScholarCrossref

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)60525-0PubMedGoogle ScholarCrossref

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.2018.01.080PubMedGoogle ScholarCrossref

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/djr500PubMedGoogle ScholarCrossref

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/NEJMoa1911793PubMedGoogle ScholarCrossref

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.201505-1040OCPubMedGoogle ScholarCrossref

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-2016-209825PubMedGoogle ScholarCrossref

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.g366PubMedGoogle ScholarCrossref

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.43.2.107PubMedGoogle ScholarCrossref

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:10.1177/0969141319839097PubMedGoogle ScholarCrossref

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.32539PubMedGoogle ScholarCrossref

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.l5515PubMedGoogle ScholarCrossref

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-2019-032773PubMedGoogle ScholarCrossref

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.k3519PubMedGoogle ScholarCrossref

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/M19-2125PubMedGoogle ScholarCrossref

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.2019.05.044PubMedGoogle ScholarCrossref

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/dyu140PubMedGoogle ScholarCrossref

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/djq190PubMedGoogle ScholarCrossref

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.d6397PubMedGoogle ScholarCrossref

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.d6395PubMedGoogle ScholarCrossref

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/NEJMoa2002449PubMedGoogle ScholarCrossref

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
ArticlePubMedGoogle ScholarCrossref

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/NEJMoa1110307PubMedGoogle ScholarCrossref

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.i4218PubMedGoogle ScholarCrossref

44.

Hernán  MA, Robins  JM.  Per-protocol analyses of pragmatic trials.   N Engl J Med. 2017;377(14):1391-1398. doi:10.1056/NEJMsm1605385PubMedGoogle ScholarCrossref


🛈 Nous sommes un collectif de professionnels de la santé, rassemblés en association. Nous agissons et fonctionnons sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
🛈 We are an French non-profit organization of health care professionals. We act our activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
Scroll to Top