Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct;8(13):6127-6138.
doi: 10.1002/cam4.2476. Epub 2019 Aug 18.

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study

Eveline A M Heijnsdijk  1 , Marcell Csanádi  2 , Andrea Gini  1 , Kevin Ten Haaf  1 , Rita Bendes  2 , Ahti Anttila  3 , Carlo Senore  4 , Harry J de Koning  1
Affiliations

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study

Eveline A M Heijnsdijk et al. Cancer Med. 2019 Oct.

Abstract

Background: All-cause mortality has been suggested as an end-point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow-up is needed to find a significant reduction in all-cause mortality.

Methods: A literature review was conducted to identify previous studies that modeled the effect of screening on all-cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer-specific deaths, all-cause deaths, and life-years gained per year of follow-up.

Results: There were large differences between the evaluated cancers. For lung cancer, when 40 000 high-risk people are randomized to each arm, a significant reduction in all-cause mortality could be expected between 11 and 13 years of follow-up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow-up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15-20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.

Conclusion: Cancer screening trials are able to demonstrate a significant reduction in all-cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000-600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all-cause mortality can only be detected between specific years of follow-up, more limited than the timeframe to detect a reduction in cancer-specific mortality.

Keywords: breast; cancer screening; colorectal; evaluation; lung; mortality reduction; trial.

PubMed Disclaimer

Conflict of interest statement

All authors declare: Dr Heijnsdijk, Dr Gini, Csanádi, Bendes, Dr Senore, Dr Anttila report grants from EU‐Framework Programme (Horizon 2020; Number 634753, PI: H.J. de Koning) of the European Commission, during the conduct of the study. Dr ten Haaf and Dr de Koning report grants and nonfinancial support from NELSON‐Netherlands‐Leuven Lung Cancer Screening, grants from NIH/National Cancer Institute, nonfinancial support from International Association for the Study of Lung Cancer Strategic Screening Advisory Committee, grants from Sunnybrook Health Sciences, Toronto, Canada, grants from University of Zurich, Switzerland, outside the submitted work.

Figures

Figure 1
Figure 1
PRISMA flow diagram of the systematic literature review
Figure 2
Figure 2
The period of follow‐up in which a significant difference in lung cancer mortality (gray and black bars) or all‐cause mortality (black bars) can be found by number of high‐risk people (men and women who smoked at least 30 pack‐years and who currently smoke or quit less than 15 years ago) in each arm
Figure 3
Figure 3
The period of follow‐up in which a significant difference in breast cancer mortality (gray and black bars) or all‐cause mortality (black bars) can be found by number of women in each arm
Figure 4
Figure 4
The period of follow‐up in which a significant difference in colorectal cancer mortality (gray and black bars) or all‐cause mortality (black bars) can be found by number of people in each arm using flexible sigmoidoscopy once in a lifetime in the screened arm
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Black WC, Haggstrom DA, Welch HG. All‐cause mortality in randomized trials of cancer screening. J Natl Cancer Inst. 2002;94(3):167‐173. - PubMed
    1. Interventions IWGotEoC‐P , ed. Breast cancer screening. Lyon: International Agency for Research on Cancer; 2016. - PubMed
    1. Gøtzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2013;6:CD001877. - PMC - PubMed
    1. Penston J. Should we use total mortality rather than cancer specific mortality to judge cancer screening programmes? Yes. BMJ. 2011;343:d6395. - PubMed
    1. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013;108(11):2205‐2240. - PMC - PubMed

Publication types