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
. 2023 Jul;129(1):72-80.
doi: 10.1038/s41416-023-02243-9. Epub 2023 Apr 25.

Modelled mortality benefits of multi-cancer early detection screening in England

Peter Sasieni  1 , Rebecca Smittenaar  2 , Earl Hubbell  3 , John Broggio  4 , Richard D Neal  5 , Charles Swanton  6   7
Affiliations

Modelled mortality benefits of multi-cancer early detection screening in England

Peter Sasieni et al. Br J Cancer. 2023 Jul.

Erratum in

Abstract

Background: Screening programmes utilising blood-based multi-cancer early detection (MCED) tests, which can detect a shared cancer signal from any site in the body with a single, low false-positive rate, could reduce cancer burden through early diagnosis.

Methods: A natural history ('interception') model of cancer was previously used to characterise potential benefits of MCED screening (based on published performance of an MCED test). We built upon this using a two-population survival model to account for an increased risk of death from cfDNA-detectable cancers relative to cfDNA-non-detectable cancers. We developed another model allowing some cancers to metastasise directly from stage I, bypassing intermediate tumour stages. We used incidence and survival-by-stage data from the National Cancer Registration and Analysis Service in England to estimate longer-term benefits to a cohort screened between ages 50-79 years.

Results: Estimated late-stage and mortality reductions were robust to a range of assumptions. With the least favourable dwell (sojourn) time and cfDNA status hazard ratio assumptions, we estimated, among 100,000 screened individuals, 67 (17%) fewer cancer deaths per year corresponding to 2029 fewer deaths in those screened between ages 50-79 years.

Conclusion: Realising the potential benefits of MCED tests could substantially reduce late-stage cancer diagnoses and mortality.

PubMed Disclaimer

Conflict of interest statement

PS is a paid member of GRAIL’s Scientific Advisory Board and the Director of the The Cancer Research UK and King’s College London Cancer Prevention Trials Unit that is contracted by GRAIL, LLC, to run the NHS-Galleri trial, is on the Medical Advisory Committee for NSV, and has received consultant fees from Roche. RS and EH are employees of GRAIL Bio UK Ltd, and hold stock in Illumina, Inc.; RS also has contingent value rights in GRAIL. JB is employed by NHS Digital and is an Associate Research Fellow (honorary) at the Nuffield Department for Population Health, University of Oxford. RDN provides his services as Co-Chief Investigator to the NHS-Galleri trial through university consultancy funded by GRAIL, LLC, to the University of Exeter; both he and the University of Exeter financially benefit from this partnership. CS provides his services as Co-Chief Investigator to the NHS-Galleri trial through university consultancy funded by GRAIL, LLC, to University College London Business, for another study; is an AstraZeneca advisory board member and Chief Investigator for the AZ MeRmaiD 1 and 2 clinical trials; CS is a paid member of GRAIL’s Scientific Advisory Board (SAB); received grant funding from AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Pfizer, Roche-Ventana, Invitae, and Ono Pharmaceutical; receives consultant fees from Achilles Therapeutics (also SAB member), Genentech, Medixci, Roche Innovation Centre Shanghai, Bicycle Therapeutics (also SAB member), Metabomed (until July 2022), and the Sarah Cannon Research Institute; has received honoraria from Amgen, AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, Illumina, and Roche-Ventana; had stock options in Apogen Biotechnologies and GRAIL until June 2021; currently has stock options in Epic Bioscience, Bicycle Therapeutics, and Achilles Therapeutics; and is co-founder of Achilles Therapeutics.

Figures

Fig. 1
Fig. 1. Interception model schematic.
Before a single prevalent round of screening, cancer a was shedding cell-free DNA (cfDNA) at stage I and progressed to stage III, when it was intercepted; b became cfDNA shedding at stage II and progressed to stage IV, when it was intercepted; c became cfDNA shedding at stage II, when it was intercepted; d was not shedding cfDNA at stage I when it was screened in a prevalent screening round, and progressed to stage III before it was intercepted in the incident screening round; e became cfDNA shedding at stage I and did not progress before being intercepted at the incident screening round; f never became cfDNA-detectable, was not intercepted by MCED screening, and presented in usual care at stage IV; and g became cfDNA-detectable at stage II and progressed to stage III between screening rounds, when it was detected via usual care.
Fig. 2
Fig. 2. Survival by cfDNA status and stage for selected cancer types.
This figure shows observed five-year survival data for cancers diagnosed between 2013 and 2018, as registered by the National Cancer Registration and Analysis Service (NCRAS), and modelled five-year survival data based on cfDNA detectability status (hazard ratio [HR] = 3). For visualisation purposes, we plotted net survival for a 65-year-old in the middle of the screening programme, and data has been smoothed. Where the lines representing cfDNA+/− survival are not visible, they are (almost) identical to that of original survival. For a small number of cancers at specific stages, adjustment of survival data for both cfDNA-detectable and cfDNA-non-detectable cases to reflect the observed survival in the population created implausible results, in which later-stage survival for cfDNA-detectable cancers was favourable compared with that of earlier-stage cancers. This occurred when there was a large difference in test sensitivity between one stage and the next, such that applying the HR to the different cfDNA populations moved the survival curves further out from the observed mean. We did not correct for this anomaly, as it was only ever a difference of a few percentage points, and it would have decreased the average observed survival-by-stage.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. - PubMed
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. - PubMed
    1. Office for National Statistics. Population estimates. https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigrati.... Accessed 22 November 2022.
    1. Office for National Statistics. Total cancer deaths in the UK in 2019 and 2020. https://www.ons.gov.uk/aboutus/transparencyandgovernance/freedomofinform.... Accessed 23 November 2022.
    1. NHS Digital. Cancer survival in England, cancers diagnosed 2015 to 2019, followed up to 2020. https://digital.nhs.uk/data-and-information/publications/statistical/can.... Accessed 22 November 2022.

Publication types