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Review
. 2024 May;25(5):e183-e192.
doi: 10.1016/S1470-2045(24)00015-9.

Considerations for using potential surrogate endpoints in cancer screening trials

Alexis B Webb  1 , Christine D Berg  2 , Philip E Castle  3 , David Crosby  1 , Ruth Etzioni  4 , Larry G Kessler  5 , Usha Menon  6 , Mahesh Parmar  6 , Robert J C Steele  7 , Peter D Sasieni  8
Affiliations
Review

Considerations for using potential surrogate endpoints in cancer screening trials

Alexis B Webb et al. Lancet Oncol. 2024 May.

Abstract

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

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Conflict of interest statement

Declaration of interests CDB receives consultation fees from Mercy BioAnalytics, Lucid Diagnostics, and Medial Early Sign; and is the Chair of the Independent Data Monitoring Committee of the NHS Galleri Study for GRAIL. DC receives consultation fees from MD Anderson Cancer Center, the São Paulo Research Foundation, and Roche; and received payment or honoraria for lectures with EIT Health and the MD Anderson Cancer Center. UM had stock ownership (2011–21) awarded by University College London in Abcodia, which held the licence for the Risk of Ovarian Cancer Algorithm; reports research collaboration contracts with Cambridge University, QIMR Berghofer Medical Research Institute, Intelligent Lab on Fiber, RNA Guardian, Micronoma, MercyBio Analytics, Imperial College London, University of Innsbruck, and Dana Farber USA; received grant funding from the Medical Research Council (MRC) core funding awards MC_UU_00004/01 and MC_UU_00004/02, MRC Proximity to Discovery Industrial Connectivity Award, Cancer Research UK, the National Institute for Health Research (NIHR) HTA award 16/46/01, NIHR Biomedical Research Centre to University College London Hospitals, The Eve Appeal, the Australian National Health and Medical Research Council, Abcodia, India Alliance, Innovate UK grant, and various research collaborations; has a patent (EP10178345.4) for Breast Cancer Diagnostics; and is a member of Tina's Wish Scientific Advisory Board (USA) and Research Advisory Panel, and Yorkshire Cancer Research (UK). PDS holds grants for the GRAIL NHS Galleri multi-cancer screening study, Cancer Research UK and National Institute of Research BEST4 oesophageal screening trial, and the Yorkshire Cancer Research YORKSURe bladder screening trial; receives consulting fees from GRAIL on its scientific advisory board; is a member of advisory boards for NIHR ARTISTIC-3 (HPV testing in cervical screening), IARC ESTMAPA (triage in cervical screening), and the Yorkshire Cancer Research Yorkshire Lung Screening Trial; is the Chair of the National Cancer Research Institute Screening, Prevention & Early Diagnosis Group; and is the Chair of the NHS England Lung Cancer Screening Group, Cytosponge Implementations Group, and MCED Implementation Group. RE is supported by the National Cancer Institute (grant R35CA274442). PEC, LGK, MP, RJCS, and ABW declare no competing interests.

Figures

Figure
Figure. Timing of potential surrogate endpoint candidates during natural history of cancer
Dotted lines link boxes with potential surrogate endpoints that could be measured at the time of an event to the box denoting occurrence of the event in the progression diagram. Dotted lines around boxes indicate points outside of cancer-related disease (eg, indolent cancers, curative treatment, and death from other causes). NB=Nota bene. X=number.
See this image and copyright information in PMC

References

    1. 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;382:503–13. - PubMed
    1. Shaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG clinical guidelines: colorectal cancer screening 2021. Am J Gastroenterol. 2021;116:458–79. - PubMed
    1. Fitzgerald RC, di Pietro M, O’Donovan M, et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett’s oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet. 2020;396:333–44. - PMC - PubMed
    1. Abderrahman B. Exhaled breath biopsy: a new cancer detection paradigm. Future Oncol. 2019;15:1679–82. - PubMed
    1. Fitzgerald RC, Antoniou AC, Fruk L, Rosenfeld N. The future of early cancer detection. Nat Med. 2022;28:666–77. - PubMed

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