eprintid: 10206230 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/20/62/30 datestamp: 2025-03-17 16:25:07 lastmod: 2025-03-17 16:27:26 status_changed: 2025-03-17 16:25:07 type: article metadata_visibility: show sword_depositor: 699 creators_name: Callender, Thomas creators_name: Payne, Katherine creators_name: Pashayan, Nora creators_name: Mackie, Anne title: Screening for multiple cancers: evaluation must go beyond aggregate measures ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: D12 divisions: K71 divisions: G21 note: This version is the author-accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: Tom Callender and colleagues argue that aggregate outcomes amongst groups of cancers are insufficient for the evaluation of multi-cancer detection tests for cancer screening and that research providing cancer-specific outcomes will be necessary. Multi-cancer detection tests (MCDs) using blood-based biomarkers for the concurrent screening of multiple cancer types in asymptomatic individuals are currently being trialled in the UK and elsewhere [1]. This has led to talk of their adoption in early cancer population screening programmes. Considerable attention has been paid to the potential benefits that MCDs could present by improving cancer survival, particularly that of rarer cancers, through early detection. Balanced against these benefits has been a focus on the possible harms from false positives; inaccurate predictions of, or indeed inability to, predict the cancer site; and cases where a cancer is detected by an MCD but is too small to be seen on imaging [2,3]. Most discussion has considered the overall – aggregate – benefits and harms of an MCD programme. However, cancers behave remarkably differently both between individuals and cancer types. Despite this, the benefits and harms accruing to each type of cancer with strategies that uses a single multi-cancer screening test has had relatively little emphasis. In this analysis, we discuss how differences in disease natural history could affect one potential harm, overdiagnosis, when screening for multiple cancers simultaneously. We argue that a focus on aggregate, all-cancer, metrics to evaluate MCDs will obscure differences between cancers that are clinically and policy relevant. Building on this, we discuss the benefits and challenges of approaches that balance the translation of a promising MCD screening programme against the further research that may be required to inform robust policy. date: 2025-02-25 date_type: published publisher: BMJ Publishing Group official_url: https://doi.org/10.1136/bmj-2024-081098 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2365737 doi: 10.1136/bmj-2024-081098 medium: Electronic lyricists_name: Callender, Thomas lyricists_name: Pashayan, Nora lyricists_id: TCALL19 lyricists_id: NPASH45 actors_name: Kaltenbacher, Brigitte G actors_id: BGKAL87 actors_role: owner full_text_status: public publication: The BMJ volume: 388 article_number: e081098 event_location: England issn: 0959-535X citation: Callender, Thomas; Payne, Katherine; Pashayan, Nora; Mackie, Anne; (2025) Screening for multiple cancers: evaluation must go beyond aggregate measures. The BMJ , 388 , Article e081098. 10.1136/bmj-2024-081098 <https://doi.org/10.1136/bmj-2024-081098>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10206230/1/Callender1_overdiagnosis-manuscript-r3-clean.pdf