# Let MCED trials read out on late-stage incidence, with mortality follow-up mandated

Source: https://onco.cc/ideas/idea-prev-mced-stage-endpoint-surrogate/  
OnCo record `idea-prev-mced-stage-endpoint-surrogate` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Multi-cancer early detection blood tests take a decade to prove they save lives. Regulators could accept a fall in late-stage cancers as the first answer, validated against pooled data from completed screening trials, provided approval is conditional on continued mortality follow-up.

## Summary

NHS-Galleri chose stage III/IV incidence as its primary endpoint; regulators have not said whether that suffices for approval or coverage. Propose a formal surrogate-validation exercise pooling individual data from completed screening RCTs (NLST, NELSON, UKCTOCS, ERSPC, Minnesota, NordICC) to estimate the trial-level correlation between late-stage incidence reduction and cancer-specific mortality reduction, and a conditional-approval pathway with mandated mortality follow-up.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Across historical screening RCTs, the trial-level relative reduction in stage III/IV incidence predicts cancer-specific mortality reduction well enough (R-squared above 0.7) that a pre-specified late-stage incidence threshold can serve as a conditional endpoint.
- Rationale: UKCTOCS is the cautionary case: it shifted stage without reducing mortality because the ovarian cancers that shifted were still lethal. A pooled analysis would quantify when stage shift does and does not translate, per cancer, instead of arguing by anecdote.
- Proposed test: Individual-patient-data meta-analysis of screening RCTs (two years, small budget); then FDA/MHRA guidance on conditional MCED approval; NHS-Galleri and the NCI Vanguard study as first users.
- Maturity: speculative
- Actor: regulator

## Sources

- NHS-Galleri trial: https://www.nhs-galleri.org
- CISNET: https://cisnet.cancer.gov

## Connected records

- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- drugs: [Galleri](https://onco.cc/drugs/galleri/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/), [Stage shift](https://onco.cc/terms/stage-shift/)
- trials: [NHS-Galleri](https://onco.cc/trials/nhs-galleri/), [PATHFINDER 2](https://onco.cc/trials/pathfinder-2/)
- bottlenecks: [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test](https://onco.cc/key-papers/paper-nhs-galleri-design-cancers-2022/), [Prasad: most surrogate endpoints in cancer trials correlate poorly with survival](https://onco.cc/key-papers/paper-prasad-surrogate-endpoints-jama-im-2015/)

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