ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2022
Stage Shift as an Endpoint in Cancer Screening Trials: Implications for Evaluating Multicancer Early Detection Tests.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Late-Stage Outcomes as Surrogates for Mortality in Cancer Screening Trials: A Systematic Review and Meta-analysis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Pooled it
- Bias in Meta-Analytic Modeling of Surrogate Endpoints in Cancer Screening Trials.Statistics in medicine · 2026Article
- Can ovarian cancer screening work? A secondary analysis of the UK collaborative trial of ovarian cancer screening.British journal of cancer · 2026Article
- A Quantitative Framework to Assess the Potential of Earlier Cancer Detection to Improve Cancer Survival.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Should Multi-Cancer Early Detection Testing Replace Guideline-Recommended Colorectal Cancer Screening? A Comparative Modeling Analysis.medRxiv : the preprint server for health sciences · 2026Article
- Ten Recommendations for Modelling Cost Effectiveness of Screening: Perspectives of an International Stakeholder Group.PharmacoEconomics · 2026Review
- Improved stage-specific survival in screen-detected breast cancer in Denmark: a cohort study.Journal of the National Cancer Institute · 2026Article
- Impact of Multicancer Screening on Late-Stage Cancer at Diagnosis in Breast Cancer Survivors: A Modeling Study.JCO precision oncology · 2026Article
- Measuring and defining screening benefit in a new era of cancer early detection.Journal of the National Cancer Institute · 2026Article
- Lung cancer screening for never smokers: current evidence and future directions.Singapore medical journal · 2026Review
- Diverging Incidence and Mortality of Cutaneous Melanoma in Mainland China, 1990-2023, with Projections to 2030: A Global Burden of Disease 2023 Analysis.Clinical, cosmetic and investigational dermatology · 2026Article
- Cost-effectiveness of CA125- and age-informed risk-based triage for ovarian cancer detection in primary care.British journal of cancer · 2025Article
- Modeling the Impact of Multicancer Early Detection Tests: A Review of Natural History of Disease Models.Medical decision making : an international journal of the Society for Medical Decision Making · 2025Review
- Clinical Significance of a Multicancer Screening Trial With Stage-Based End Points.JAMA network open · 2025Article
- Insights from age-stratified endoscopic detection metrics support initiating colorectal cancer screening at age 45.BMC gastroenterology · 2025Article
- Article
- Multi-cancer early detection tests: Attributes for clinical implementation.Cancer biomarkers : section A of Disease markers · 2025Article
- Integrating Multi-Cancer Early Detection (MCED) Tests with Standard Cancer Screening: System Dynamics Model Development and Feasibility Testing.PharmacoEconomics - open · 2025Article
- Circulating Tumor DNA in Early and Metastatic Breast Cance-Current Role and What Is Coming Next.Cancers · 2024Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDisease-specific mortality is a consensus endpoint in cancer screening trials. New liquid biopsy-based screening tests, including multi-cancer early detection (MCED) tests, are creating a need to reduce the typically lengthy screening trial process. Endpoints based on the reduction in late-stage disease (stage shift) have been proposed but it is unclear how well they predict the impact of screening on disease-specific mortality across a variety of cancers potentially detectable by MCED tests.
methodsWe develop a mathematical formulation relating the reduction in late-stage cancer to the expected reduction in disease-specific mortality if cases diagnosed early via screening receive a corresponding shift in mortality. We investigate the similarity between the expected mortality reduction and the observed mortality reduction in published trials of screening for breast, lung, ovarian, and prostate cancer.
resultsThe expected mortality reduction for a given stage shift varies significantly depending on cancer- and stage-specific survival distributions, with some cancer types showing little possibility for mortality improvement even under substantial stage shift. The expected mortality reduction fails to consistently match the mortality outcomes of published trials.
conclusionsIn MCED, any mortality benefit is likely to vary substantially across target cancers. Stage shift does not appear to be a reliable basis for inference about mortality reduction across cancers potentially detectable by MCED tests. IMPACT: Stage shift may be an appealing endpoint for evaluation of cancer screening tests but it appears to be an unreliable predictor of mortality benefit; furthermore, the same stage shift can mean different things for different cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.