Data from Late-Stage Outcomes as Surrogates for Mortality in Cancer Screening Trials: A Systematic Review and Meta-analysis
Year: 2025
Type: other
Abstract: Late-stage cancer incidence has been proposed as a surrogate outcome for cancer-specific mortality in future screening trials. Two previous meta-analyses with 33 and 39 trials assessed trial-level surrogacy but provided inconsistent conclusions about the suitability of late-stage cancer endpoints replacing mortality. Our systematic review and meta-analysis (PROSPERO ID, CRD42023369320) investigated the association between the effect of cancer screening on the incidence of late-stage cancer and cancer-specific mortality. From 57 trials with 61 trial arm comparisons, correlation between late-stage incidence and mortality outcomes was 0.69 [95% confidence interval (CI), 0.47–0.84] for all cancers combined. Specifically, correlations were 0.58 (95% CI, 0.27–0.93) for bowel (N = 11 trials), 0.79 (95% CI, 0.49–0.94) for breast (N = 13), and 0.91 (95% CI, 0.84–0.96) for lung cancer (N = 14). Trial point estimates of the screening effect on mortality were within each trial’s 95% CI late-stage incidence estimates in 56 of 61 (92%) trial arm comparisons and in 16 of 19 (84%) trial arm comparisons in which the entire 95% CI for screening effect on late-stage incidence was below one. Evidence suggests potential for late-stage cancer incidence as a key outcome in screening trials, but further research is needed to clarify when to measure late-stage outcomes, extrapolation for cancer types without trials, and the conditions when late-stage cancer does not accurately predict mortality.
Authors: Matejka Rebolj, Adam R. Brentnall, Julia Geppert, Nefeli Kouppa, Bethany Shinkins, Karoline Freeman, Chris Stinton, Matthew J. Randell, Samantha Johnson, Robert A. Smith, Peter Sasieni, Sam M. Janes, Ruth Etzioni, Stephen W. Duffy, Sian Taylor-Phillips
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7084578916
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