Recommendations of the American Cancer Society workshop on design, conduct, analysis, and reporting of multicancer early detection trials with late-stage incidence end points and post-trial ongoing evaluation-The Peachtree Consensus.

backgroundIn a new era of multicancer early detection (MCED), late-stage incidence has been proposed as an end point for the evaluation of test efficacy, marking a departure from the established end point of cancer mortality.

methodsThe American Cancer Society convened a panel of 15 academic researchers with expertise in cancer screening evaluation to develop principles assuring the validity and interpretability of MCED trials with late-stage incidence end points and advancing implementation of tests with potential for meaningful clinical utility.

resultsThe definition of late-stage cancer is critical and affects study design, interpretation, and outcomes. The authors of the Peachtree Consensus recommend considering cancer-type-specific definitions of late stage and paying attention to comparability of staging intensity in both trial arms. The duration of screening and the follow-up interval after the last screen should be chosen based on the preclinical early stage and late-stage durations of the target cancer types. The authors also recommend reporting aggregate results and results for individual cancer types as numbers permit and summarizing relative and absolute benefits. Predicted mortality reductions should be calculated to contextualize a late-stage result and the inputs and assumptions involved should be reported. Given a significant late-stage reduction suggestive of meaningful clinical benefit, the authors support launching consortium and demonstration studies while continuing to track trial mortality outcomes.

conclusionsTrials with late-stage incidence end points that are conducted using these principles should support the development of evidence-based screening guidelines as well as the creation of accessible data resources for observational and modeling studies.