Abstract
Background: Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Methods: Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Results: Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Conclusion: Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.
| Original language | English |
|---|---|
| Journal | JOURNAL OF MEDICAL SCREENING |
| Volume | 28 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2021 |
| Publication type | A1 Journal article-refereed |
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: JL, SVC, RG, and RE were supported by a grant from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modelling Network (U01-CA199338-02). RG was also supported by the National Cancer Institute (R50-CA221836).SVC’s work on this paper was supported in part by a Cancer Center Support Grant from the National Cancer Institute made to Memorial Sloan Kettering Cancer Center (P30-CA008748), a Specialized Program Of Research Excellence (SPORE) grant from the National Cancer Institute to Dr. H. Scher (P50-CA092629), and a career development award from the National Cancer Institute (K22-CA234400). JCH’s work was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. RE’s work is partially supported by the Rosalie and Harold Rea Brown Endowment. The funding bodies had no role in the preparation, review, or approval of the manuscript or the decision to submit the manuscript for publication. The funding of the ERSPC trial was obtained from national cancer research funding agencies, European funding in the form of Framework programs, private sponsors, and a grant from the former Beckman/Hybritech company. The maintenance of the ERSPC central database is sponsored by the European Association of Urology.
Keywords
- European Randomized Study of Screening for Prostate Cancer
- metastasis
- Prostate cancer
- screening
- simulation model
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Health Policy
- Public Health, Environmental and Occupational Health
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