Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials
Open accessAbstract
BACKGROUND: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. OBJECTIVE: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. DESIGN: Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. SETTING: Randomized controlled trials in Europe and the United States. PARTICIPANTS: Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. INTERVENTION: Prostate cancer screening. MEASUREMENTS: Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. RESULTS: Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. LIMITATION: The MLT is a simple metric of screening and diagnostic work-up. CONCLUSION: After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. PRIMARY FUNDING SOURCE: National Cancer Institute.
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The decreases in prostate cancer mortality in high-income countries likely reflect advancements in effective treatment and earlier detection through increased testing of asymptomatic men.
“likely reflecting advancements in effective treatment and earlier detection through increased testing of asymptomatic men.101,102”
From Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. (2024) · cites this paper as [101]
The Results and Discussion (page not specified in our copy) find that PSA screening reduces the risk of prostate cancer death, supporting the earlier-detection component. The paper does not establish that mortality declines across high-income countries resulted from increased testing of asymptomatic men or advances in treatment; it treats treatment differences as a possible factor in trial baseline risks. (LLM, conf=0.86)
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References 19 · Cited by 251
Research works printed but not linked: 1
- [11]Melnikow J LeFevre ML Wilt TJ Moyer VA Randomized Trials Provide the Strongest Evidence for Clinical Guidelines: The US Preventive Services Task Force and Prostate Cancer Screening Medical Care 2013 51 4 301 3 23481031
- Authors
- Tsodikov, A., Gulati, R., Heijnsdijk, E. A. M., Pinsky, P. F., Moss, S. M., Qiu, S., de Carvalho, T. M., Hugosson, J., Berg, C. D., Auvinen, A., Andriole, G. L., Roobol, M. J., Crawford, E. D., Nelen, V., Kwiatkowski, M., Zappa, M., Luján, M., Villers, A., Feuer, E. J., de Koning, H. J., Mariotto, A. B., & Etzioni, R.
- Affiliations
- Universidad Complutense de Madrid (ES)
- From University of Michigan, Ann Arbor, Michigan; Fred Hutchinson Cancer Research Center, Seattle, Washington; Erasmus Medical Center, Rotterdam, the Netherlands; National Cancer Institute, Bethesda, Maryland; Queen Mary University of London, London, United Kingdom; Sahlgrenska University Hospital, Göteborg, Sweden; Johns Hopkins Medicine, Baltimore, Maryland; University of Tampere, Tampere, Finland; Washington University School of Medicine, St. Louis, Missouri;
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2017-10-03
- Volume
- 167
- Issue
- 7
- Pages
- 449-455
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC5734053
- OpenAlex
- W2762223230
- Cited by
- 251
- References
- 19
- Citations by year
- 2026: 22 · 2025: 24 · 2024: 33 · 2023: 18 · 2022: 24 · 2021: 25 · 2020: 31 · 2019: 23 · 2018: 48 · 2017: 3
- FWCI
- 23.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (U01CA157224, UM1CA182883, U10CA180834, U01CA199338)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- prostate cancer screening, prostate cancer mortality, European Randomized Study of Screening for Prostate Cancer, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, screening effects, prostate cancer incidence, diagnostic workup, trial comparability
- MeSH terms
- Aged, Europe, Humans, Male, Mass Screening, Middle Aged, Prostatic Neoplasms, Time Factors, United States, Incidence, Proportional Hazards Models, Randomized Controlled Trials as Topic, Early Detection of Cancer
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