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Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer
European Urology 2015 Mar 16 [Epub ahead of print]
The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality.
Design, setting, and participants
Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis.
Outcome measurements and statistical analysis
Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis.
Results and limitations
In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03–2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16–1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89–1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52–0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller.
The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr.
The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.
Keywords: Prostate screening, PSA, Metastatic cancer incidence, Mortality reduction.
a Clinical and Descriptive Epidemiology and Registries Unit, ISPO – Cancer Research and Prevention Institute, Florence, Italy
b School of Health Sciences, University of Tampere, Tampere, Finland
c Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
d Department of Urology, Sahlgrenska Academy at University of Gothenburg, Sweden
e Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA
f Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
g Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands
h Oncological Centre Antwerp, Belgium
i Department of Urology, Kantonsspital Aarau, Aarau, Switzerland
j Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany
k Urology Department, Hospital Infanta Cristina, Parla, Madrid, Spain
l Provinciaal Instituut voor Hygiene, Antwerp, Belgium
m Department of Urology, Hospital Universitario de Fuenlabrada, Madrid, Spain
n Department of Urology University Hospital Zürich, Zürich, Switzerland
o Department of Urology, Clinique BeauSoleil – EA2415, Montpellier, France
p Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland
q Department of Urology, CHU Lille, Univ Lille Nord de France, Lille, France
© 2015 Published by Elsevier B.V.