Elsevier

European Urology

Volume 76, Issue 1, July 2019, Pages 43-51
European Urology

Platinum Priority – Prostate Cancer – Editor's Choice
Editorial by Gunnar Steineck, Olof Akre and Anna Bill-Axelson on pp. 52–53 of this issue
A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer

https://doi.org/10.1016/j.eururo.2019.02.009Get rights and content

Abstract

Background

The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.

Objective

To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.

Design, setting, and participants

This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55–69 yr), selected from population registry.

Outcome measurements and statistical analysis

The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.

Results and limitations

The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72–0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently.

Conclusions

Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.

Patient summary

In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.

Introduction

The European Randomized study of Screening for Prostate Cancer (ERSPC) was initiated in 1993, with the primary aim to investigate the effect of regular prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality. Findings were previously reported on three occasions, as prespecified in the study protocol at 9, 11, and 13 yr of follow-up [1], [2], [3]. The latest report (2014) showed that PSA screening increased PCa incidence 1.6-fold and the relative reduction in PCa mortality was 21% at 13 yr of follow-up [3]. This is the 16-yr main endpoint follow-up in order to quantify the long-term harms and benefits of screening. Secondary aims were to investigate how variations in screening attendance and duration of screening (one test only vs repeated testing) affected PCa mortality and whether this could explain the observed variations in outcome between different screening trials as well as between different ERSPC centres [3], [4].

Section snippets

Study design and participants

The ERSPC, described previously [1], [2], [3], is a multicentre randomised screening trial for PCa in eight European countries (Fig. 1). It started in Belgium and the Netherlands (1993), and the last country to join was France in 2003. Minor variations in screening protocols between centres were accepted, but compulsory criteria for participation were defined [5], including PSA as the primary screening test, followed by systematic prostate biopsies for men with elevated PSA; a core age group of

Primary analyses

A total of 182 160 men were randomised, of whom 162 389 were part of the core age group of men 55–69 yr old. Figure 1 shows the trial profile. Men randomised to the screening arm were screened on average 1.94 times (2.3 times in screening attendees), and of those participating, 28% were screen positive at least once (Table 1). Median follow-up (excluding France; from randomisation to a minimum of 16 yr, December 31, 2014, and the date of death) was 15.5 yr and median follow-up from diagnosis to PCa

Discussion

This ERSPC update with 3 additional years of follow-up shows that the absolute reduction in PCa mortality still increases with longer duration of follow-up, while the relative risk reduction remains unchanged at 20% since the initial report based on 8.8 yr of follow-up [1], [2], [3]. PCa incidence in the control group is gradually catching up with the screening arm, but at 16 yr, a 41% excess incidence remains in the screening arm. Results illustrate that both incidence and mortality differences

Conclusions

This 16-yr report from ERSPC shows that the absolute effect of screening on PCa mortality increases with longer follow-up. The excess PCa incidence among screened men is decreasing but is still rather high. The PCa mortality reduction seems to be related to the duration of screening, and a one-time screening test is suggested to have little or no effect on PCa mortality due to a prevalence pool of more advanced disease in which treatment is unlikely to provide major benefits.

Author

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