Elsevier

The Lancet

Volume 384, Issue 9959, 6–12 December 2014, Pages 2027-2035
The Lancet

Articles
Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up

https://doi.org/10.1016/S0140-6736(14)60525-0Get rights and content

Summary

Background

The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years.

Methods

ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736.

Findings

With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 [1·58–1·69] including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88).

Interpretation

In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.

Funding

Each centre had its own funding responsibility.

Introduction

The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years1 and 11 years of follow-up.2 Despite these results, screening for prostate cancer is controversial because of adverse effects such as overdiagnosis, which is estimated to include 40–50% of screen-detected cases and often results in overtreatment with subsequent side-effects.3, 4, 5 However, a modelling study, partly based on ERSPC data, showed that with a 4-year screening interval a gain of 52 life-years and a gain of 41 quality-of-life-adjusted life-years (QALYs) was achieved per 1000 men, despite some reduction in quality of life due to overdiagnosis and long-term side-effects of treatment.5

We report updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9 years, 11 years, and 13 years of follow-up. For the first time, we include France in the analysis of incidence of prostate cancer at 9 years of follow-up, but not in the analysis of mortality because of incomplete follow-up to the end of 2010.

Section snippets

Study design and participants

The ERSPC is a multicentre, randomised, screening trial with the main aim to compare mortality from prostate cancer in an intervention group invited to screening with a control group with no intervention offered. The trial was initiated in 1993 in the Netherlands and in Belgium.6, 7 Five other centres (in Sweden, Finland, Italy, Spain, and Switzerland) joined the study between 1994 and 1998. Two French centres started in 2000 and 2003.

Eligible participants were men aged 50–74 years at the time

Results

In the core group of men aged 55–69 years, excluding France, 162 388 were randomly assigned, of whom 145 died between randomisation and screening. With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group (figure 1).

The median age at randomisation was 60·2 years (table 1). The overall compliance with biopsies was 85·6%, 20 188 of 23 574 screen-positive tests. On average, men in the intervention group

Discussion

The results of our primary analysis, based on extended follow-up up to 13 years, showed no further increase in the relative effect of screening on prostate cancer mortality after 11 years,2 but an enhanced absolute mortality reduction per 1000 men randomised (panel). In line with ERSPC rules of participation and reporting,8 France was included in the analysis of incidence, but not in that of mortality, because of incomplete follow-up to the end of 2010. The absolute effect—ie, absolute risk

References (29)

  • FH Shröder et al.

    European randomized study of screening for prostate cancer—the Rotterdam pilot studies

    Int J Cancer

    (1996)
  • FH Schröder et al.

    European randomized study of screening for prostate cancer. Progress report of Antwerp and Rotterdam pilot studies

    Cancer

    (1995)
  • PH Gann et al.

    A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer

    JAMA

    (1995)
  • Study protocol ERSPC. Last updated Sept 10, 1998

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