Elsevier

The Lancet Oncology

Volume 11, Issue 8, August 2010, Pages 725-732
The Lancet Oncology

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Mortality results from the Göteborg randomised population-based prostate-cancer screening trial

https://doi.org/10.1016/S1470-2045(10)70146-7Get rights and content

Summary

Background

Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.

Methods

In December, 1994, 20 000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10 000) or to a control group not invited (n=10 000). Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243.

Findings

In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12·7% in the screening group and 8·2% in the control group (hazard ratio 1·64; 95% CI 1·50–1·80; p<0·0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0·40% (95% CI 0·17–0·64), from 0·90% in the control group to 0·50% in the screening group. The rate ratio for death from prostate cancer was 0·56 (95% CI 0·39–0·82; p=0·002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0·44 (95% CI 0·28–0·68; p=0·0002). Overall, 293 (95% CI 177–799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death.

Interpretation

This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs.

Funding

The Swedish Cancer Society, the Swedish Research Council, and the National Cancer Institute.

Introduction

The European Randomised Study of Screening for Prostate Cancer (ERSPC) compared a group of men invited for prostate-cancer screening based on prostate-specific antigen (PSA) with a control group without any active intervention. Interim analyses, based on a median follow-up of 9 years,1, 2 showed that men randomised to active screening had a significant reduction in prostate-cancer mortality; rate ratio (RR) 0·80 (95% CI 0·65–0·98, adjusted p=0·04).1 The number of men needed to be screened (NNS) to prevent one death from prostate cancer was 1410 (or 1068 in men who were actually screened1), which is similar to breast and colorectal cancer screening.3, 4, 5, 6 However, the number of men needed to treat (NNT) to prevent one death was high (48 men), which might be explained by only 9 years of follow-up or by screening that resulted in the detection of a large proportion of indolent cancers.

These reports provide the first level one evidence that PSA-based prostate-cancer screening can reduce prostate-cancer mortality. An open question, however, is whether the modest benefit in reduced cancer mortality documented thus far outweighs the harms of over-detection. This issue is emphasised by the report from another large screening trial, the US-based Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial, which found no difference in prostate-cancer mortality between men randomised to screening and those in the control group at 11·5 years of follow-up.7 Other randomised studies have either been too small8, 9 or criticised for methodological problems.10, 11

The Göteborg randomised population-based prostate-cancer screening trial is a prospective randomised trial, planned and started in 1995, assessing the effects of PSA-based screening every 2 years. The trial is truly population-based, as individuals from the population register were randomised to screening or control groups without prior information, which results in a more representative study than randomisation after informed consent. The study design allows the analysis of both how a screening programme will be accepted by the population and its effectiveness in terms of prostate-cancer mortality reduction at a population level. The trial was designed and initiated independently from the ERSPC, although it was subsequently agreed to include a subset of participants in the ERSPC. According to the ethical committee approval from 1994, an analysis of this study was planned for after 15 years. The present report is the first publication from the Göteborg trial assessing prostate-cancer mortality.

Section snippets

Participants

As of Dec 31, 1994, the population register documented 32 298 men born between 1930 and 1944 (age 50–64, median 56 years) living in the city of Göteborg, Sweden. By computer randomisation 20 000 of these men were identified and allocated to either the intervention arm (screening group) or to a control group. The number of men in each birth cohort (1930–34, 1935–39, and 1940–44) was calculated to be proportional to the distribution in the original cohort. This resulted in larger birth cohorts

Results

The trial profile is shown in figure 1. Subsequent to randomisation, we excluded from analysis 56 men with a prior diagnosis of prostate cancer, 34 who had died, and six who had emigrated but had not been removed from the population register at the time of randomisation. Thus, the screening and control groups each consisted of 9952 evaluable men. In the screening group, 7578 (76%) of 9952 men participated in at least one screening round (attendees; table 1). These men received 29 315 PSA tests

Discussion

The aim of this prospective, population-based randomised screening study was to assess the effectiveness of a screening programme in which men were first randomised and then asked to participate. The design gives more representative results than does randomisation after informed consent, and mirrors the situation when screening is introduced in the population. The study yielded two major findings. First, a PSA-based screening programme is acceptable to men aged 50 years or older, with 76%

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