Elsevier

European Urology

Volume 62, Issue 5, November 2012, Pages 745-752
European Urology

Platinum Priority – Prostate Cancer
Editorial by Allison S. Glass, Matthew R. Cooperberg and Peter R. Carroll on pp. 753–755 of this issue
Screening for Prostate Cancer Decreases the Risk of Developing Metastatic Disease: Findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC)

https://doi.org/10.1016/j.eururo.2012.05.068Get rights and content

Abstract

Background

Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal.

Objective

To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial.

Design, setting, and participants

Data were available for 76 813 men aged 55–69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up.

Intervention

Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm.

Outcome measurements and statistical analysis

The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease.

Results and limitations

After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60–0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41–0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up.

Conclusions

PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases.

The ERSPC trial is registered under number ISRCTN49127736.

Introduction

Screening for prostate cancer (PCa) remains controversial, even after the European Randomized Study of Screening for Prostate Cancer (ERSPC) [1], [2] reported a 21% relative reduction of deaths from PCa at 11 yr of follow-up and the Gothenburg (Sweden) trial, one of the ERSPC centers, showed 44% reduction at 14 yr [3]. The main reason for controversy concerns the harms associated with PCa screening, such as the high risk of overdiagnosis and overtreatment [4].

The occurrence of metastatic disease is a very important contributor to the suffering caused by PCa. Its prevention or delay is a legitimate secondary end point of screening. Earlier studies have reported that early diagnosis by prostate-specific antigen (PSA) testing results in a reduction of the number of men with metastatic disease [5], [6], [7]. The ERSPC study has shown a 41% decrease of metastatic disease in the screening arm at the time of diagnosis [1]; however, progression to metastatic disease during follow-up after initial treatment that was not evaluated in the ERSPC study [1] should also be influenced by screening.

The goal of this paper is to compare the incidence of metastatic disease, not only at diagnosis but also during subsequent follow-up, in the screening and control arms of four major centers of the ERSPC study group.

Section snippets

Materials and methods

The ERSPC is a randomized trial comparing an intervention arm of men to whom regular PSA screening is offered with a control arm to which such screening is not offered. Details of the methodology have been described previously for all centers in the ERSPC study [1] and for the Gothenburg trial by Hugosson et al. [3]. In all centers, known cases of PCa were excluded before randomization. The Swedish center utilized a 2-yr screening interval, whereas a 4-yr interval was applied at the other

Results

The study population is shown in Figure 1, which also shows the part of the total ERSPC population that is included in the present report. In addition, absolute numbers of participants, cancers and M+ cases diagnosed, and deaths per arm are shown. The numbers of participants in the screening and control arms, the numbers of men with M+ disease per center and per study arm, and the relative risks of M+ at diagnosis and during follow-up are specified in Table 1. The follow-up periods differed

Discussion

Our results show an absolute risk reduction of 3 M+ PCa cases per 1000 men, corresponding to a relative risk reduction of 30% (p = 0.001) in favor of screening. This reduction in M+ disease must be balanced against the downside of screening, mainly the rate of overdiagnosis in the screening arm, estimated at ≥50% in the setting of the ERSPC [4]; in the current analysis, a potential rate of overdiagnosis of 55.6% was shown. This report is next to that of Kilpeläinen et al. [10], which is limited

Conclusions

Our study shows relative reductions of 30% and 42% in M+ disease by screening for the whole population and for men who are screened, respectively, after 12 yr of follow-up. This benefit must be balanced against potential harms of screening.

References (11)

There are more references available in the full text version of this article.

Cited by (199)

View all citing articles on Scopus

Please visit www.eu-acme.org/europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.

View full text