Clinical Consequences of Screening for Prostate Cancer: 15 Years Follow-up of a Randomised Controlled Trial in Sweden

Abstract

Objective:

To test the feasibility of a population-based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period.

Methods:

From the total population of men aged 50–69 years in Norrköping (n = 9026) every sixth man (n = 1494) was randomly selected to be screened for prostate cancer every third year over a 12-year period. The remaining 7532 men were treated as controls. In 1987 and 1990 only digital rectal examination (DRE) was performed, in1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen (PSA). TNM categories, grade of malignancy, management and cause of death were recorded in the South-East Region Prostate Cancer Register.

Results:

There were 85 (5.7%) cancers detected in the screened group (SG), 42 of these in the interval between screenings, and 292 (3.8%) in the unscreened group (UG). In the SG 48 (56.5%) of the tumours and in the UG 78 (26.7%) were localised at diagnosis (p < 0.001). In the SG 21 (25%) and in the UG 41 (14%) received curative treatment. There was no significant difference in total or prostate cancer-specific survival between the groups.

Conclusions:

Although PSA had not been introduced in the clinical practice at the start of the study, we were still able to show that it is possible to perform a long-term population-based randomised controlled study with standardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised. Complete data on stage, treatment and mortality for both groups was obtained from a validated cancer register, which is a fundamental prerequisite when assessing screening programmes.

Introduction

Prostate cancer is one of the most common forms of cancer in most western countries [1] and also a major cause of cancer death. However, despite the impact of prostate cancer on general health, little is known about how it can be prevented. The only way to provide definite evidence for improved survival from screening is by randomised controlled clinical trials. Such studies have been initiated in the United States [2] as well as in Europe [3], but will not provide data on mortality for several years. Performing a study aimed at showing mortality reduction after the introduction of a screening programme requires extremely large resources. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial of the National Cancer Institute in the US was planned on the assumption that 74,000 men had to be recruited to achieve sufficient power to show a reduction in prostate cancer mortality after ten years [2]. Furthermore, these studies must continue for a long period of time since prostate cancer progresses slowly. While awaiting the outcome of these studies, we have to rely on studies on smaller scale, addressing surrogate endpoints to obtain temporary evidence regarding the effectiveness of prostate cancer screening. A crucial requirement for all screening programmes is that the technique to be used effectively detects a latent or early symptomatic stage of the disease and that the tumour can be radically treated at this stage.

In order to see if a screening programme for prostate cancer is feasible we have performed a randomised controlled clinical trial, designed as a pilot study with one control group and one group of men randomised to screening every third year. The study was started 1987, before PSA was established as a method of screening [4]. At the first two screening sessions digital rectal examination was thus the sole method of screening. From 1993 this was combined with a PSA test. The screened group as well as the controls resided within the same geographic area, which was covered by a regional prostate cancer register. Since the register included data on tumour stage, tumour grade and cancer-specific mortality it was possible to detect differences in the extent of tumour growth and survival between the two groups. Results from the first screening session have previously been published [4], [5], [6]. Today 15 years have elapsed since the first screening session and we are now able to show the clinical consequences of screening in a population-based cohort of 9026 men aged 50–69 years in 1987.