br A screening trial Stockholm invited
A screening trial (Stockholm, 1988–1989) invited 2400 men aged 55–70 yr only once and found no difference in PCa mortality after 20 yr from a nonscreened source population; however, statistical power was limited . Similar results were observed in the present study: men aged 70–74 yr were invited only once, and in this age group, no effect on PCa mortality was seen (Supplementary Table 1). No PCa mortality reduction was shown after 15 yr in the US PLCO trial, which applied only 6 yr of screening . Despite several other components of this study may explain the PLCO null result, including large control group contamination, the short screening STA-21 may have contributed [23,24]. Within ERSPC, Finland showed only a
small mortality reduction (RR 0.91) compared with the Netherlands (RR 0.67) and Sweden (RR 0.63). In Finland, the oldest age group where a quarter of the men were invited only twice, the mean number of screening visits was 1.6. In the Netherlands, all men in the core age group were invited at least three times and the youngest up to five times, with on average 2.3 screening visits. In Sweden, all men were also invited at least three times and the youngest eight times, with on average 2.6 screening visits. The[23$DIF] results[24T$DIF] from these three larger centres in ERSPC with different screening intensity indicate[25T$DIF] that the length and intensity of screening are directly correlated to mortality reduction (Table 1). The recently published CAP study invited 189 386 cluster-randomised men to one-time screening, of whom 40% participated. They found no significant effect on PCa mortality (RR 0.96, CI 0.85–1.08; average follow-up 10 yr) . The data encouraged us to analyse the effect of repeated screening rounds assuming various effects from one test only (Supplementary Table 4). Men attending at least one screening round had, after correction for nonattendance, a PCa mortality reduction of 25%, and those who attended at least two screening rounds had a decrease of 48% assuming no effect of one-time screening. This model may explain the large differences in PCa mortality reduction observed between the centres within ERSPC, but other explanations may also contribute, for example, the rate of opportunistic screening in the control group (eg, Finland) . This report shows that cancers detected in round 1 have a poorer prognosis, but this is partly due to the ERSPC study design where men started screening in various age cohorts with a median age of 60 yr at randomisation. Older men screened for the first time showed a higher risk of being diagnosed with incurable disease . In a running screening programme, men are invited from earlier age (50–55 yr), and the risk of missing the “window of cure” is probably lower. Furthermore, randomised screening trials will underestimate the true effect of an effective population-based screening programme .
Our study has limitations including heterogeneous populations with different background risks between centres, possibly influencing the results. Another limitation is the increased uptake of opportunistic screening in Europe, which could underestimate the true effects of screening.
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 contributions: Jonas Hugosson had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.