Impact of Prostatic-specific Antigen Threshold and Screening Interval in Prostate Cancer Screening Outcomes: Comparing the Swedish and Finnish European Randomised Study of Screening for Prostate Cancer Centres

Abstract

Background: The European Randomised Study of Screening for Prostate Cancer trial has shown a 21% reduction in prostate cancer (PC) mortality with prostate-specific antigen (PSA)-based screening. Sweden used a 2-yr screening interval and showed a larger mortality reduction than Finland with a 4-yr interval and higher PSA cut-off.

Objective: To evaluate the impact of screening interval and PSA cut-off on PC detection and mortality.

Design, setting, and participants: We analysed the core age groups (55-69 yr at entry) of the Finnish (N=31 866) and Swedish (N=5901) screening arms at 13 yr and 16 yr of follow-up. Sweden used a screening interval of 2 yr and a PSA cut-off of 3.0ng/ml, while in Finland the screening interval was 4 yr and the PSA cut-off 4.0ng/ml (or PSA 3.0-3.9ng/ml with free PSA<16%).

Outcome measurements and statistical analysis: We compared PC detection rate and PC mortality between the Finnish and Swedish centres and estimated the impact of different screening protocols.

Results and limitations: If the Swedish screening protocol had been followed in Finland, 122 additional PC cases would have been diagnosed at screening, 84% of which would have been low-risk cancers, and four leading to PC death. In contrast, if a lower PSA threshold had been applied in Finland, at least 127 additional PC would have been found, with 19 PC deaths.

Conclusions: The small number of deaths among cases that would have been potentially detectable in Finland with the Swedish protocol (or those that would have been missed in Sweden with the Finnish approach) is unlikely to explain the differences in mortality in this long of a follow-up.

Patient summary: A prostate-specific antigen threshold of 3ng/ml versus 4ng/ml or a screening interval of 2 yr instead of 4 yr is unlikely to explain the larger mortality reduction achieved in Sweden compared with Finland.

Keywords: Prostate cancer; Prostate-specific antigen; Randomised trials; Screening.

Figure 1

A Consort Style Flow Chart from Finnish Screening Arm

Figure 2

A Consort Style Flow Chart from Finnish Screening Arm

Figure 3

Kaplan-Meier Survival Curve showing prostate cancer survival for all men in SA. No difference was shown in prostate cancer survival between Finnish and Swedish screening arms as hazard ratio was 0.88 (CI 95% 0.67–1.15)

Figure 4

Kaplan-Meier Survival Curve showing the prostate cancer survival for men with PSA first time between 3–4 (free/total PSA not taken into account). No difference was observed as hazard ratio was 0.75 (95% CI 0.33–1.63). Although the number of events is low in both groups this suggest that if PSA is 3–4 ng/ml in PC screening, it does not matter whether to refer the men to further work-up or not