Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Haring A, Murtola TJ, Talala K, Taari K, Tammela TL, Auvinen A. Scand J Urol. 2017 Jan 13:1-11.
Diabetic men have lowered overall prostate cancer (PCa) risk, while their risk of high-grade disease may be elevated. The antidiabetic drug metformin may reduce the risk. This study evaluated PCa incidence among users of metformin and other antidiabetic drugs in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Among antidiabetic drug users, metformin lowered the overall PCa risk, while the risk of metastatic disease was elevated in sulphonylurea users. As sulphonylureas stimulate insulin secretion, the results suggest that hyperinsulinemia may be a risk factor for PCa.
What explains the differences between centres in the European screening trial? A simulation study. Nevalainen J, Stenman U-H, Hugosson J, Tammela T, Roobol M, Carlsson S, Talala K, Schröder FH, Auvinen A. Cancer Epidemiol. 2016 Nov 24;46:14-19.
The ERSPC has shown a significant 21% reduction in PrCa mortality at 13 years of follow-up. The effect of screening appears to vary across centres, for which several explanations are possible. We set to assess if the apparent differences in PrCa mortality reduction between the centres can be explained by differences in screening protocols. We examined the centre differences by developing a simulation model and estimated how alternative screening protocols would have affected PrCa mortality. Our results showed outcomes similar to those observed, when the results by centres were reproduced by simulating the screening regimens with PSA threshold of 3 versus 4 ng/ml, or screening interval of two versus four years. The findings suggest that the differences are only marginally attributable to the different screening protocols. The small screening impact in Finland was not explained by the differences in the screening protocols. A possible reason for it was the contamination of and the unexpectedly low PrCa mortality in the Finnish control arm.
Impact of cause of death adjudication on the results of the European prostate cancer screening trial. Walter SD, de Koning HJ, Hugosson J, Talala K, Roobol MJ, Carlsson S, Zappa M, Nelen V, Kwiatkowski M, Páez Á, Moss S, Auvinen A; ERSPC Cause of Death Committees. Br J Cancer. 2017 Jan 3;116(1):141-148.
The European Randomised Study of Prostate Cancer Screening has shown a 21% relative reduction in prostate cancer mortality at 13 years. The causes of death can be misattributed, particularly in elderly men with multiple comorbidities, and therefore accurate assessment of the underlying cause of death is crucial for valid results. To address potential unreliability of endpoint assessment, and its possible impact on mortality results, we analysed the study outcome adjudication data in six countries. Latent class statistical models were formulated to compare the accuracy of individual adjudicators, and to assess whether accuracy differed between the trial arms. We used the model to assess whether correcting for adjudication inaccuracies might modify the study results. There was some heterogeneity in adjudication accuracy of causes of death, but no consistent differential accuracy by trial arm. Correcting the estimated screening effect for misclassification did not alter the estimated mortality effect of screening. A bias in assigning causes of death that might have explained the mortality reduction by screening can be effectively ruled out.