Study Results

Published Study Results

New publications

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer. Kinnunen PTT, Murtola TJ, Talala K, Taari K, Tammela TLJ, Auvinen A. BMC Cancer. 2017 Aug 29;17(1):585.
Summary: In the study population 6,537 men were diagnosed with prostate cancer (PCa) and 728 died from PCa. We compared risk of PCa death between warfarin users and 1) men using other anticoagulants and 2) anticoagulants non-users. Risk of PCa death between warfarin users and users of other anticoagulants was similar. Overall use of warfarin was associated with increased of PCa death compared to anticoagulant non-users (HR 1.47 95% CI 1.13-1.93). Increased risk was limited to low-dose, low-intensity use of warfarin. Otherwise no risk difference was found. Increased risk of PCa death associated with low-dose use of warfarin is likely due to higher risk of thrombotic events in terminal PCa.

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.
Summary:  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.

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.
Summary: 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.

Estimate of opportunistic prostate-specific antigen testing in the Finnish Randomized Study of Screening for Prostate Cancer. Kilpeläinen T, Pogodin-Hannolainen D, Kemppainen K, Talala K, Raitanen J, Taari K, Kujala P, Tammela TLJ, Auvinen A. 2017.
Summary: The purpose of this study was to estimate the degree of opportunistic prostate-specific antigen testing in the control arm (CA) of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Our findings demonstrate considerable frequency of non-organized PSA testing (i.e. contamination) in the CA of the FinRSPC. Approximately 1.4% of men had been tested with PSA 1-3 years before randomization. By the first four, eight and twelve years of follow-up, 18.1%, 47.7% and 62.7% of the men in the CA had been tested with PSA at least once, respectively. In the screening arm (SA), the corresponding proportions were 69.8%, 81.1% and 85.2%.

Published Study Results

Greater absolute benefit from PSA screening at 13 years of follow-up in the ERSPC trial not sufficient to justify population-based screening

The third analysis on prostate cancer mortality in the ERSPC trial, published in the Lancet August 2014, shows stable relative (RR=0.79) but larger absolute benefit in follow-up extended to 13 years (two additional years from the previous report).

The ERSPC is the largest randomized trial of screening for prostate cancer with 162,388 men and 900 prostate cancer deaths. Screening is based on regular prostate-specific antigen (PSA) testing every 2-4 years in the intervention arm and usual care with no screening offered in the control arm. The ERSPC trial has previously demonstrated significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up of our trial (Schröder and colleagues publications in the New England Journal of Medicine 2009 and 2012). We now provide updated results truncated at 13 years for men in the core age group of the study, aged 55-69 years at randomization.

In this update of the ERSPC with follow-up truncated at 13 years, a significant 21% relative reduction in prostate cancer was found in intention to screen analyses, and 27% in men who actually attended screening. The absolute risk reduction of death from prostate cancer at 13 years, with 1.28 fewer prostate cancer deaths per 1,000 men randomized was increased by a quarter compared with analyses limited to 11 years. A total of 781 men needed to be invited to screening (“NNI”=number needed to invite) and 27 to be diagnosed (“NND”=number needed to diagnose) with prostate cancer to avert one death from the disease. These numbers are substantially lower compared to previous reports at 9 years (NNI 1410, NND 48) and 11 years (NNI 979, NND 35) demonstrating a larger effect.

The main drawback of screening is the increased risk of overdiagnosis of prostate cancer due to screening, meaning detection of cancers that may not give rise to symptoms or lead to death during the lifetime of a typical man.

Despite showing a clear prostate cancer mortality reduction, the findings are not sufficient to justify population-based screening. We still need further quantification of harms of screening and better strategies to overcome overdiagnosis and overtreatment for both more targeted screening and assessment of prostate cancer risk, such as multivariate risk stratification. In the meantime, well-informed men suitable for screening should have access to PSA-testing if they wish after careful consideration of the pros and cons. Various decision support tools are available online developed for communication of the pros and cons for men considering screening to discuss with their doctors. Multiparametric magnetic resonance imaging holds promise in evaluation of screen-positive men and is being tested in large scale trials.

Published Study Results

Latest findings confirm increased mortality benefit from prostate cancer testing

The European Randomized Study of Screening for Prostate Cancer has published its 11-year follow-up results (New England Journal of Medicine, March 15 2012). Once again, they demonstrate that screening does significantly reduce death from prostate cancer. The latest study confirms that a man who undergoes PSA testing will have his risk of dying from prostate cancer reduced by 29%.

Extended follow up will assess full impact of screening

By increasing follow-up to an average of 11 years, the ERSPC has shown that 31% fewer men than previously indicated would need to be diagnosed with cancer to save one life. So far, only about 30% of all men in the study have died.

If a larger reduction of prostate cancer mortality is seen by further extending the study beyond the current average of 11 years, the ERSPC can determine with greater certainty whether the benefit of screening outweighs the disadvantages.

ERSPC is the world’s largest randomized prostate cancer screening study. It was designed to investigate whether early detection and treatment of prostate cancer might reduce disease-specific mortality and also help to identify men at risk. From 1992, the ERSPC study randomized 162,000 men, aged 55 to 69, across Europe to either a screening arm or a control group. Those screened were given a blood test to detect PSA levels: if it was 3.0ng/ml or more, they were offered a biopsy. Screening took place on average every four years. Mean follow-up was 11 years. more»

This study is fundamentally different from the US-based Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial where at least 44% of participants in the control arm were already PSA-tested prior to being randomized into the study. The PLCO study has been unable to demonstrate any difference in prostate cancer mortality between the two arms of the study.

Original participating countries and details on specific protocols within each country: Belgium, Finland, France, Italy, Netherlands Spain, Sweden and Switzerland.