Summary: We combined data from 20 years of the Finnish Randomised study of Screening for Prostate Cancer (FinRSPC) with information on costs and effectiveness from national registries. In addition to examining cost-effectiveness in terms of overall mortality, we also examined it in terms of diagnosed men’s mortality from prostate cancer and mortality with, but not from, prostate cancer. Although we found that mass screening likely helps to avert just over one prostate-cancer death per 1000 men screened, we also found five additional non-prostate-cancer deaths among diagnosed men, per 1000 men screened. These findings should be corroborated or contradicted by similar analyses using data from other trials, in order to reveal if more diagnosed men have also died elsewhere.
Lindberg A, Talala K, Kujala P, Stenman U-H, Taari K, Kilpeläinen TP, Tammela T, Auvinen A. Bias-corrected estimates of PSA screening decisions on the risk of prostate cancer diagnosis and death: Analysis of the Finnish Randomized Study of Screening for Prostate Cancer. Int J Cancer Jan 2019 doi:10.1002/ijc.32129
We used a counterfactual exclusion method on the data of the FinRSPC to adjust for the effects of screening non-compliance and PSA contamination on risk of PC incidence and PC death at 15 years of follow-up. After correcting for non-compliance and contamination, PSA screening led to 32.4 (95% CI 26.4, 38.6) more PC diagnoses per 1,000 men and 1.4 (95% CI 0.0, 2.8) fewer PC deaths compared to the control arm. These results can be used for patient counselling in informed decision-making about PC screening. Because the previous studies have mainly concentrated on the population-level effects of screening, our study offers new and topical results relevant for clinical practice.
Kukko V, Kaipia A, Talala K, Taari K, Tammela TLJ, Auvinen A, Murtola TJ. Allopurinol and risk of prostate cancer in a Finnish population-based cohort. Prostate Cancer and Prostatic Diseases 2019 Jan 29. doi: 10.1038/s41391-019-0129-2.
We studied the association between allopurinol use and prostate cancer (PCa) incidence. The cohort consists of 76,874 men without prevalent PCa, originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). We used Cox regression (adjusted for age, FinRSPC trial arm, PCa family history and use of other medication) to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of PCa risk by allopurinol use. There were 9,062 new PCa diagnoses in the cohort. The risk of PCa did not differ by allopurinol use (multivariable adjusted HR 1.03; 95% CI 0.92-1.16).
Murtola TJ, Vihervuori VJ, Lahtela J, Talala K, Taari K, Tammela TL, Auvinen A. Fasting blood glucose, glycemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Br J Cancer. 2018 May;118(9):1248-1254
Summary: Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycemia is unclear. In this cohort study we estimated PCa risk among men with diabetic fasting blood glucose level. Based on the average yearly level men were categorized as normoglycemic, prediabetic or diabetic. Compared to normoglycemic men, men with diabetic blood glucose level had increased risk of PCa. The risk increase was observed for all tumor grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association.
Booth N, Rissanen P, Tammela TLJ, Taari K, Talala K, Auvinen A. Register-based healthcare cost estimates during the first 20 years of the Finnish Randomised study of Screening for Prostate Cancer. Eur J Cancer. 2018 Apr;93:108-118.
Summary: We estimate differences in register-based costs of publicly-funded healthcare in each arm of the Finnish Randomised study of Screening for Prostate Cancer (FinRSPC) after 20 years. For all men diagnosed with PCa during the 20-year observation period, PCa-related costs appeared to be less than 10% lower in the screening arm (SA) on average: 14,200 euros in the SA versus 15,300 euros in the control arm (CA). All-cause healthcare costs for these men were also lower in the SA on average, but differences were smaller than for PCa-related costs alone, and no longer statistically significant. For men dying from PCa, although the difference was not statistically significant, all-cause healthcare costs were around 10% higher on average: 65,100 euros in the SA versus 60,000 euros in the CA. Despite long-term follow-up of the FinRSPC cohort, the 20-year period is too short to provide definitive information about screening’s impact on healthcare costs.
Murtola TJ, Kasurinen TVJ, Talala K, Taari K, Tammela TLJ, Auvinen A. Serum cholesterol and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Accepted Prostate Cancer and Prostatic Diseases May 2018.
Summary: We examined PCa risk by lipid parameters in a population nested within the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Cholesterol measurements were available for 17,696 men over 17-year median follow-up. Higher total cholesterol (TC) and LDL levels were associated with increased risk of Gleason 8-10 PCa. Overall PCa risk was elevated in men with higher TC and HDL with 3 years’ time lag. However, inverse risk association was seen with 20 years’ lag time for TC.
Kaapu K J, Talala K, Taari K, Tammela TLJ, Auvinen A, Murtola TJ. Cancer mortality by antiarrhythmic drug use in a population-based cohort of Finnish men. Nature Scientific Reports 2018:8:10308 |
Summary: We evaluated the association between cancer mortality and antiarrhythmic drug use among men participating in the Finnish Randomized Study of Screening for Prostate Cancer. Cancer mortality was increased among any antiarrhythmic drug users, digoxin users and sotalol users when compared to non-users. However, the risk associations disappeared in long-term use and were modified by background co-morbidities and thus the association is likely non-causal.
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.
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.