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- Carlsson, Sigrid, 1982, et al.
(författare)
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Could Differences in Treatment Between Trial Arms Explain the Reduction in Prostate Cancer Mortality in the European Randomized Study of Screening for Prostate Cancer?
- 2019
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 75:6, s. 1015-1022
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Tidskriftsartikel (refereegranskat)abstract
- Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC).To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA).A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55-69yr) at 16yr of follow-up.The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths.The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from -3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] -0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar-0.01% (95% CI -0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available.Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms.This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.
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- Carlsson, Sigrid, 1982, et al.
(författare)
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No excess mortality after prostate biopsy: results from the European Randomized Study of Screening for Prostate Cancer.
- 2011
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Ingår i: BJU international. - 1464-410X. ; 107:12, s. 1912-1917
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Tidskriftsartikel (refereegranskat)abstract
- Study Type - Harm (RCT)Level of Evidence1b OBJECTIVES: To assess possible excess mortality associated with prostate biopsy among screening participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC). SUBJECTS AND METHODS: From three centres in the ERSPC (Finland, The Netherlands and Sweden) 50194 screened men aged 50.2-78.4 years were prospectively followed. A cohort of 12959 first-time screening-positive men (i.e. with biopsy indication) was compared with another cohort of 37235 first-time screening-negative men. Overall mortality rates (i.e. other cause than prostate cancer mortality) were calculated and the 120-day and 1-year cumulative mortality were calculated by the Kaplan-Meier method, with a log-rank test for statistical significance. Incidence rate ratios (RR) and statistical significance were evaluated using Poisson regression analyses, adjusting for age, total PSA level, screening centre and whether a biopsy indication was present, or whether a biopsy was actually performed or not. RESULTS: There was no statistically significant difference in cumulative 120-day other cause mortality between the two groups of men: 0.24% (95% CI, 0.17-0.34) for screening-positive men vs 0.24% (95% CI, 0.20-0.30) for screening-negative men (P= 0.96). This implied no excess mortality for screening-positive men. Screening-positive men who were not biopsied (n= 1238) had a more than fourfold risk of other cause mortality during the first 120 days compared to screening-negative men: RR, 4.52 (95% CI, 2.63-7.74) (P < 0.001), adjusted for age, whereas men who were actually biopsied (n= 11721) had half the risk: RR, 0.41 (95% CI, 0.23-0.73) (P= 0.002), adjusted for age. Only 14/31 (45%) of the screening-positive men who died within 120 days were biopsied and none died as an obvious complication to the biopsy. CONCLUSIONS: Prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare.
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- Carlsson, Sigrid V., et al.
(författare)
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Estimating the harms and benefits of prostate cancer screening as used in common practice versus recommended good practice : A microsimulation screening analysis
- 2016
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 122:21, s. 3386-3393
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific antigen (PSA) screening and concomitant treatment can be implemented in several ways. The authors investigated how the net benefit of PSA screening varies between common practice versus “good practice.”. METHODS: Microsimulation screening analysis (MISCAN) was used to evaluate the effect on quality-adjusted life-years (QALYs) if 4 recommendations were followed: limited screening in older men, selective biopsy in men with elevated PSA, active surveillance for low-risk tumors, and treatment preferentially delivered at high-volume centers. Outcomes were compared with a base model in which annual screening started at ages 55 to 69 years and were simulated using data from the European Randomized Study of Screening for Prostate Cancer. RESULTS: In terms of QALYs gained compared with no screening, for 1000 screened men who were followed over their lifetime, recommended good practice led to 73 life-years (LYs) and 74 QALYs gained compared with 73 LYs and 56 QALYs for the base model. In contrast, common practice led to 78 LYs gained but only 19 QALYs gained, for a greater than 75% relative reduction in QALYs gained from unadjusted LYs gained. The poor outcomes for common practice were influenced predominantly by the use of aggressive treatment for men with low-risk disease, and PSA testing in older men also strongly reduced potential QALY gains. CONCLUSIONS: Commonly used PSA screening and treatment practices are associated with little net benefit. Following a few straightforward clinical recommendations, particularly greater use of active surveillance for low-risk disease and reducing screening in older men, would lead to an almost 4-fold increase in the net benefit of prostate cancer screening. Cancer 2016;122:3386–3393.
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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 8. |
- Heijnsdijk, Eveline A M, et al.
(författare)
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Quality-of-life effects of prostate-specific antigen screening.
- 2012
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Ingår i: The New England journal of medicine. - 1533-4406. ; 367:7, s. 595-605
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Tidskriftsartikel (refereegranskat)abstract
- After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain.
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- Pasanen, Niko, et al.
(författare)
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Which men benefit from prostate cancer screening? Prostate cancer mortality by subgroup in the European Randomised Study of Screening for Prostate Cancer
- 2024
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Ingår i: BJU INTERNATIONAL. - 1464-4096 .- 1464-410X. ; 134:2, s. 291-299
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate whether a subgroup of men can be identified that would benefit more from screening than others.Materials and MethodsThis retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease.ResultsThe hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden.ConclusionWe were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift.
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- Roobol, Monique J., et al.
(författare)
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Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:4, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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