| 21. |
- 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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| 22. |
- Siltanen, Sanna, et al.
(författare)
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ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer
- 2008
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 16:8, s. 983-91
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a nonsense alteration Trp149Stop in the ARLTS1 gene was found more frequently in familial cancer cases versus sporadic cancer patients and healthy controls. Here, the role of Trp149Stop or any other ARLTS1 germline variant was evaluated on breast, prostate, and colorectal cancer risk. The whole gene was screened for germline alterations in 855 familial cancer patients. The five observed variants were further screened in 1169 non-familial cancer patients as well as in 809 healthy population controls. The Trp149Stop was found at low frequencies (0.5-1.2%) in all patient subgroups versus 1.6% in controls, and the mutant allele did not co-segregate with disease status in families with multiple affected individuals. The CC genotype in the Cys148Arg variant was slightly more common among both familial and sporadic breast (odds ratio (OR), 1.48; 95% confidence interval (CI), 1.16-1.87; P=0.001) and prostate cancer patients (OR, 1.50; 95% CI, 1.13-1.99; P=0.005) when compared to controls. A novel ARLTS1 variant Gly65Val was found at higher frequency among familial prostate cancer patients (8 of 164, 4.9%) than in controls (13 of 809, 1.6%; OR, 3.14; 95% CI, 1.28-7.70, P=0.016). However, after adjusting for multiple testing, none of these results were still significant. No association was found with any of the variants and colorectal cancer risk. Our results suggest that Trp149Stop is not a predisposition allele in breast, prostate, or colorectal cancer in the Finnish population, and, while the Gly65Val variant may increase familial prostate cancer risk and the Cys148Arg change may affect both breast and prostate cancer risk, the evidence is not strong in these data.
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| 23. |
- Thomsen, Frederik B., et al.
(författare)
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Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer : Long-term follow-up of the SPCG-6 study
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 51:10, s. 1283-1292
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. Methods: A randomised, double-blind, parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to standard care in patients with hormone-naive, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). Findings: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6 years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p = 0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR) = 0.77 (95% confidence interval (CI): 0.63-0.94, p = 0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR = 1.19 (95% CI: 1.00-1.43), p = 0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28 ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n = 991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment. Interpretation: Throughout the 14.6 year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA. (C) 2015 Elsevier Ltd. All rights reserved.
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| 24. |
- Wolters, Tineke, et al.
(författare)
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The effect of study arm on prostate cancer treatment in the large screening trial ERSPC.
- 2010
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215. ; 126:10, s. 2387-93
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) mortality is the most valid end-point in screening trials, but could be influenced by the choice of initial treatment if treatment has an effect on mortality. In this study, PC treatment was compared between the screening and control arms in a screening trial. Data were collected from the European Randomized Study of Screening for Prostate Cancer (ERSPC). The characteristics and initial treatment of PC cases detected in the screening and the control arm were compared. Polytomous logistic regression analysis was used to assess the influence of study arm on treatment, adjusting for potential confounders and with statistical imputation of missing values. A total of 8,389 PC cases were detected, 5,422 in the screening arm and 3,145 in the control arm. Polytomous regression showed that trial arm was associated with treatment choice after correction for missing values, especially in men with high-risk PC. A control subject with high-risk PC was more likely than a screen subject to receive radiotherapy (OR: 1.43, 95% CI: 1.01-2.05, p = 0.047), expectant management (OR: 2.92, 95% CI: 1.33-6.42, p = 0.007) or hormonal treatment (OR: 1.77, 95% CI: 1.07-2.94, p = 0.026) instead of radical prostatectomy. However, trial arm had only a minor role in treatment choice compared to other variables. In conclusion, a small effect of trial arm on treatment choice was seen, particularly in men with high-risk PC. Therefore, differences in treatment between arms are unlikely to play a major role in the interpretation of the results of the ERSPC.
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| 25. |
- Ahlgren, Göran M., et al.
(författare)
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Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer : Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 73:6, s. 870-876
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer. Objective: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer. Design, setting, and participants: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. Inclusion criteria: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml. Intervention: Docetaxel treatment after prostatectomy. Results and limitations: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p = 0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint. Conclusions: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy. Patient summary: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy. In this randomised trial, docetaxel without hormonal therapy or continuous corticosteroids was given after radical prostatectomy for high-risk prostate cancer. We found no benefit from docetaxel alone given after radical prostatectomy.
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| 26. |
- Assel, Melissa, et al.
(författare)
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A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy : An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 5:4, s. 561-567
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Tidskriftsartikel (refereegranskat)abstract
- Background: A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4Kscore™. Objective: To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Design, setting, and participants: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls. Outcome measurements and statistical analysis: The predictive accuracy of prespecified prediction models was compared with biopsy outcomes. Results and limitations: Among men with PSA of 4.0-25. ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614-0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717-0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p = 0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0-3.99. ng/ml and the absence of digital rectal examination results. Conclusions: These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. Patient summary: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen. Four kallikrein markers and β-microseminoprotein (MSP) in blood improve discrimination of high-grade cancer at biopsy in men with elevated prostate-specific antigen. These kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP.
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| 27. |
- Auvinen, Anssi, et al.
(författare)
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Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI : The ProScreen Randomized Trial
- 2024
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Ingår i: JAMA. - 0098-7484. ; 331:17, s. 1452-1459
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important.OBJECTIVE: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan.DESIGN, SETTING, AND PARTICIPANTS: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020.INTERVENTIONS: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023.MAIN OUTCOMES AND MEASURES: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group.RESULTS: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer.CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03423303.
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| 28. |
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| 29. |
- Hahn, Robert G., et al.
(författare)
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Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride
- 2007
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Ingår i: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 99:3, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether pretreatment with dutasteride, a dual 5alpha-reductase inhibitor (5ARI), reduces surgical blood loss or postoperative complications in patients with benign prostatic hyperplasia (BPH) who undergo transurethral resection of the prostate (TURP).PATIENTS AND METHODS: This double-blind, randomized, placebo-controlled, multicentre study comprised 214 patients with BPH. Placebo was compared with dutasteride 0.5 mg/day 2 weeks before and after TURP, or 4 weeks before and 2 weeks after TURP. Surgical blood loss was measured using a haemoglobin photometer (HemoCue AB, Angelholm, Sweden) and postoperative adverse events were recorded. Microvessel density (MVD) was calculated by immunostaining and light microscopy of the prostatic chips.RESULTS: Although dutasteride reduced serum dihydrotestosterone (DHT) by 86-89% in 2-4 weeks, and intraprostatic DHT was approximately 10 times lower than in the placebo group, the (adjusted) mean haemoglobin (Hb) loss during surgery was 2.15-2.55 g Hb/g resectate with no significant difference in blood loss between the groups either during or after TURP. Clot retention occurred in 6-11% and urinary incontinence in 14-15% of patients during the 14 weeks after TURP, with no difference between the groups. The MVD at TURP was also similar for all groups.CONCLUSION: There were no significant reductions in blood loss during or after TURP or complications afterward with dutasteride compared with placebo, despite significant suppression of intraprostatic DHT. Blood loss and transfusion rates in the placebo group were lower than those previously reported in studies where there was a beneficial effect of a 5ARI, relative to placebo, on bleeding during TURP.
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| 30. |
- Iversen, Peter, et al.
(författare)
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Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer : updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years
- 2006
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Ingår i: Scandinavian Journal of Urology and Nephrology. - London : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 40:6, s. 441-452
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.
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