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- Welén, Karin, 1970, et al.
(författare)
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A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
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Tidskriftsartikel (refereegranskat)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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| 4. |
- Forsmark, A., et al.
(författare)
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Health Economic Analysis of Open and Robot-assisted Laparoscopic Surgery for Prostate Cancer Within the Prospective Multicentre LAPPRO Trial
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 74:6, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rapid adoption of robot-assisted laparoscopy in radical prostatectomy has preceded data regarding associated costs. Qualitative evidence regarding cost outcomes is lacking. Objective: This study assessed how costs were affected by robot-assisted laparoscopic prostatectomy (RALP) compared with open surgery. Design, setting, and participants: Cost analysis was based on the dataset of the LAPPRO (Laparoscopic Prostatectomy Robot Open) clinical trial, which is a prospective controlled, nonrandomised trial of patients who underwent prostatectomy at 14 centres in Sweden between September 2008 and November 2011. Currently, data are available from a follow-up period of 24 mo. Intervention: In the LAPPRO trial, RALP was compared with radical retropubic prostatectomy (RRP). Outcome measurements and statistical analysis: Costs per surgical technique were assessed based on resource variable data from the LAPPRO database. The calculation of average costs was based on mean values; Swedish currency was converted to purchasing power parity US dollar (PPP$). All tests were two-tailed and conducted at alpha = 0.05 significance level. Results and limitations: The cost analysis comprised 2638 men. Based on the LAPPRO trial data, RALP was associated with an increased cost/procedure of PPP$ 3837 (95% confidence interval: 2747-4928) compared with RRP. The result was sensitive to variations in caseload. Main drivers of overall cost were robotic system cost, operation time, length of stay, and sick leave. Limitations of the study include the uneven distribution between RALP and RRP regarding procedures in public/for-profit hospitals and surgeon/centre procedural volume. Conclusions: Based on the LAPPRO trial data, this study showed that RALP was associated with an increased cost compared with RRP in Swedish health care. There are many factors influencing the costs, making the absolute result dependent on the specific setting. However, by identifying the main cost drivers and/or most influential parameters, the study provides support for informed decisions and predictions. Patient summary: In this study, we looked at the cost outcome when performing prostatectomies by robot-assisted laparoscopic technique compared with open surgery in Sweden. We found that the robot-assisted procedure was associated with a higher mean cost. (C) 2018 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.
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| 6. |
- Jochems, Sylvia H J, et al.
(författare)
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Smoking and risk of prostate cancer and prostate cancer death : a pooled study
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:5, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospective and detailed investigations of smoking and prostate cancer (PCa) risk and death are lacking.Objective: To investigate prediagnosis smoking habit (status, intensity, duration, and cessation) as a risk factor, on its own and combined with body mass index (BMI), for PCa incidence and death.Design, setting, and participants: We included 351 448 men with smoking information from five Swedish cohorts. Outcome measurements and statistical analysis: We used Cox regression to calculate hazard ratios (HRs) and confidence intervals (CIs) for PCa incidence (n = 24 731) and death (n = 4322).Results and limitations: Smoking was associated with a lower risk of any PCa (HR 0.89, 95% CI 0.86–0.92), which was most pronounced for low-risk PCa (HR 0.74, 95% CI 0.69–0.79) and was restricted to PCa cases diagnosed in the prostate-specific antigen (PSA) era. Smoking was associated with a higher risk of PCa death in the full cohort (HR 1.10, 95% CI 1.02–1.18) and in case-only analysis adjusted for clinical characteristics (HR 1.20, 95% CI 1.11–1.31), which was a consistent finding across case groups (p = 0.8 for heterogeneity). Associations by smoking intensity and, to lesser degree, smoking duration and cessation, supported the associations for smoking status. Smoking in combination with obesity (BMI ≥30 kg/m2) further decreased the risk of low-risk PCa incidence (HR 0.40, 95% CI 0.30–0.53 compared to never smokers with BMI <25 kg/m2) and further increased the risk of PCa death (HR 1.49, 95% CI 1.21–1.84). A limitation of the study is that only a subgroup of men had information on smoking habit around the time of their PCa diagnosis.Conclusions: The lower PCa risk for smokers in the PSA era, particularly for low-risk PCa, can probably be attributed to low uptake of PSA testing by smokers. Poor survival for smokers, particularly obese smokers, requires further study to clarify the underlying causes and the preventive potential of smoking intervention for PCa death.Patient summary: Smokers have a higher risk of dying from prostate cancer, which further increases with obesity.
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- Josefsson, Andreas, 1979-, et al.
(författare)
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Performance of 4Kscore as a Reflex Test to Prostate-specific Antigen in the GÖTEBORG-2 Prostate Cancer Screening Trial
- 2024
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560.
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC). Methods: In the GÖTEBORG-2 PC screening trial, 38 000men (50–60 yr) were invited to PSA testing and, if elevated, followed by magnetic resonance imaging (MRI). For 571 men with PSA ≥3.0 ng/ml and evaluable outcomes, 4Kscore was calculated. The performance using a prespecified 4Kscore cutoff of 7.5% was evaluated. Key findings and limitations: The area under the curve for 4Kscore to identify intermediate- and high-risk PC was 0.84 (95% confidence interval 0.79–0.89), and the positive predictive value, and negative predictive value were 15% (0.12–0.20) and 99% (97–100%), respectively. Of the 54 men diagnosed with intermediate- or high-grade PC, two had a 4Kscore cutoff below 7.5%, both with organ-confined intermediate-risk PC. Per 1000 men with elevated PSA, adding 4Kscore would have resulted in avoidance of MRI for 408 (41%) men, biopsies for 95 (28% reduction) men, and diagnosis of 23 low-grade cancers (23% reduction) while delaying the diagnosis of four men with intermediate-grade cancers (4%). Conclusions and clinical implications: Including 4Kscore as a reflex test for men with elevated PSA reduces the need for MRI and biopsy markedly, and results in less overdiagnosis of low-grade PC at the cost of delaying the diagnosis of intermediate-grade PC in a few men. These results add further evidence for including new blood-based biomarkers in addition to PSA to improve the harm and benefit ratio of PC screening and reduce the need for resource-demanding MRI and biopsies. Patient summary: In this study, 4Kscore, a blood-based biomarker, as a reflex test for men with elevated prostate-specific antigen (PSA), reduces the need for magnetic resonance imaging and biopsy. These results support the inclusion of new blood-based biomarkers in addition to PSA.
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| 8. |
- Li, Weiqiang, et al.
(författare)
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Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 74:6, s. 710-719
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Tidskriftsartikel (refereegranskat)abstract
- We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence.
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| 9. |
- Sooriakumaran, Prasanna, et al.
(författare)
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Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy : Results from the LAParoscopic Prostatectomy Robot Open Trial
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 73:4, s. 618-627
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. Objective: To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. Design, setting, and participants: In a prospective nonrandomised trial, we recruited 2545 men with prostate cancer from seven open (n = 753) and seven robot-assisted (n = 1792) Swedish centres (2008-2011). Outcome measurements and statistical analysis: Clinometrically-validated questionnaire-based patient-reported erectile function was collected before, 3 mo, 12 mo, and 24 mo after surgery. Surgeon-reported degree of neurovascular-bundle preservation, pathologist-reported positive surgical margin (PSM) rates, and 2-yr prostate-specific antigen-relapse rates were measured. Results and limitations: Among 1702 preoperatively potent men, we found enhanced erectile function recovery for low/intermediate-risk patients in the robot-assisted group at 3 mo. For patients with high-risk tumours, point estimates for erectile function recovery at 24 mo favoured the open surgery group. The degree of neurovascular bundle preservation and erectile function recovery were greater correlated for robot-assisted surgery. In pT2 tumours, 10% versus 17% PSM rates were observed for open and robot-assisted surgery, respectively; corresponding rates for pT3 tumours were 48% and 33%. These differences were associated with biochemical recurrence in pT3 but not pT2 disease. The study is limited by its nonrandomised design and relatively short follow-up. Conclusions: Earlier recovery of erectile function in the robot-assisted surgery group in lower-risk patients is counterbalanced by lower PSM rates for open surgeons in organ-confined disease; thus, both open and robotic surgeons need to consider this trade-off when determining the plane of surgical dissection. Robot-assisted surgery also facilitates easier identification of nerve preservation planes during radical prostatectomy as well as wider dissection for pT3 cases. Patient summary: For prostate cancer surgery, an open operation reduces erection problems in high-risk cancers but has higher relapse rates than robotic surgery. Relapse rates appear similar in low/intermediate-risk cancers and the robot appears better at preserving erections in these cases. Robot-assisted surgery appears to improve erectile function recovery compared with open radical prostatectomy for low- and intermediate-risk tumours, whereas the opposite is true for high-risk disease. Margin and recurrence rates are worse for open surgical patients with pT3 disease.
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