Surgeon volume and patient-reported urinary incontinence after radical prostatectomy : Population-based register study in Sweden

Objective To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. Methods A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: 'How much urine leakage do you experience?' with the response alternatives 'Not at all', 'A little', defined as continence and 'Moderately', 'Much/Very much' as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. Results 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48-3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04-1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26-1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. Conclusions The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results

Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy : Nationwide, population-based study

Background and objective: Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group. Methods: 9,810 RARP's registered in the National Prostate Cancer Register of Sweden (2015-2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection. Results: Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11-11.91), hospital (OR 2.16, 95% CI 1.53-3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07-3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34-3.57), hospital (OR 2.02, 95% CI 1.66-2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54-2.35), hospital (OR 1.28, 95% CI 1.07-1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment. Conclusions: High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement

The Study of Active Monitoring in Sweden (SAMS): A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer.

Abstract Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10--15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule

Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer

Introduction Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. Methods Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. Results Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa. Conclusion SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.Funding Agencies|Jonko ping Clinical Cancer Research Foundation [110426-1]; Futurum the Academy for health and care [144631]; Medical Research Council of Southeast Sweden (FORSS) [567001]; Internal research Laboratory Medicine; Swedish Match AB</p

COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial

Objectives: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. Trial design: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. Participants: Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. Intervention and comparator: Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. Main outcomes: The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). Randomisation: Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) Blinding (masking): This is an open-label trial. Numbers to be randomised (sample size): The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. Trial Status: The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. Trial registrationEudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020 Full protoco: lThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

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

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