Data Availability Statements and Data Sharing in Urology: A False Promise?

BACKGROUND AND OBJECTIVE: It is considered standard for authors of scientific papers to provide access to their raw data. The purpose of this study was to investigate data availability statements (DAS) and the actual availability of data in urology. METHODS: The DAS policies of the top ten urology journals were retrieved. Then 190 selected papers were classified according to their DAS status. Finally, we contacted the corresponding authors of papers that stated that data were available on request to enquire about this possibility. KEY FINDINGS AND LIMITATIONS: All journals either required or highly recommended a DAS. Among the selected articles, 52% (99/190) included a DAS stating data availability, most often on reasonable request to the corresponding author. A formal DAS was lacking in 29.5% (56/190) of the articles, with an additional 18.3% (35/190) citing various reasons for data unavailability. On contact, 23.4% (15/64) of corresponding authors indicated a willingness to share their data. Overall, data were unavailable in 73.7% (140/190) of cases. There was no difference between papers dealing with malignant and benign diseases. CONCLUSIONS AND CLINICAL IMPLICATIONS: There is a gap between the intention to share data and actual practice in major urological journals. As data sharing plays a critical role in safeguarding the reliability of published results and in the potential for reanalysis and merging of datasets, there is a clear need for improvement. Easier access to data repositories and stronger enforcement of existing journal policies are essential. PATIENT SUMMARY: To ensure the reliability of data and allow further analyses, major urology journals require authors to make their data available to other researchers when possible. However, in practice we found that data were only accessible for about a quarter of published scientific papers.

Beneficial effects of exercise, testosterone, vitamin D, calcium and protein in older men-A randomized clinical trial.

BACKGROUND: Due to increasing older populations worldwide, injuries, disabilities and deaths caused by falls among the elderly represent a growing human and societal problem. We aimed to improve health among men of at least 70 years of age with low-normal to low testosterone and mobility problems by using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium and protein. METHODS: This was a single-centre, randomized, placebo-controlled, double-blind trial with 148 older men with a median age of 77 (73-81) years, testosterone levels at median 8 (5-9) nmol/L (full range from 1.1 to 12.9 nmol/L) and mobility problems, recruited at University Hospital of Copenhagen, Herlev Hospital, Denmark. Participants were randomized into four arms for 20 weeks: (1) TU therapy (n = 37); (2) progressive resistance training with supplements of calcium, vitamin D and protein (n = 36); (3) both interventions combined (n = 36); or (4) no intervention (n = 39). The main outcome measure was the 30-s chair stand test, due to test performance correlating with the risk of serious fall injuries and lower extremity muscle strength. Outcome measurements were performed at baseline and after 20 weeks. RESULTS: After the intervention, the combination group receiving progressive resistance training, TU and supplements achieved a median score of 13 (11-15) compared to the control group at 10 (0-14) in the 30-s chair stand test (P = 0.003). This median improvement of 3.0 was clinically important. Compared to the control group, participants in the combination group also increased quality of life (P < 0.05) and reduced both tiredness (P < 0.05) and leg fat (P < 0.05) and had higher variability in the RR interval (P < 0.01). The group receiving TU reduced gynoid and leg fat compared to the control group (both P < 0.05). Blood tests improved for several variables, especially in the combination group. There was no statistically significant increase in adverse effects from either the supplements or training. CONCLUSIONS: In men ≥70 years old with low-normal to low testosterone and mobility problems, supplements of testosterone, calcium, vitamin D and protein combined with progressive resistance training improved 30-s chair stand test performance, muscle strength and quality of life. Both tiredness and leg fat were reduced, and RR interval variability was increased. Significant adverse effects were not observed.

Changes in Quality of Life and Sexual Function After Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Orchiectomy in Men With Metastatic Prostate Cancer: Results From a Randomized Trial.

Purpose To examine changes in quality of life (QoL) in men diagnosed with metastatic prostate cancer undergoing androgen deprivation therapy (ADT). Methods This was a phase IV trial where patients were randomized to either triptorelin or subcapsular orchiectomy. We report changes in QoL, functional and symptom scales, and sexual function. These were assessed using the validated questionnaires, namely, the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (EORTC-QLQ-C30), European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer 25 (EORTC-QLQ-PR25), and Erectile Hardness Scale (EHS) before treatment and at 12, 24, and 48 weeks, respectively. Data were analyzed using linear mixed models for repeated measures. Results Fifty-seven men with a median age of 74 years were randomized. The pooled analyses showed that QoL (p=0.003), emotional function (p<0.001), urinary symptoms (p=0.011), and hormonal treatment-related symptoms (p<0.001) changed significantly between visits. Improvement from baseline in QoL (mean change: 6.8 points (95% confidence interval (CI 95% CI): 2.1; 11.5)), emotional function (6.9 points: 3.3, 10.6), and urinary symptoms (-7.7 points (-12.3; -3.0)) was most pronounced at 24 weeks. Hormonal treatment-related symptoms (8.9 points (95% CI: 5.9; 12.0)) worsened. No significant differences between treatment groups were observed. At baseline, 29 men (51%) reported interest in sex, 18 were sexually active, and 12 had erections hard enough for penetration. At 48 weeks seven reported interest in sex, five were sexually active, and one man had a hard enough erection for penetration. Conclusions Men with newly diagnosed metastatic prostate cancer experience improved QoL and emotional function after starting ADT. Urinary symptoms improved, while hormonal treatment-related symptoms worsened. Interest in sex and sexual activity was retained in a proportion of men despite ADT.

Can nerve monitoring during radical prostatectomy improve functional outcomes? A randomised trial.

OBJECTIVE: To explore how the use of the ProPep® Nerve Monitoring System (ProPep Surgical, Austin, TX, USA) for intraoperative specific sparing of the pudendal nerve fibres influences postoperative functional outcomes after unilateral nerve-sparing (UNS) or non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We randomised 100 men undergoing UNS or NNS RARP to ProPep nerve monitoring during RARP (intervention) or standard of care RARP (control). Functional outcomes were assessed at 3, 6, and 12 months using the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the International Prostate Symptom Score, the Danish Prostate Symptom Score, the International Index of Erectile Function, the Erection Hardness Scale, and 24-h pad tests. The primary outcome was the difference in ICIQ-SF score between the groups at 12 months. Secondary outcomes included differences in the remaining outcome measures and continence rates at all time points. Continence was defined as the use of no pads and the answer 'Never' to the question: 'How often do you experience urinary incontinence?' or a urine loss of <8 g on the 24-h pad test. RESULTS: A total of 82 patients were included in the per-protocol analysis at 12 months with 41 in each group. At 12 months the mean ICIQ-SF scores were 5.37 (95% confidence interval [CI] 3.71-7.03) and 5.66 (95% CI 4.05-7.27) for the intervention and control groups, respectively (P = 0.8). There were no statistically significant differences in any of the remaining outcomes. However, the continence rate was higher in the intervention group at 6 months (63% vs 44%, P = 0.09). CONCLUSIONS: Intraoperative nerve monitoring did not result in better functional outcomes following UNS or NNS RARP. Larger studies are needed to explore if ProPep can reduce the time to continence after RARP.

Prevalence and predicting factors for commonly neglected sexual side effects to brachytherapy for prostate cancer: a cross-sectional observational study.

Background: Low-dose-rate brachytherapy (LDR-B) is an established treatment for localized prostate cancer. However, while erectile function is relatively well documented, other changes in sexual function are sparsely investigated. Aim: The study sought to investigate orgasmic dysfunction, urinary incontinence during sexual activity (UIS), changes in penile morphology, and sensory disturbances in the penis following LDR-B. Methods: A cross-sectional questionnaire-based study in patients who underwent LDR-B at our center from 2010 to 2020. The questionnaire included the International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and questions on orgasm, UIS, changes in penile morphology, and penile sensory disturbances. Outcomes: Outcomes were prevalence rates of altered perception of orgasm, orgasm associated pain, anejaculation, UIS, alterations in penile morphology, penile sensory disturbances, and predictors of these side effects. Results: Overall, 178 patients responded to the questionnaire. The median age was 70 years (range, 51-83 years), and the median time since LDR-B was 93 months (range, 21-141 months).Overall, 142 (80%) were sexually active and 126 (70.8%) had erectile dysfunction (ED). Of the sexually active patients, 8 (5.6%) reported anejaculation and 7 (4.9%) reported anorgasmia. Another 67 (46.9%) had decreased orgasmic intensity, while 69 (49.3%) reported an increased time to orgasm. Twenty-six (18.3%) patients had experienced orgasm-associated pain with a median visual analog pain score of 2. Considering overlap, 44 (31.0%) patients had an unchanged orgasmic function. Six (3.3%) patients had experienced UIS at least a few times. Penile length loss was reported by 45 (25.2%) patients. Seventeen (9.6%) patients reported an altered curvature of their penis and 9 (5%) had experience painful erection. Thirty-three (18.5%) patients had experienced decreased penile sensitivity. On multivariate analyses, ED was the only independent risk factor for altered perception of orgasm (odds ratio [OR], 6.6; P < .0001), orgasmic pain (OR, 5.5; P = .008), and penile shortening (OR, 4.2; P < .0056). No independent risk factors were identified for UIS or sensory penile disturbances. Clinical implications: Patients undergoing LDR-B should be adequately informed about possible side effects, and clinicians should inquire about these during follow-up visits. Strength and Limitations: We are the first to comprehensively explore the previously neglected side effects of LDR-B for prostate cancer. Limitations are the cross-sectional design assessing the cohort at different time points following their treatment and the response rate. Conclusions: Orgasmic dysfunction, changes in penile morphology, and sensory disturbances in the penis are common side effects of LDR-B for prostate cancer. UIS is only experienced by a small minority.

Management of functional outcomes after radical prostatectomy in the Nordic countries: A survey of uro-oncological centers.

We aimed to describe the clinical practice regarding erectile dysfunction and urinary incontinence after radical prostatectomy in the Nordic countries. A 37-item survey about pre- and post-prostatectomy evaluation and rehabilitation of sexual and urinary function was sent to 42 uro-oncology centers. Reporting was done according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Twenty-seven centers in Denmark (n = 6), Norway (n = 8), Finland (n = 7), and Sweden (n = 6) responded (64.3%). Post-prostatectomy sexual function was evaluated by 25 centers. The majority used validated questionnaires with significant variations across centers. Post-prostatectomy urinary function was evaluated by 24 centers. Again, the majority used validated questionnaires, while 9 centers used objective measures including uroflowmetry, residual urine volume, and pad usage. Twenty-one centers offered sexual rehabilitation and 12 of these described their protocols. All centers administered phosphodiesterase-5 inhibitors and seven centers offered further treatment options. Two centers offered a consultation with a sexologist. Twenty-three centers provided pelvic floor muscle training and one center used medical support with duloxetine. Our study indicates a need for standardized evaluation and management of erectile dysfunction and urinary incontinence following radical prostatectomy. Especially, there is a need for an increased focus on comprehensive sexual rehabilitation.

Robot-assisted radical cystectomy with intracorporeal urinary diversion: a Danish 11-year series.

OBJECTIVES: To evaluate the oncological and perioperative outcomes from a large, single-centre, robot-assisted radical cystectomy (RARC) cohort performed with intracorporeal urinary diversion (ICUD). PATIENTS AND METHODS: Patients who underwent RARC because of bladder cancer or recurrent carcinoma in situ from June 2009 until August 2020 at Herlev and Gentofte Hospital were prospectively and consecutively included. Kaplan-Meier survival analysis was used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). A Cox proportional hazards model was used to identify individual predictors of outcomes. Multiple logistic regression analysis was used to identify predictors of high-grade complications (Clavien-Dindo Grade ≥III). RESULTS: A total of 542 patients were included. The median (interquartile range) follow-up was 5.3 (2.73-8.06) years. In all, 78 patients (14%) were converted to open surgery; 15 (3%) during cystectomy and 63 patients (12%) were converted from ICUD to extracorporeal urinary diversion. The 5-year RFS, CSS and OS rates were 63% (95% confidence interval [CI] 59%-68%), 75% (95% CI 72%-80%) and 67% (95% CI 63%-72%), respectively. Pathological non-organ-confined disease (tumour stage >T2 or positive lymph nodes) predicted poorer RFS, CSS and OS. Reconstruction with a neobladder (20% of cases) compared to an ileal conduit was the only predictor of high-grade complications (odds ratio 2.54, 95% CI 1.46-4.43; P < 0.001). CONCLUSION: A RARC with ICUD is feasible as a standard surgical procedure for bladder cancer with only a few patients converted to open surgery. In our hands reconstruction with a neobladder was a strong predictor for high-grade complications.

Erectile Dysfunction Is Associated with Left Ventricular Diastolic Dysfunction: A Systematic Review and Meta-analysis.

CONTEXT: Erectile dysfunction (ED) is associated with an increased risk of cardiovascular morbidity and mortality. OBJECTIVE: To systematically review and analyze the cardiac structure and function in men with ED assessed with echocardiography. EVIDENCE ACQUISITION: We performed a systematic review and meta-analysis according to the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. We searched PubMed and the Cochrane Library on June 2, 2022, and included studies evaluating cardiac structure and function using echocardiography in men with ED compared with controls without ED. The Newcastle-Ottawa Quality Assessment Scale was used for assessing the quality of studies. We analyzed the mean differences in left ventricular ejection fraction (LVEF), the ratio of early transmitral filling velocity to early diastolic mitral annular velocity (E/e'), ratio of the early to late diastolic transmitral flow velocity (E/A), isovolumic relaxation time (IVRT), and left ventricular mass index (LVMi) in a random-effect model computed using means and standard deviations. The review was preregistered with PROSPERO (CRD42022337183). We received no funding. EVIDENCE SYNTHESIS: We included ten studies with 763 men diagnosed with ED (mean age: 55.6 yr) and 358 control men (mean age: 54.4 yr). E/e' was significantly worse in men with ED than in controls (mean absolute difference = 1.17, 95% confidence interval or CI [0.68, 1.65], p < 0.005). No significant differences were observed in LVEF, E/A, IVRT, or LVMi (-0.06, 95% CI [-1.06, 0.95], p = 0.91; -0.06, 95% CI [-0.24, 0.13], p = 0.55; 11.76, 95% CI [-0.88, 24.39], p = 0.07; and 4.37, 95% CI [-2.91, 11.65], respectively). The studies exhibited heterogeneity regarding study populations, reported echocardiography data, and variations in adjustments for confounding factors. CONCLUSIONS: Left ventricle diastolic dysfunction, as assessed by E/e', was more frequent in men with ED than in matched controls without ED. The results imply that echocardiography may be useful in the cardiovascular evaluation of men with ED to help identify myocardial impairment. PATIENT SUMMARY: This study reviewed for the first time previous research on cardiac structure and function in men with erectile dysfunction (ED), as assessed by echocardiography. We found that men with ED, compared with men without ED, had a higher ratio of early transmitral filling velocity to early diastolic mitral annular velocity , indicating a potentially higher rate of impaired diastolic function-a potential early indicator of heart disease. Identification of early signs of heart problems in men with ED may help initiate necessary lifestyle modifications or preventative therapies before the development of heart disease. However, more research is required to determine the clinical utility of using echocardiography as a risk assessment method.

Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression.

BACKGROUND: Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression. AIM: To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression. METHODS: We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay. RESULTS: The circulating concentrations of INSL3, testosterone, and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer. CONCLUSION: INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.

Exercise training to increase tumour natural killer-cell infiltration in men with localised prostate cancer: a randomised controlled trial.

OBJECTIVES: To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours. PATIENTS AND METHODS: A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56+ ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated. RESULTS: The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038). CONCLUSION: Preoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.

Erectile dysfunction and metabolic syndrome.

This review covers erectile dysfunction (ED) in men with metabolic syndrome. Men suffering from metabolic syndrome, and all its components, are at increased risk of ED. Men with ED should be metabolically screened with BMI, waist circumference, blood pressure, HbA1c and lipids. Components of the metabolic syndrome should be well-controlled as first step in treating ED using lifestyle changes and pharmaceutical therapies. Symptomatic treatments include phosphodiesterase type 5 inhibitors, penile injections, intraurethral medication, vacuum pumps and penile implants.

Fatigue, health-related quality-of-life and metabolic changes in men treated with enzalutamide or abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer: A randomised clinical trial (HEAT).

INTRODUCTION: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC). Herein, we compare fatigue, health-related quality-of-life (HRQoL) and metabolic changes in men with mCRPC treated with enzalutamide and AAP. MATERIALS AND METHODS: In this single-centre, open-labelled, phase IV trial, patients with metastatic prostate cancer progressing on androgen deprivation therapy were randomly assigned to enzalutamide (160 mg daily) or AAP (1000 mg abiraterone acetate and 10 mg prednisone daily) as first-line mCRPC treatment. The primary outcome was the difference in changed fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire). The secondary outcomes were differences in changed HRQoL (Functional Assessment of Cancer Therapy-Prostate questionnaire), body composition, weight, glucose homeostasis, lipid profile and blood pressure. All outcomes were assessed at baseline and at 12-week follow-up. TRIAL REGISTRATION: clinicaltrialsregister.eu (2017-000099-27). RESULTS: 170 patients were randomised (1:1) to enzalutamide or AAP. The primary outcome was positive with a clinically meaningful difference in fatigue, favouring AAP (3.4 points, 95% CI 1.2; 5.6, P = 0.003). The group difference in changed HRQoL did not reach clinical significance. The most important metabolic finding was a higher increase in glycated haemoglobin (HbA1c) for AAP than enzalutamide (3.4 mmol/mol, 95% CI 2.1; 4.8, P = 0.001). Eight patients developed type 2 diabetes (T2D) in the AAP group and none in the enzalutamide group. No treatment-related serious adverse event was observed. CONCLUSIONS: AAP resulted in less fatigue than enzalutamide in a randomised setting. This was at the expense of a higher HbA1c increase and incidence of T2D.

Delivering Physical Activity Recommendations in Daily Clinical Cancer Care: An Observational Interview Study in Prostate Cancer Out-Patient Clinics Using an Empirical Ethics of Care Approach.

Physical activity (PA) has shown to mitigate many of the common side effects of cancer treatments. The promotion of PA by health care professionals (HCPs) can facilitate the adoption of PA by patients with cancer. Drawing on an empirical ethics of care approach, this article explores how the delivery of PA recommendations is done within clinical cancer care. Based on 175 observations of consultations between doctors, nurses and patients and interviews with 27 doctors and nurses, we show how delivering PA recommendations was related to four care practices: "adjusting information to match the patient's needs and situation," "managing current and anticipated treatment-induced side effects," "using visual aids and quantifiable data," and "maintaining a good relationship between the patient and the HCP." Drawing on these findings, we discuss strategies to strengthen the delivery of PA recommendations in clinical cancer care.

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol.

INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. METHODS AND ANALYSIS: In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. ETHICS AND DISSEMINATION: This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.

Interpretation of composite endpoints in urology: an analysis of citation quality.

OBJECTIVE: To investigate how urological studies using composite endpoints as the primary outcome were cited. MATERIALS AND METHODS: In this quality analysis of citations, three randomized clinical trials each investigating oncological and non-oncological urology were selected for citation analysis based on pre-defined criteria. In total, 531 papers citing the selected studies were reviewed; citations were evaluated based on whether they correctly referred to the composite endpoint and if singleton endpoints were defined and/or discussed. RESULTS: Among the citations, 223/531 (42%) referred to the composite endpoint, of which 217/223 (97.3%) correctly cited the composite endpoint. However, only 91/217 (41.9%) defined and/or discussed the singleton endpoints of the composite endpoint. The lack of a validated instrument for citation analysis was a limitation of this study. Meanwhile, the main strength is the large number of individually analyzed citations. CONCLUSIONS: The composite endpoints of urological randomized clinical trials are generally cited without referring to the composite endpoint; when cited, the composite endpoints are described correctly. However, in most cases, without defining or discussing the singleton endpoints.

Quality of life in men with metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone: a systematic review and meta-analysis.

BACKGROUND: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC), but different mechanisms of action. The aim was to compare patient-reported health-related quality of life (HRQoL) in men treated with enzalutamide vs AAP for mCRPC. METHODS: We systematically reviewed the literature in June 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Patient-reported outcomes (PROs) until the last follow-up were summarised in a narrative synthesis. Short-term changes (12 weeks) in HRQoL, measured by the Functional Assessment of Cancer Therapy-Prostate total score (FACT-P), were compared between treatment groups and were analysed for enzalutamide and AAP in separate meta-analyses. Higher FACT-P scores indicate better HRQoL. RESULTS: Eight studies were included in the systematic review, four of which were randomised clinical trials (RCTs) eligible for the meta-analyses. The meta-analyses showed mean within-subject FACT-P changes from baseline to week 12 of -1.3 points (95% confidence interval [CI] -2.7; 0.1) for enzalutamide and 4.7 points (95% CI -0.1; 9.6) for AAP. One RCT and three non-randomised studies directly compared enzalutamide with AAP. The RCT showed better short-term HRQoL for AAP (6.8 FACT-P-points, 95% CI 1.7; 11.8) and better long-term HRQoL for AAP in men ≥75 years (7.35 FACT-P-points, 95% CI 2.59; 12.11). The non-randomised studies showed no difference in long-term HRQoL but had all a serious risk of bias. Limitations of the included studies include that the PRO in the included trials were inconsistently reported and that only one study defined the HRQoL measures in their published protocol. CONCLUSIONS: AAP seems to be associated with better short-term HRQoL than enzalutamide. This difference was not apparent at longer follow-up, but the long-term studies had serious risks of bias.

Safety and Effects of Football in Skeletal Metastatic Prostate Cancer: a Subgroup Analysis of the FC Prostate Community Randomised Controlled Trial.

BACKGROUND: Skeletal metastatic disease excludes many cancer patients from participating in exercise and physical activity due to safety concerns. Empirical evidence from high-quality trials is warranted to guide clinicians and patients. OBJECTIVE: To evaluate the safety and potential benefits of high-impact aerobic exercise in patients with prostate cancer with skeletal metastases. DESIGN: Exploratory subgroup analysis of a pragmatic, multicentre, parallel randomised controlled trial. SETTING: The trial recruited 214 patients from five hospital urological departments in Denmark. PARTICIPANTS: Patients with prostate cancer with skeletal metastases (n = 41). INTERVENTION: Six months of football training twice weekly at a local club or usual care. Both groups received brief information on physical activity recommendations at the time of randomisation. MAIN OUTCOME(S) AND MEASURE(S): Safety, defined as falls, fractures and hospital admissions. Effects were evaluated on the primary outcome (prostate cancer-specific quality of life) and secondary outcomes (lean body mass, fat mass, hip and spine bone mineral density, and general physical and mental health). RESULTS: The original trial comprised 214 participants, 41 of whom had skeletal metastases at enrolment. Of these, 22 were allocated to football and 19 to usual care. The trial retention rate was 95% at 12 weeks and 88% at 6 months. Football participants attended 13 sessions on average at 12 weeks and 23 at 6 months. There were two falls, one in each group after 6 months, and no fractures. There were four unplanned hospital admissions in the study period, all four in the usual care group. Statistically significant between-group difference was observed in the primary outcome change in prostate cancer-specific quality of life at 12 weeks (7.6 points [95% CI 0.5 to 15.0]; P = 0.038). No statistical changes were found in the secondary outcomes. CONCLUSION: The analysis showed that football training was safe in patients with skeletal metastatic prostate cancer and significantly improved quality of life. Larger analyses and/or trials are warranted to confirm the safety of exercise more broadly in cancer patients with skeletal metastatic disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02430792 . Date of registration 30 April 2015.

Antisense oligonucleotides and nucleic acids generate hypersensitive platelets.

INTRODUCTION: Despite the great promise for therapies using antisense oligonucleotides (ASOs), their adverse effects, which include pro-inflammatory effects and thrombocytopenia, have limited their use. Previously, these effects have been linked to the phosphorothioate (PS) backbone necessary to prevent rapid ASO degradation in plasma. The main aim of this study was to assess the impact of the nucleic acid portion of an ASO-type drug on platelets and determine if it may contribute to thrombosis or thrombocytopenia. METHODS: Platelets were isolated from healthy donors and men with advanced prostate cancer. Effects of antisense oligonucleotides (ASO), oligonucleotides, gDNA, and microRNA on platelet activation and aggregation were evaluated. A mouse model of lung thrombosis was used to confirm the effects of PS-modified oligonucleotides in vivo. RESULTS: Platelet exposure to gDNA, miRNA, and oligonucleotides longer than 16-mer at a concentration above 8 mM resulted in the formation of hypersensitive platelets, characterized by an increased sensitivity to low-dose thrombin (0.1 nM) and increase in p-Selectin expression (6-8 fold greater than control; p < 0.001). The observed nucleic acid (NA) effects on platelets were toll-like receptor (TLR) -7 subfamily dependent. Injection of a p-Selectin inhibitor significantly (p = 0.02) reduced the formation of oligonucleotide-associated pulmonary microthrombosis in vivo. CONCLUSION: Our results suggest that platelet exposure to nucleic acids independent of the presence of a PS modification leads to a generation of hypersensitive platelets and requires TLR-7 subfamily receptors. ASO studies conducted in cancer patients may benefit from testing the ASO effects on platelets ex vivo before initiation of patient treatment.

Reliability of graded cycling test with talk test and 30-s chair-stand test in men with prostate cancer on androgen deprivation therapy.

PURPOSE: To investigate the absolute and relative reliability of the "graded cycling test with talk test" (GCT-TT) and the "30-second chair-stand test" (30s-CST) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: Men with prostate cancer on ADT were included in this test-retest study. GCT-TT and 30s-CST were performed twice with 1 hour between test sessions. All tests were conducted by two experienced physiotherapists and all patients were familiar with the tests. Only intra-tester reliability was investigated as the test and retest of each participant were performed by the same physiotherapist. Intraclass correlation coefficient (ICC2.1), standard error of measurement (SEM and SEM95), and smallest real difference (SRD) were calculated. RESULTS: Sixty men were included with a mean age of 70.8 ± 6.6 (mean ± SD) years. All performed 30s-CST twice without any problems. Two participants were excluded from the analysis of the GCT-TT results. Relative reliability for 30s-CST (ICC2.1) was 0.97 [95% CI: 0.94-0.98] with low measurement error: SEM95, 1.9 repetitions, and SRD, 2.6 repetitions. The corresponding results for GCT-TT were ICC2.1, 0.90 [95% CI: 0.84-0.94]; SEM95, 19.9 W; and SRD, 28.2 W. CONCLUSIONS: The reliability of 30s-CST and GCT-TT is substantial for men with prostate cancer receiving ADT. Overall, an average 30s-CST improvement of 1.9 repetitions on a group level and three repetitions for individual patients are considered real improvements. A GCT-TT improvement exceeding 19.9 W represents a real improvement for a group of patients. Individual patients need to improve two steps (30 W).