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.

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.

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.

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).

Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) administered against metastatic prostate cancer has significant side effects including sexual dysfunction. AIM: To assess sexual interest and motivators for sex during ADT and to find out what model of sexuality best describes the sexual experience for men during this treatment. METHODS: A questionnaire was mailed to patients who had received ADT for ≥6 months. Patients were asked to choose all relevant entities from a list of sexual motivators and between models of sexuality described by Masters and Johnson (excitement and physical experiences), Kaplan (sexual desire), and Basson (intimacy and closeness to partner). Erectile function was assessed by the Erection Hardness Scale, and sexual satisfaction was measured on a scale from 0 to 10. OUTCOMES: Sexual activity, erectile function, sexual satisfaction, and motivators for sexual interest in the study subjects as well as the proportion of participants who endorsed either of the 3 models of sexuality. RESULTS: A total of 173 men were invited, and 76 returned the questionnaires (44%). The median age was 76 (range 69-80) years, and the median duration of ADT was 30 months. A total of 62 men had been sexually active before ADT, and of these, 2 were still active. Another 29 were interested in sexual activity. 3 men endorsed the Masters and Johnson model, whereas the remaining participants did not endorse any of the models. The motivators for sexual interest were feeling an emotional connection to the partner (n = 16), sexual desire (n = 10), satisfaction of the partner (n = 8), fear that the partner would leave (n = 4), achieving orgasm (n = 3), and a desire to feel masculine (n = 1). No one was interested in sexual activity to reduce stress or to maintain confidence. Only 1 patient had erections sufficient for penetrative intercourse, and the median sexual satisfaction for the entire group was 0 (interquartile range: 0-5). CLINICAL IMPLICATIONS: Sexuality and sexual function should be addressed in men undergoing ADT. STRENGTHS & LIMITATIONS: The main strength of our study is that we are the first to explore both motivators for sexual activity and endorsement of sexual models in men undergoing ADT. The study is limited by the relatively low number of participants and the response rate of 44%. CONCLUSION: ADT is detrimental to sexual function. However, many patients maintain an interest in sexual activity, which does not fit our established models. Rather, factors such as keeping an emotional connection with a partner play a role. Fode M, Mosholt KS, Nielsen TK, et al. Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer. J Sex Med 2020;17:1538-1543.

Community-based football in men with prostate cancer: 1-year follow-up on a pragmatic, multicentre randomised controlled trial.

BACKGROUND: Physical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted. METHODS AND FINDINGS: We conducted a pragmatic, multicentre, parallel randomised controlled trial in 5 Danish urological departments. Recruitment began in May 2015, the first participant was randomised in June 2015, and the last participant was included in February 2017. In total, 214 men with prostate cancer were randomly assigned to either 6 months of free-of-charge football training twice weekly at a local club (football group [FG]) (n = 109) or usual care (usual care group [UG]) (n = 105), including brief information on physical activity recommendations at randomisation. Participants were on average 68.4 (SD 6.2) years old, 157 (73%) were retired, 87 (41%) were on castration-based treatment, 19 (9%) had received chemotherapy, and 41 (19%) had skeletal metastases at baseline. In this 1-year follow-up study, we evaluated the effects of community-based football training on the following outcomes: primary outcome, quality of life; secondary outcomes: continuation of football after 6 months, hip and lumbar spine bone mineral density (BMD), mental health score, fat and lean body mass, and safety outcomes, i.e., fractures, falls, and hospital admissions. Intention to treat (ITT) and per protocol (PP) analyses were conducted. No statistically significant between-group difference was observed in change in prostate-cancer-specific quality of life (ITT: 1.9 points [95% CI -1.9 to 5.8], p = 0.325; PP: 3.6 points [95% CI -0.9 to 8.2], p = 0.119). A statistically significant between-group difference was observed in change in total hip BMD, in favour of FG (0.007 g/cm2 [95% CI 0.004 to 0.013], p = 0.037). No differences were observed in change in lumbar spine BMD or lean body mass. Among patients allocated to football, 59% chose to continue playing football after the end of the 6-month intervention period. At 1-year follow-up in the PP population, FG participants had more improvement on the Mental Component Summary (2.9 [95% CI 0.0 to 5.7], p = 0.048 points higher) than UG participants, as well as a greater loss of fat mass (-0.9 kg [95% CI -1.7 to -0.1], p = 0.029). There were no differences between groups in relation to fractures or falls. Hospital admissions were more frequent in UG compared to FG (33 versus 20; the odds ratio based on PP analysis was 0.34 for FG compared to UG). There were 3 deaths in FG and 4 in UG. Main limitations of the study were the physically active control group and assessment of physical activity by means of self-report. CONCLUSIONS: In this trial, participants allocated to football appeared to have improved hip BMD and fewer hospital admissions. Men who played football more than once a week for 1 year lost fat mass and reported improved mental health. Community-based football proved to be acceptable, even when club membership was not subsidised. TRIAL REGISTRATION: ClinicalTrials.gov NCT02430792.

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.

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.

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.

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.

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.

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.

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.

Diagnostic value of probe-based confocal laser endomicroscopy versus conventional endoscopic biopsies of non-muscle invasive bladder tumors: a pilot study.

PURPOSE: The standard procedure for diagnostics and follow-up for non-muscle invasive bladder cancer (NMIBC) is cystoscopy in the outpatient clinic. Suspicious lesions are biopsied for histopathological assessment. This pilot study aimed to evaluate the ability of Confocal Laser Endomicroscopy (CLE) to rule out High Grade Urothelial Carcinoma (HGUC) to select patients for in-office fulguration. MATERIALS AND METHODS: We performed a prospective non-randomized, single surgeon study. Intraoperative CLE was performed independently by the surgeon and a blinded on-site uropathologist. Following the procedure, a CLE evaluation was performed by another blinded urologist. Lesions were classified as normal/inflammatory, Low Grade Urothelial Carcinoma (LGUC) or HGUC. With the histological evaluations as the gold standard we calculated sensitivity, specificity, PPV and NPV for HGUC and the accuracy for each CLE assessor. The primary outcome was the NPV for HGUC for the surgeon. RESULTS: Twelve patients with a total of 34 lesions were included. Six lesions were flat and 28 were exophytic. On histopathology, 25 lesions were classified as normal/inflammatory or LGUC, while nine were classified as HGUC. For the surgeon, the uropathologist and the second urologist, the sensitivity was 44%, 78% and 22%, respectively. Specificities for the three observers were 84%, 68% and 96%. This corresponded to PPVs for HGUC of 50%, 47% and 67% and NPV for HGUC of 81%, 89% and 77%. CONCLUSIONS: In our hands the NPV of CLE is not high enough for it to be considered an alternative to histopathological assessment of bladder lesions.

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.

Sildenafil in postprostatectomy erectile dysfunction (perspective).

Erectile dysfunction (ED) is a common side effect to radical prostatectomies, even with nerve-sparing procedures. To ameliorate the problem so-called "penile rehabilitation" programs have been developed. The most widely used method of this is subscribing sildenafil or other PDE5-inhibitors to patients following surgery. This is based on a theory that these drugs may increase penile oxygenation and provide antiapoptotic factors (primarily NO and cGMP), thus protecting the penile tissue in a period with reduced nerve function following the surgery. Preclinical studies have confirmed the potential of sildenafil in this context and early human trials have suggested that a steady ingestion of sildenafil might protect the structural integrity of the penis. However, subsequent well-designed trials have not been able to confirm the initial findings. This fits well with sildenafil's mechanism of action because it does not actually induce erections or the production of either nitric oxide or cGMP. Rather, the drug enhances effects of an erectile response induced by neurotransmitters from the cavernous nerves. Therefore, sildenafil should no longer be offered as a sole means of penile rehabilitation. Rather, more research is needed, and clinicians need to apply a broader concept of sexual rehabilitation in postprostatectomy ED.

Fatigue, quality of life and metabolic changes in men treated with first-line enzalutamide versus abiraterone plus prednisolone for metastatic castration-resistant prostate cancer (HEAT): a randomised trial protocol.

INTRODUCTION: Enzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection relies on patient choice, cost and side effects. The aim of this randomised trial is to investigate differences in fatigue, health-related quality of life (HRQoL) and metabolic side effects in men with mCRPC treated with first-line enzalutamide versus AAP. METHODS AND ANALYSIS: In this ongoing open-label randomised (1:1) clinical trial, enzalutamide is compared with AAP as first-line treatment for men with mCRPC. The primary endpoint is fatigue assessed with the questionnaire Functional Assessment of Chronic Illness Therapy-Fatigue version 4. Secondary endpoints are changes in body composition (ie, fat mass, visceral adipose tissue, subcutaneous adipose tissue and lean body mass assessed with dual energy X-ray absorptiometry), glucose metabolism assessed with a 2-hour oral glucose tolerance test, serum lipids, blood pressure and HRQoL assessed with the questionnaire Functional Assessment of Cancer Therapy-Prostate (FACT-P). All study endpoints are assessed at baseline and 12-week postintervention. Blood and urine samples are collected at baseline and at time of progression on allocated treatment for future investigation of predictive and prognostic biomarkers in prostate cancer treatment. The planned sample size is 170 participants. All participants are recruited from Herlev and Gentofte Hospital, Denmark. Estimated last patient's last visit is February 2020. ETHICS AND DISSEMINATION: The study received project approval from the National Committee on Health Research Ethics and Danish Data Protection Agency and Danish Medicines Agency (EudraCT no.: 2017-000027-99). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums. TRIAL REGISTRATION NUMBER: Clinicaltrialsregister.eu (2017-000099-27).