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.

Neglected side effects to curative prostate cancer treatments.

In this narrative review we summarize neglected side effects of curative intended treatment for prostate cancer. They include climacturia, arousal incontinence (AI), orgasmic disturbances such as altered orgasmic sensation, anorgasmia, and orgasm-associated pain (dysorgasmia), ejaculatory dysfunction, and morphological penile alterations in the form of shortening and deformity. Even though they have not received as much interest as erectile dysfunction (ED) or urinary incontinence, these side effects have been shown to negatively impact patient's quality of life. They are common and rates of climacturia after radical prostatectomy (RP) range from 20% and 45%, less after external beam radiation therapy (EBRT). Decreased orgasmic sensation ranges from 3.9% to 60% after RP and between 36-57% after EBRT. Dysorgasmia ranges from 9.5-15% for both RP and EBRT. Anejculation after EBRT ranges from 11-71% and rates of penile shortening are reported between 0 and 100%. There are no internationally validated questionnaires that adequately asses these side effects. This is necessary if we are to align patient and partner expectations properly and consequently manage them optimally. Neglected side effects should be discussed with patients and their partners preoperatively, as they are associated with bother and may lead to patient's avoiding sexual activity.

Quality of Information in YouTube Videos on Erectile Dysfunction.

INTRODUCTION: Many patients seek information online including on social media. AIM: To assess the quality of information regarding erectile dysfunction (ED) in YouTube videos. METHODS: We searched "erectile dysfunction" on YouTube in October 2019 and evaluated the first 100 videos in English sorted by relevance. MAIN OUTCOME MEASURE: We recorded the user engagement, video producer, intended audience, and content. Videos containing medical information were evaluated using the Patient Education Materials Assessment Tool (PEMAT) and the DISCERN quality criteria for consumer health information. The PEMAT evaluates the understandability and actionability of materials as a percentage. The DISCERN assesses the quality of information by a scale from 1 (serious or extensive shortcomings) to 5 (minimal shortcomings). RESULTS: The median number of total views was 22,450 (range 591-20,255,133) and the median number of views/month was 654 (range 9-723,398). 42 percent of the videos were posted by professional medical institutions, and 21% were posted by individual medical professionals. Most videos were aimed at the general public or patients suffering from ED. The median PEMAT understandability and actionability scores were both 100% (range 50-100% and 33-100%, respectively). The median DISCERN score was 2 (range 1-5) with 80.4% receiving a score of ≤3. Overall, 28% of the videos contained direct misinformation. DISCERN scores were higher in videos produced by medical institutions (P = .0104), not selling specific products (P = .007) and not promoting alternative medicine (P = .0002). The number of subscribers was an independent predictor of views/month (P < .0001). CONCLUSION: Patients may be exposed to videos of poor quality when searching for information about ED on YouTube. The medical community needs to adapt a strategy to improve the quality of online medical information. Fode M, Nolsøe AB, Jacobsen FM, et al. Quality of Information in YouTube Videos on Erectile Dysfunction. J Sex Med 2020;8:408-413.

The Impact of Testicular Torsion on Testicular Function.

Torsion of the spermatic cord is a urological emergency that must be treated with acute surgery. Possible long-term effects of torsion on testicular function are controversial. This review aims to address the impact of testicular torsion (TT) on the endocrine- and exocrine-function of the testis, including possible negative effects of torsion on the function of the contralateral testis. Testis tissue survival after TT is dependent on the degree and duration of TT. TT has been demonstrated to cause long-term decrease in sperm motility and reduce overall sperm counts. Reduced semen quality might be caused by ischemic damage and reperfusion injury. In contrast, most studies find endocrine parameters to be unaffected after torsion, although few report minor alterations in levels of gonadotropins and testosterone. Contralateral damage after unilateral TT has been suggested by histological abnormalities in the contralateral testis after orchiectomy of the torsed testis. The evidence is, however, limited as most human studies are small case-series. Theories as to what causes contralateral damage mainly derive from animal studies making it difficult to interpret the results in a human context. Large long-term follow-up studies are needed to clearly uncover changes in testicular function after TT and to determine the clinical impact of such changes.

Hormone naïve metastatic prostate cancer: How to treat it?

OBJECTIVES: Recent landmark studies (GETUG-AFU 15, CHAARTED, STAMPEDE (docetaxel), LATITUDE and STAMPEDE (abiraterone)) have changed the treatment of hormone sensitive metastatic prostate cancer (mHSPC) from androgen deprivation therapy (ADT) only to combined therapy with either docetaxelor abiraterone acetate plus prednisone (AAP) together with ADT. In this Review we highlight current evidence and recommendations on how to treat men with newly diagnosed mHSPC beyond ADT. METHODS: Narrative overview of available evidence retrieved from pubmed searches, hand searches and authoritative texts. RESULTS: Docetaxel or AAP in combination with ADT improves overall survival (OS) in men fit for combined treatment presenting with newly diagnosed mHSPC. The strongest evidence is for men with high volume mHSPC (four or more bone metastases with at least one outside the axial skeleton and/or visceral metastases) or mHSPC with high risk features (A minimum of two out of three following high-risk features: Gleason score ≥ 8, ≥ 3 bone lesions or visceral metastasis) as per CHAARTED and LATITUDE criteria, respectively. While upfront docetaxel and AAP yield comparable OS improvement, docetaxel has not been shown to increase OS specifically for men with low volume/low risk mHSPC, whereas, a recent post-hoc analysis from the STAMPEDE (abiraterone) trial showed consistent overall survival benefit of AAP plus ADT independent of risk stratification. While these data are limited by their retrospective nature, they do suggest that patients with low-risk mHSPC should be offered AAP. In men with high volume/high risk mHSPC, choosing between six-cycles of docetaxel or AAP until disease progression relies on patient preference, cost and individual assessment of which drug side-effect profile is most suitable. CONCLUSION: Offer men presenting with newly diagnosed mHSPC fit enough for combined therapy either ADT plus docetaxel or AAP.

OBJETIVOS: Estudios de referencia recientes (GETUG-AFU 15, CHAARTED, STAMPEDE (docetaxel), LATITUDE y STAMPEDE (abiraterone)) han cambiado el tratamiento del cáncer de próstata hormonosensible metastásico (CPHSm) de la terapia de deprivación androgénica sola a la terapia combinada bien con docetaxel o abiraterona acetato y prednisona junto con deprivación androgénica. En esta revisión, destacamos la evidencia actual y recomendaciones sobrecómo tratar a los hombres con CPHSm de reciente diagnóstico más allá de la deprivación androgénica.MÉTODOS: Repaso narrativo de la evidencia disponible obtenida por busquedas en PubMed, búsquedas manuales y textos fidedignos. RESULTADOS: Docetaxel o abiraterona más prednisona en combinación con deprivación androgénica mejoran  la supervivencia global (SG) en pacientes adecuados para tratamiento combinado que presentan un CPHSm de reciente diagnóstico. La mejor evidencia es en varones con CPHSm de alto volumen (cuatro o más metástasis óseas con al menos una fuera del esqueleto axialy/o metástasis viscerales) o CPHSm con características de alto riesgo (un mínimo de dos de las tres siguientes características de alto riesgo: Puntuación de Gleason≥ 8, ≥ 3 lesiones óseas o metástasis viscerales) según los criterios de CHAARTED y LATITUDE respectivamente. Aunque docetaxel inicial y abiraterona más prednisona ofrecen una mejora comparable de la supervivenciaglobal, docetaxel no ha demostrado que mejore la supervivencia global específicamente en hombres con CPHSm de bajo volumen/bajo riesgo; mientras que un reciente análisis post-Hoc del estudio STAMPEDE (Abiraterona) mostró un beneficio consistente en supervivencia global de abiraterona más prednisona junto con deprivación androgénica independientemente de la estratificación por riesgo. Aunque estos datos están limitados por su naturaleza retrospectiva, sugieren que a los pacientes con CPHSm de bajo riesgo debería ofrecérseles abiraterona más prednisona. En varones con CPHSm de alto volumen/alto riesgo, elegir entre seis ciclos de docetaxel o abiraterona-prednisona hastaque la enfermedad progrese se basa en la preferencia del paciente, el coste y la evaluación individual sobre qué perfil de efectos colaterales farmacológicos es más adecuado. CONCLUSIONES: Ofrecer terapia de deprivación andrógénica con docetaxel o abiraterona + prednisona a los pacientes que presentan un CPHSm de recientediagnóstico.

Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study.

OBJECTIVES: To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin-releasing hormone (GnRH) agonist and those treated with orchiectomy. PATIENTS AND METHODS: Fifty-eight hormone-naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks. The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], lean body mass [LBM] and android/gynoid fat [AG] ratio) assessed with dual X-ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between-group differences. RESULTS: No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [CI] -0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm3 , 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance (P < 0.001). No differences in changed VAT, LBM or AG ratio were observed between the groups. The pooled analyses, combining data from both groups, showed androgen deprivation therapy (ADT) to significantly increase fat mass, SAT, VAT, serum cholesterols (total, high-density lipoprotein and low-density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12-24 weeks of ADT. CONCLUSIONS: Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12-24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with GnRH agonists and that these increases are associated with an increase in insulin resistance.

Results of 14 years of brachytherapy for localized prostate cancer in Denmark: the Herlev cohort.

OBJECTIVE: Brachytherapy is one of several curative treatments for localized prostate cancer (PCa). The objective of this study was to report biochemical recurrence-free survival (BRFS), metastatic-free survival (MFS) and PCa-specific mortality after low-dose brachytherapy, stratified according to the D'Amico risk classification in a large Danish cohort. MATERIALS AND METHODS: The study population comprised 502 men treated with brachytherapy in 1998-2012. BRFS was defined by the Phoenix criteria. Kaplan-Meier survival analysis was used to estimate BRFS and MFS. The cumulative PCa mortality was analysed using competing risk analyses. Multivariable Cox regression analysis was used to estimate risk of biochemical recurrence. RESULTS: In total, 206 men were classified with low-risk PCa, 265 men with intermediate-risk PCa and 33 men with high-risk PCa. Median follow-up was 6.6 years [95% confidence interval (CI) 6.2-7.0]. The 10 year BRFS was 90% (95% CI 83-97), 75% (95% CI 65-87) and 75% (95% CI 59-92) in men with low-, intermediate- and high-risk PCa, respectively. The 10 year MFS was 95% (95% CI 89-100), 93% (95% CI 88-98) and 78% (95% CI 57-99) in men with low-, intermediate- and high-risk PCa, respectively. The 10 year cumulative incidence of PCa mortality was 1% (95% CI 0-3), 5% (95% CI 0-12) and 11% (95% CI 0-25) for men with low-, intermediate- and high-risk PCa, respectively. CONCLUSIONS: Low-dose brachytherapy offers good short- to intermediate-term cancer control in selected men with localized PCa. Further studies are needed for safety analyses and for comparison with other treatment modalities.

Male infertility problems of patients with strict sperm morphology between 5-14% may be missed with the current WHO guidelines.

OBJECTIVE: In 2010 W.H.O. changed the lower reference limit for strict sperm morphology from 15 to 4%. The change was based on 5th percentile cut points from a meta-analysis on a published series of fertile men. This study investigates if patients referred for evaluation with sperm morphologies between 5-14% have identifiable etiologies of male infertility. MATERIALS AND METHODS: I.R.B. approval was obtained to review records for patients referred to the University of Michigan Center of Reproductive Medicine between May 2012-May 2014 whom had a sperm morphology of 5-14%. Semen analysis, hormone levels, and information related to an infertility diagnosis, were recorded into a de-identified database. Patients were placed into the categories 'Varicocele', 'Hypogonadism', 'Intercourse problems', 'Anti-sperm antibodies (A.S.A.)', 'Other' or 'No diagnosis'. RESULTS: A total of 253 patients were included in the study. Of these, 96/253 (38%) had a clinical varicocele; 44/253 (17%) hypogonadism; 4/253 (2%) intercourse problems; 11/253 (4%) evidence of sperm antibodies; and 15/253 (6%) had various other problems deemed potentially contributing causes of infertility. In all, nearly 67% of the subjects were identified to have a potential contributing etiology of male infertility. Similar results were found for the men with isolated low morphology (n = 194). CONCLUSIONS: This study demonstrates that 67% of men in infertile couples, who have strict sperm morphology between 5 and 14%, are found to have a potential contributing male factor infertility diagnosis. This raises the possibility that the new lower reference value for sperm morphology may result in missed opportunities for proper infertility assessment.

Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial.

PURPOSE: Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin. MATERIALS AND METHODS: In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24-week depot injections. Androgen status was measured by liquid chromatography-tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression. RESULTS: Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2-41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups. CONCLUSIONS: The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.