Results from the first autologous grafting of adult human testis tissue: a case report.

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.

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.

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.

Evaluation of a re-engineered device for penile vibratory stimulation in men with spinal cord injury.

STUDY DESIGN: Cohort study OBJECTIVES: The purpose of this study was to evaluate the performance of a re-engineered device (Ferticare 2.0), which is replacing the previous standard (Ferticare 1.0) for penile vibratory stimulation in men with spinal cord injury. Most men with spinal cord injury are anejaculatory, requiring medical assistance to obtain their semen. Penile vibratory stimulation is generally recognized as the standard of care for semen retrieval in these anejaculatory men. SETTING: Major Research University in Miami, Florida, USA. METHODS: The Ferticare 2.0 device was applied to 15 men with spinal cord injury in a three-step protocol simulating normal use. Step 1: one device (2.5 mm amplitude, 100 Hz) was applied to the glans penis for 2 min. Step 2: If no ejaculation occurred, the amplitude was increased to 4.0 mm (100 Hz) and the device similarly applied. Step 3: If no ejaculation occurred, two devices, each 2.5 mm and 100 Hz were applied to the dorsum and frenulum of the glans penis. Participants at risk for autonomic dysreflexia were pretreated with sublingual nifedipine (20 mg), 15 min prior to stimulation. Blood pressure and other symptoms of autonomic dysreflexia were monitored. Participants answered a questionnaire about their experience with the device. RESULTS: Thirteen of 15 participants ejaculated with the device. No adverse events occurred. All participants commented they would recommend the device to other men with spinal cord injury. CONCLUSIONS: A re-engineered device, the Ferticare 2.0, is safe and effective for inducing ejaculation in men with spinal cord injury.

Patient-reported outcomes from a single-centre prospective post-marketing study on Collagenase Clostridium Histolyticum injections for Peyronie's disease.

The aim of this study was to evaluate patient-reported outcomes of Collagenase Clostridium Histolyticum (CCHi) for Peyronie's Disease. Patients treated with 2-4 cycles of CCHi between 01/2016 and 08/2018 were asked to fill out the "bother domain" of the Peyronie's Disease Questionnaire (PDQ) at scheduled appointments for injections. CCHi cycles involved two injections (0.58 mg) separated by 48-72 hr. During the study, 34 patients were treated, seven patients were excluded due to incomplete baseline values. Mean (standard deviation) PDQ bother domain baseline score was 11.1 (2.6). ANOVA demonstrated statistically significant effects of injections (p < .001) with a decrease in PDQ bother domain scores 6 weeks after the 1st cycle (9.9 [3.3], p = .013), 6 weeks after the 2nd cycle (8.2 [4.0], p = .009) and 6 weeks after the 3rd cycle (6.5 [3.6], p < .001). After 2-4 cycles of CCHi treatment, patients reported changes in penile curvature as "Worse" (0), "No Change" (2), "Little decrease" (10), Decrease (10) and "Significant decrease" (4). After completion of CCHi treatment, 82% of patients still reported that vaginal intercourse was difficult or impossible. Patients with Peyronie's Disease undergoing CCHi treatment reported statistically significant decreases in PDQ bother domain scores. However, most patients still report difficulty with intercourse after treatment.

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.

"Kicked out into the real world": prostate cancer patients' experiences with transitioning from hospital-based supervised exercise to unsupervised exercise in the community.

PURPOSE: Regular exercise is recommended to mitigate the adverse effects of androgen deprivation therapy in men with prostate cancer. The purpose of this study was to explore the experience of transition to unsupervised, community-based exercise among men who had participated in a hospital-based supervised exercise programme in order to propose components that supported transition to unsupervised exercise. METHODS: Participants were selected by means of purposive, criteria-based sampling. Men undergoing androgen deprivation therapy who had completed a 12-week hospital-based, supervised, group exercise intervention were invited to participate. The programme involved aerobic and resistance training using machines and included a structured transition to a community-based fitness centre. Data were collected by means of semi-structured focus group interviews and analysed using thematic analysis. RESULTS: Five focus group interviews were conducted with a total of 29 men, of whom 25 reported to have continued to exercise at community-based facilities. Three thematic categories emerged: Development and practice of new skills; Establishing social relationships; and Familiarising with bodily well-being. These were combined into an overarching theme: From learning to doing. Components suggested to support transition were as follows: a structured transition involving supervised exercise sessions at a community-based facility; strategies to facilitate peer support; transferable tools including an individual exercise chart; and access to 'check-ups' by qualified exercise specialists. CONCLUSIONS: Hospital-based, supervised exercise provides a safe learning environment. Transferring to community-based exercise can be experienced as a confrontation with the real world and can be eased through securing a structured transition, having transferable tools, sustained peer support and monitoring.

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.

Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study.

OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) were enrolled in a prospective, randomized, controlled, non-blinded study conducted at 10 European centres. The BPH6 responder endpoint assessed symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation and safety. Additional evaluations of patient perspective, quality of life and sleep were prospectively collected, analysed and presented for the first time. RESULTS: Significant improvements in International Prostate Symptom Score (IPSS), IPSS quality of life (QoL), BPH Impact Index (BPHII), and maximum urinary flow rate (Qmax ) were observed in both arms throughout the 2-year follow up. Change in IPSS and Qmax in the TURP arm were superior to the PUL arm. Improvements in IPSS QoL and BPHII score were not statistically different between the study arms. PUL resulted in superior quality of recovery, ejaculatory function preservation and performance on the composite BPH6 index. Ejaculatory function bother scores did not change significantly in either treatment arm. TURP significantly compromised continence function at 2 weeks and 3 months. Only PUL resulted in statistically significant improvement in sleep. CONCLUSION: PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option.

Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer.

INTRODUCTION: Changes in sexual function other than erectile dysfunction are sparsely investigated after radiation therapy for prostate cancer. AIM: To investigate orgasmic dysfunction, urinary incontinence during sexual activity, changes in penile morphology, and sensory disturbances in the penis in patients with prostate cancer treated with external-beam radiation therapy (EBRT). METHODS: In February 2015, men treated with EBRT at our center 3 months to 5 years previously (N = 519) received a study-specific questionnaire. This was developed from purpose-built questions and validated tools including the Erection Hardness Scale. All patients had received a radiation dose of 78 Gy. Androgen deprivation therapy was administered according to disease characteristics. MAIN OUTCOME MEASURES: Outcome measurements were prevalence rates and predictors of these side effects as identified by multivariate logistic regression analyses. RESULTS: One hundred nine patients were eligible (sexually active and had completed androgen deprivation therapy) for inclusion. Twenty-four percent reported anorgasmia, 44% reported a decreased intensity of their orgasms, and 40% reported that the time it took to reach orgasm had increased. Eleven percent reported anejaculation. Fifteen percent reported orgasm-associated pain. Only 4% reported urinary incontinence during sexual activity. Subjective penile length loss in excess of 1 cm was reported by 42%. Twelve percent reported an altered curvature of their penis after EBRT. Six percent reported painful erections. Twenty-seven percent reported decreased sensitivity in the penis after EBRT, 2% reported a cold sensation, and 2% reported paresthesia. Increasing time since final treatment increased the risk of penile sensory disturbances (odds ratio = 1.05; P = .028). CONCLUSION: Orgasmic dysfunction, changes in penile morphology, and sensory disturbances in the penis are common side effects of ERBT. Patients should be properly informed of the occurrence of these side effects before deciding which treatment to pursue. Frey A, Pedersen C, Lindberg H, et al. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer. J Sex Med 2017;14:558-565.

Penile vibratory stimulation in the treatment of post-prostatectomy incontinence: a randomized pilot study.

AIMS: To examine penile vibratory stimulation (PVS) in the treatment of post-prostatectomy urinary incontinence (UI). METHODS: Patients with post-prostatectomy UI were included in a 12-week trial. A 24-hr pad test and a 72-hr voiding diary were collected at baseline. Participants were randomized to receive PVS for the first 6 weeks (group 1) or for the final 6 weeks (group 2) of the study. The primary outcome was the difference in leakage between groups 1 and 2 at 6 weeks as measured by changes in the pad test. The trial was registered at www.clinicaltrials.org (NCT01540656). RESULTS: Data from 31 men were available for analyses. The difference in the change on the pad test between the groups did not reach statistical significance at 6 weeks (P = 0.13) while the change in incontinence episodes between groups approached statistical significance (P = 0.052). However, there was a median reduction of -33 g (P = 0.021) on the pad test and a median reduction in daily incontinence episodes of -1 (P = 0.023) in group 1 at 6 weeks. At 12 weeks, group 2 had a median decrease on the pad test of -8 g (P = 0.10) and no change in incontinence episodes. A pooled analysis showed a decline on the pad test of -13.5 g (P = 0.004) after PVS. Small improvements were seen in subjective symptom scores and 58% stated to be satisfied with PVS. Self-limiting side effects were experienced by 15% of patients. CONCLUSIONS: PVS is feasible in the treatment of post-prostatectomy UI. Larger trials are needed to document the clinical efficacy.

Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy: a randomized, controlled trial.

OBJECTIVE: To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP). PATIENTS AND METHODS: The present study was conducted between July 2010 and March 2013 as a randomized prospective trial at two university hospitals. Eligible participants were continent men with an International Index of Erectile Function-5 (IIEF-5) score of at least 18, scheduled to undergo nerve-sparing RP. Patients were randomized to a PVS group or a control group. Patients in the PVS group were instructed in using a PVS device (FERTI CARE(®) vibrator). Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks. Participants were evaluated at 3, 6 and 12 months after surgery with the IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at http://clinicaltrials.gov/ (NCT01067261). RESULTS: Data from 68 patients were available for analyses (30 patients randomized to PVS and 38 patients randomized to the control group). The IIEF-5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance. At 12 months, 16/30 (53%) patients in the PVS group had reached an IIEF-5 score of at least 18, while this was the case for 12/38 (32%) patients in the control group (P = 0.07). There were no significant differences in the proportions of continent patients between groups at 3, 6 or 12 months. At 12 months 90% of the PVS patients were continent, while 94.7% of the control patients were continent (P = 0.46). CONCLUSION: The present study did not document a significant effect of PVS. However, the method proved to be acceptable for most patients and there was a trend towards better erectile function with PVS. More studies are needed to explore this possible effect further.

Neglected side effects after radical prostatectomy: a systematic review.

INTRODUCTION: A series of previously neglected sexually related side effects to radical prostatectomy (RP) has been identified over the recent years. These include orgasm-associated incontinence (OAI), urinary incontinence in relation to sexual stimulation (UISS), altered perception of orgasm, orgasm-associated pain (OAP), penile shortening (PS), and penile deformity. AIM: The aim of this article is to conduct a systematic review of the literature regarding the above-mentioned side effects. METHODS: A predefined search strategy was applied in a thorough search of Medline, Web of science, and the online Cochrane library. The PRISMA guidelines for systematic reviews were followed, and protocol as well as search strategies was registered at http://www.crd.york.ac.uk/Prospero/ (RN: CRD42012003165). MAIN OUTCOME MEASURE: The main outcome measure was incidence rates for the relevant side effects. RESULTS: A total of 43 articles were included. OAI and UISS are experienced by 20-93% of RP patients at least a few times after surgery. Although these issues are associated to postoperative daytime incontinence, previous transurethral resection of the prostate (TURP) is the only known predicting factor. Alterations of orgasmic function are experienced by approximately 80% after RP. Erectile dysfunction seems to play an important role in waning orgasmic function. OAP is only experienced by a subset of the patients with reported rates varying between 3% and 19%. Sparing of the tips of the seminal vesicles has been shown to double the risk of OAP. PS occurs in 15-68% of RP patients. Nerve sparing and preservation of erectile function may help preserve penile length. With regard to all side effects, studies indicate that they are reduced over time. CONCLUSIONS: The sexually related side effects summarized in this review are common after RP. Meanwhile, it is difficult to predict which patients are at risk. Daytime incontinence, previous TURP, a lack of nerve sparing, and erectile dysfunction are all associated with the above-mentioned sexually related side effects.

Prevalence and predicting factors for commonly neglected sexual side effects to radical prostatectomies: results from a cross-sectional questionnaire-based study.

INTRODUCTION: Altered perception of orgasm, orgasm-associated pain, penile sensory changes, urinary incontinence (UI) during sexual activity, penile shortening (PS), and penile deformity following radical prostatectomy (RP) have received increasing attention from researchers. AIM: The aim of this study is to describe the prevalence and predictors of the above-mentioned side effects. METHODS: This was a cross-sectional questionnaire-based study among men who had undergone RP between 3 and 36 months prior to study inclusion. Predicting factors were identified through logistic regression analyses. MAIN OUTCOME MEASURES: The primary outcome measures were prevalence rates of the above-mentioned side effects. RESULTS: Overall, 316 questionnaires were available for analyses. Of the sexually active patients (n = 256), 12 (5%) reported anorgasmia, whereas 153 (60%) reported decreased orgasm intensity. Delayed orgasms were reported by 146 (57%). Twenty-three patients (10%) had experienced pain during orgasm. UI during sexual activity were reported by 99 patients (38%). Out of the whole population, 77 patients (25%) reported sensory changes in the penis. A total of 143 patients (47%) reported a subjective loss of penile length of >1 cm. An altered curvature of the penis was reported by 30 patients (10%). Patients had increasing risk of UI during sexual activity (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.10-1.25) and orgasmic dysfunction (OR 1.09; 95% CI 1.01-1.16) with increasing International Consultation on Incontinence Questionnaire scores. Erectile dysfunction (OR 1.81; 95% CI 1.07-3.10) and a high body mass index (OR 1.10; 95% CI 1.02-1.19) increased the risk of PS after RP. Nerve-sparing (OR 0.32; 95% CI 0.16-0.95) reduced the risk of PS. CONCLUSIONS: Orgasm-associated problems, UI during sexual activity, penile sensory changes, PS, and penile deformity are common side effects to RP. Daytime UI, erectile dysfunction, and nerve-sparing status can help identify patients at risk.

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.

Serum Androgens as Predictive Biomarkers: Results From a Randomized Clinical Trial Comparing Enzalutamide and Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). MATERIALS AND METHODS: We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). RESULTS: Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. CONCLUSION: Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

Male fertility restoration: in vivo and in vitro stem cell-based strategies using cryopreserved testis tissue: a scoping review.

IMPORTANCE: Advances in the treatment of childhood cancer have significantly improved survival rates, with more than 80% of survivors reaching adulthood. However, gonadotoxic cancer treatments endanger future fertility, and prepubertal males have no option to preserve fertility by sperm cryopreservation. In addition, boys with cryptorchidism are at risk of compromised fertility in adulthood. OBJECTIVE: To investigate current evidence for male fertility restoration strategies, explore barriers to clinical implementation, and outline potential steps to overcome these barriers, a scoping review was conducted. This knowledge synthesis is particularly relevant for prepubertal male cancer survivors and boys with cryptorchidism. EVIDENCE REVIEW: The review was conducted after the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews criteria and previously published guidelines and examined studies using human testis tissue of prepubertal boys or healthy male adults. A literature search in PubMed was conducted, and 72 relevant studies were identified, including in vivo and in vitro approaches. FINDINGS: In vivo strategies, such as testis tissue engraftment and spermatogonial stem cell transplantation, hold promise for promoting cell survival and differentiation. Yet, complete spermatogenesis has not been achieved. In vitro approaches focus on the generation of male germ cells from direct germ cell maturation in various culture systems, alongside human induced pluripotent stem cells and embryonic stem cells. These approaches mark significant advancements in understanding and promoting spermatogenesis, but achieving fully functional spermatozoa in vitro remains a challenge. Barriers to clinical implementation include the risk of reintroducing malignant cells and introduction of epigenetic changes. CONCLUSION: Male fertility restoration is an area in rapid development. On the basis of the reviewed studies, the most promising and advanced strategy for restoring male fertility using cryopreserved testis tissue is direct testis tissue transplantation. RELEVANCE: This review identifies persistent barriers to the clinical implementation of male fertility restoration. However, direct transplantation of frozen-thawed testis tissue remains a promising strategy that is on the verge of clinical application.

Penile rehabilitation after radical prostatectomy: what the evidence really says.

The pathophysiology of erectile dysfunction after radical prostatectomy (RP) is believed to include neuropraxia, which leads to temporarily reduced oxygenation and subsequent structural changes in penile tissue. This results in veno-occlusive dysfunction, therefore, penile rehabilitation programmes focus on tissue oxygenation. Animal studies support the use of phosphodiesterase type 5 inhibitors (PDE5Is) after cavernous nerve damage but results from human studies are contradictory. The largest study to date found no long-term effect of either daily or on-demand PDE5I administration after RP compared with placebo. The effects of prostaglandin and vacuum erection devices are questionable and high-quality studies are lacking. Better documentation for current penile rehabilitation and/or better rehabilitation protocols are needed. One must be careful not to repeat the statement that penile rehabilitation improves erectile function after RP so many times that it becomes a truth even without the proper scientific backing.