Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

The International Penile Prosthesis Implant Consensus Forum: clinical recommendations and surgical principles on the inflatable 3-piece penile prosthesis implant.

Despite significant scientific advances in the modern three-piece inflatable penile prosthesis implant surgery, it is not without surgical risks and can carry additional cosmetic and psychosocial consequences in poorly selected and consented individuals. To address this problem, an international group of key opinion leaders and high-volume prosthetic surgeons reviewed the current guidelines and clinical evidence, discussed their experiences, and formed a consensus regarding inflatable penile prosthesis surgery. The findings of this consensus panel were presented at the 17th biennial Asia Pacific Society of Sexual Medicine scientific meeting. The experts concluded that proper patient selection, informed consent and strict adherence to safe surgical principles are important to optimize clinical outcomes. Furthermore, most intraoperative complications, if recognized, can be addressed intraoperatively to enable placement of the device at the time of initial surgery. Men with significant corporal fibrosis due to Peyronie's disease, prior prosthesis explantation and priapism, and men who have undergone construction of a neophallus, as well as men who receive concurrent continence surgery, are complex cases requiring additional care and advanced techniques to obtain optimal surgical outcomes. Variability in patient care - in terms of postoperative antibiotic use, pain management, scrotal care, and cycling of the penile prosthesis implant - must be reduced to enable optimization and assessment of outcomes across patient groups.

Indications for Penile Prosthesis Revision: Lessons Learned to Limit Technical Causes of Reoperation.

INTRODUCTION: Reoperations are necessary in approximately 30% of penile prostheses over 15 years following original implantation. AIM: To determine the most common indications for initial penile prosthesis reoperation at our institution and to describe technical alterations that have improved postoperative outcomes. METHODS: A retrospective review of all patients who underwent penile prosthesis reoperation surgery at a single, high-volume Canadian center between 2006 and 2018 was performed. Patient demographic information, prosthetic device factors, and surgical complications were analyzed. MAIN OUTCOME MEASURE: The primary outcomes were the indications for and variables associated with initial penile prosthesis reoperation. RESULTS: During the study period, 99 first-time penile prosthesis reoperations were performed out of 1,161 penile prosthesis procedures (Figure 1). This included 14 (14.1%) explants, 32 (32.3%) revisions, and 53 (53.5%) explant and reimplants. Indications for reoperation included 49 (49.5%) mechanical failures, 28 (28.3%) technical causes (such as correction of malposition or device herniation), and 12 (12.1%) procedures to treat chronic postoperative pain. Median follow-up was 78.5 months, and median time to reoperation was 46 months. Mechanical failures commonly occurred in the tubing (n = 13, 26.5%) and cylinders (n = 13, 26.5%). The most frequently repositioned component was the valve pump (n = 11, 39.3%). Infection-related indications for reoperation were uncommon (n = 10, 10.1%). CLINICAL IMPLICATIONS: More than a quarter of penile prosthesis reoperations may have been preventable with alterations in surgical technique, device positioning, and postoperative care. STRENGTHS AND LIMITATIONS: This study evaluates a range of indications for initial penile prosthesis reoperation performed by a high-volume single surgeon over a 12-year period. Limitations include the retrospective nature of the study, loss of patients to follow-up, and lack of etiological determinants of prosthesis failure. CONCLUSIONS: Reoperation for device repositioning and herniation was required for more than a quarter of the initial penile prosthesis implants. Modifications in surgical technique and perioperative care can help reduce the incidence of these technical causes for reoperation. Chan EP, Punjani N, Campbell JD, et al. Indications for Penile Prosthesis Revision: Lessons Learned to Limit Technical Causes of Reoperation. J Sex Med 2019; 16:1444-1450.

Hydro-Jet Dissection of the Cavernous Nerves Preserves Erection Function in a Radical Prostatectomy Animal Model.

BACKGROUND: Postoperative erectile dysfunction (ED) remains a prevalent consequence of radical prostatectomy (RP) that significantly impacts patient quality of life. Water-jet technology is widely used for dissection in neurosurgical procedures but novel to urologic surgery. AIM: To establish the impact of hydro-jet dissection (HJD) of the cavernous nerves (CN) on postoperative erectile function in an animal model of RP-induced ED. METHODS: 32 male Sprague-Dawley rats were randomized to 4 groups: Sham surgery (n = 8), bilateral HJD of CN (n = 8), blunt CN injury (n = 8), or stretch CN injury (n = 8). After 4 weeks, erectile function was assessed by measuring intracavernous pressure (ICP), and penile tissues were harvested for immunohistologic studies. MAIN OUTCOME MEASURE: The peak ICP and the area under the curve were calculated for each group. Immunohistologic studies were performed for α-smooth muscle actin and neuronal nitric oxide synthase on cross-sections of penile tissue. RESULTS: Rats in the HJD group demonstrate a significantly higher mean peak ICP and area under the curve compared with both CN injury groups (P = .001). Postoperative erectile function in the HJD group returned to baseline function. Preservation of α-smooth muscle actin and neuronal nitric oxide synthase was observed in the HJD group compared with the other surgical trauma groups. CLINICAL IMPLICATIONS: Hydro-jet dissection used in an RP animal model maintains erectile function and offers a potential benefit that warrants further human studies. STRENGTHS & LIMITATIONS: This is a novel animal study comparing a new technology to established CN dissection techniques. This study uses an animal model, which may not completely translate to post-RP ED in humans. CONCLUSION: Hydro-jet dissection of the CN during RP in an animal model is associated with significantly better postoperative erectile function when compared with other CN injury. Clinical studies are needed to further investigate the putative benefit of HJD on erectile function in patients undergoing RP. Campbell JD, Alenezi H, DeYoung LX, et al. Hydrojet Dissection of the Cavernous Nerves Preserves Erection Function in a Radical Prostatectomy Animal Model. Sex Med 2019;7:104-110.

Canadian consensus algorithm for erectile rehabilitation following prostate cancer treatment.

INTRODUCTION: The present descriptive analysis carried out by a pan-Canadian panel of expert healthcare practitioners (HCPs) summarizes best practices for erectile rehabilitation following prostate cancer (PCa) treatment. This algorithm was designed to support an online sexual health and rehabilitation e-clinic (SHARe-Clinic), which provides biomedical guidance and supportive care to Canadian men recovering from PCa treatment. The implications of the algorithm may be used inform clinical practice in community settings. METHODS: Men's sexual health experts convened for the TrueNTH Sexual Health and Rehabilitation Initiative Consensus Meeting to address concerns regarding erectile dysfunction (ED) therapy and management following treatment for PCa. The meeting brought together experts from across Canada for a discussion of current practices, latest evidence-based literature review, and patient interviews. RESULTS: An algorithm for ED treatment following PCa treatment is presented that accounts for treatment received (surgery or radiation), degree of nerve-sparing, and level of pro-erectile treatment invasiveness based on patient and partner values. This algorithm provides an approach from both a biomedical and psychosocial focus that is tailored to the patient/partner presentation. Regular sexual activity is recommended, and the importance of partner involvement in the treatment decision-making process is highlighted, including the management of partner sexual concerns. CONCLUSIONS: The algorithm proposed by expert consensus considers important factors like the type of PCa treatment, the timeline of erectile recovery, and patient values, with the goal of becoming a nationwide standard for erectile rehabilitation following PCa treatment.

Multi-institutional Prospective Analysis of Intralesional Injection of Collagenase Clostridium Histolyticum, Tunical Plication, and Partial Plaque Excision and Grafting for the Management of Peyronie's Disease.

OBJECTIVE: To compare in a prospective nonrandomized fashion, the outcomes of collagenase clostridium histolyticum (CCH) and surgical interventions (tunical plication [TP] and partial plaque excision and grafting [PEG]) in patients with Peyronie's disease (PD). Intralesional injection of CCH is the only Food and Drug Administration-approved nonsurgical intervention for PD. MATERIALS AND METHODS: Between June 2015 and January 2017, 57 patients with PD and dorsal, dorsolateral, and/or lateral penile curvatures 30°-90° were included in this study. Patients with ventral curvature, hourglass deformity, and previous surgery for PD were excluded. All patients completed questionnaires and underwent penile measurements and penile vascular studies prior to and after completion of treatment, and were followed for at least 6 months. RESULTS: CCH was administered to 18 patients, TP performed in 14, and PEG in 25. The median follow-up for the whole cohort was 12 months (6-28). Mean changes in curvature after treatment were 23.3° (34.4%) for CCH, 72.0° (92.2%) for TP, and 71.8 ° (94.9%) for PEG, P<.001. Mean changes in International Index of Erectile Function-5 scores were +5.7 for CCH, +4.9 for TP, and +2.2 for PEG, P = .395. Mean penile length changes were -0.2 cm for CCH, -1.0 cm for TP, and +0.9 cm for PEG, P<.001. Three patients in the CCH group had bothersome residual curvature and underwent uneventful TP. CONCLUSION: Surgical options are associated with superior curvature correction. CCH is an effective and safe option for motivated patients who prefer to avoid surgery. PEG is associated with a small stretched penile length gain.

Characterization of Septal and Punctate Scarring in Peyronie's Disease.

OBJECTIVE: To characterize patients with isolated septal scarring (ISS) and punctate scarring (PS) in Peyronie's disease (PD) and to highlight the importance of duplex ultrasonography in the workup of patients with PD. MATERIALS AND METHODS: Data from all men undergoing duplex ultrasonography at London Health Sciences Center for PD or erectile dysfunction over a 3-year period were retrospectively reviewed. RESULTS: Our cohort included 722 patients with duplex ultrasound. ISS were demonstrated in 217 patients (30%), and PS in 197 (27%), with 72 (33%) and 148 (75%), respectively, having a normal physical examination. In both ISS and PS groups, more than half of patients also had associated erectile dysfunction. Predictive factors for ISS on multivariate analysis included trauma history (odds ratio [OR] 1.90, P = .04) and age (OR 1.02, P = .01). Patients with ISS were more likely to have dorsal curvature (OR 3.81, P <.01). CONCLUSION: Limited data exist in the literature regarding ISS and PS in PD. Our study illustrates that one-third of ISS and three-quarters of PS would have remained unrecognized without duplex ultrasonography, and it highlights its importance in the workup and subsequent management of these patients. Further studies are needed to better understand and to determine the at-risk patient and the associated clinical implications of ISS and PS, and to ultimately provide optimized and individualized management strategies.

A Worldwide Survey on Peyronie's Disease Surgical Practice Patterns Among Surgeons.

BACKGROUND: Despite published guidelines on Peyronie's disease (PD), there are limited data on actual surgical practice among surgeons. AIM: To evaluate the surgical practice patterns in PD among surgeons from different continents and members of various sexual medicine societies. METHODS: An anonymous survey on various pre-, intra-, and postoperative aspects of PD surgical care was distributed in printed format during International Society of Sexual Medicine meetings and as an online survey to International Society of Sexual Medicine members. OUTCOMES: 390 surgeons responded to the survey, with great variations in pre-, intra-, and postoperative strategies in PD surgical care. RESULTS: Most surgeons performed fewer than 10 penile plications and 10 graft surgeries per year. Modified Nesbit plication was the preferred option by most surgeons. Surgeons who received fellowship training were more likely to perform autologous than allograft surgery (odds ratio = 1.79, 95% CI = 1.13-2.82, P = .01). The use of penile color duplex ultrasound was inconsistently performed, with higher-volume surgeons (ie, >20 cases operated a year) more likely to use this diagnostic modality (odds ratio = 70.18, 95% CI = 20.99-234.6, P < .001). Most surgeons agreed that surgical intervention should be performed only after a 6-month history of stable penile curvature, although higher-volume surgeons were more inclined to perform surgery sooner (P = .08). CLINICAL IMPLICATIONS: Although it is unknown whether variations in PD surgery significantly affect clinical outcome and patient satisfaction rate, this worldwide survey study has the potential to assist in the formation of a new practice guideline and serve as the basis for future prospective multinational studies. STRENGTH AND LIMITATIONS: This is one of the largest surveys on PD practice and, to our knowledge, the only survey conducted across various sexual medicine societies, with the inclusion of many high-volume and experienced PD surgeons. This also is the 1st study to comprehensively evaluate many key aspects in surgical practice patterns for PD. However, the categorization on the questionnaire used in this survey was not designed to allow for direct comparison given the possibility of some surgeons with dual society memberships, reporting biases, large CIs in outcomes, different patient demographics, and cultural acceptance. CONCLUSION: There is great variation in surgical practice patterns in PD management, including key differences among surgeons across different continents and sexual medicine societies. Chung E, Wang R, Ralph D, et al. A Worldwide Survey on Peyronie's Disease Surgical Practice Patterns Among Surgeons. J Sex Med 2018;15:568-575.

EFFICACY AND SAFETY OF A NEW TOPICAL TESTOSTERONE REPLACEMENT GEL THERAPY FOR THE TREATMENT OF MALE HYPOGONADISM.

OBJECTIVE: Testosterone replacement therapy is indicated for male hypogonadism. This study aimed to evaluate the efficacy and safety of testosterone gel 2% (Tgel) over 90 days. METHODS: This phase 3, open-label, noncomparator study was conducted in adult hypogonadal men (2 consecutive fasting serum testosterone values <300 ng/dL and >86% subjects with symptoms consistent with testosterone deficiency). Subjects applied Tgel 23 mg/day (single pump-actuation using a hands-free cap applicator). The dose was uptitrated to 46 mg/day after 2 weeks if the 4-hour serum total testosterone level was <500 ng/dL. The dose could be further up- or downtitrated to 23, 46, and 69 mg on Days 21, 42, and 63. The primary endpoint included the percentage of subjects with average testosterone concentration (Cave (0-24)) between 300 and 1,050 ng/dL on Day 90. Safety endpoints were adverse events (AEs), laboratory parameters, and vital signs. RESULTS: Of the 159 who enrolled, 139 men completed the study. Approximately three-quarters (76.1%) of subjects met Cave criteria on Day 90. Most AEs were mild to moderate. There were 5 serious AEs, and 1 (myocardial infarction) was judged as possibly related to Tgel. Confirmed excessive increases in prostate-specific antigen or hematocrit levels were rare. Tgel had a favorable local skin tolerability profile. CONCLUSION: Overall, 76% of subjects achieved Cave between 300 and 1,050 ng/dL with Tgel. Symptoms of testosterone deficiency improved with few safety concerns. ABBREVIATIONS: AE = adverse event Cave(0-24) = average testosterone concentration CI = confidence interval Cmax = maximum concentration IIEF = International Index of Erectile Function MAF = Multidimensional Assessment of Fatigue PK = pharmacokinetic PSA = prostate-specific antigen SAE = serious adverse event SF-12 = Short Form 12 Health Survey Tgel = testosterone gel 2% Tmax = time to achieve maximum concentration TRT = testosterone replacement therapy.

Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results from a Randomized Controlled Trial (REACTT).

INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery, which was predefined as achieving an International Index of Erectile Function (IIEF)-EF score ≥22. Here, we report descriptive post-hoc analyses, using the more strict definition for EF-recovery of returning back to the pre-surgery IIEF-EF-level ("back-to-baseline analysis"). METHODS: REACTT included 422 men <68 years with adenocarcinoma of the prostate and preoperative IIEF-EF ≥22 who underwent nsRP at 50 centers from 9 European countries and Canada. Patients were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open-label tadalafil OaD treatment (OLT). MAIN OUTCOME MEASURES: Proportion of patients returning to their preoperative IIEF-EF category (22-25 or ≥26) at the end of DBT, DFW, and OLT. RESULTS: Overall, 92.4% of patients had pre-surgery (baseline) IIEF-EF scores ≥26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%), 7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and 7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1 PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group difference at the end of DBT was not maintained after DFW. After 3 months of OLT with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF had almost doubled in all 3 groups. CONCLUSION: Changing the definition for EF-recovery from IIEF-EF ≥22 to the more strict definition of "returning back-to-baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP improved drug-assisted EF, but had no effect on unassisted EF following treatment cessation after 9 months.

Impact of Baseline Total Testosterone Level on Successful Treatment of Sexual Dysfunction in Men Taking Once-Daily Tadalafil 5 mg for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: An Integrated Analysis of Three Randomized Controlled Trials.

INTRODUCTION: Controversy exists as to whether erectile response to phosphodiesterase type 5 inhibitors is compromised in men with low total testosterone (TT) levels. This is amplified by reports of improved response to phosphodiesterase type 5 inhibitor therapy after coadministration of testosterone replacement therapy in hypogonadal men unresponsive to phosphodiesterase type 5 inhibitors. AIM: To determine whether TT and luteinizing hormone levels influence efficacy of tadalafil for erectile dysfunction in men with concomitant lower urinary tract symptoms and benign prostatic hyperplasia. METHODS: This integrated analysis included 1,075 men randomized to once-daily tadalafil 5 mg (n = 540) or placebo (n = 535) for 12 weeks in three prospective clinical trials who had not received concomitant testosterone replacement therapy. Subjects were categorized at baseline by low vs normal TT levels (n = 1,049; <300 vs ≥300 ng/dL) and normal vs high luteinizing hormone levels (n = 1,058; ≤9.4 vs >9.4 mIU/mL). Treatment-group differences in International Index of Erectile Function (IIEF) by hormone subgroups were assessed using analysis of covariance. MAIN OUTCOME MEASURES: Changes in IIEF erectile function domain and other domain scores. RESULTS: The overall study population was comprised primarily of white men (>86%) with a mean age range of 64 to 70 years. Median baseline TT level in the integrated population was 355 ng/dL; levels were lower than 300 ng/dL (cutoff for normal) in 32.4% of men. Men with low TT levels reported diabetes (21.8%), cardiovascular disease (54.1%), and hypertension (49.1%) numerically more often than men with normal TT levels (10.6%, 43.2%, and 36.7%, respectively). Low TT and high luteinizing hormone levels were associated with numerically, but not statistically significantly, lower 12-week IIEF domain scores compared with those with normal levels. Changes in most 12-week IIEF domain scores showed that tadalafil was significantly more effective than placebo (P < .02). CONCLUSION: Low TT levels at baseline did not negatively influence response to tadalafil in men of advancing age with concomitant lower urinary tract symptoms and benign prostatic hyperplasia and erectile dysfunction.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

BACKGROUND: Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. OBJECTIVE: To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. INTERVENTION: Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. RESULTS AND LIMITATIONS: The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. CONCLUSIONS: Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. PATIENT SUMMARY: Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01026818.

Tadalafil therapy for erectile dysfunction following prostatectomy.

Erectile dysfunction is a major complication affecting the quality of life of patients and partners after radical prostatectomy. Evolving evidence suggests that early penile rehabilitation may provide better erectile function after surgery. Phosphodiesterase type 5 (PDE-5) inhibitors are routinely considered a first-line treatment option in most algorithms for penile rehabilitation owing to their efficacy, ease of use, wide availability and minimal morbidity. Tadalafil is a long-acting, potent PDE-5 inhibitor for erectile dysfunction, with demonstrated effect in animal studies at preserving penile smooth muscle content and prevention of fibrosis of cavernosal tissue. This article evaluates the existing literature on tadalafil and critically analyzes its impact on erectile function following radical prostatectomy.

Proportion of tadalafil-treated patients with clinically meaningful improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia ­ integrated data from 1,499 study participants.

OBJECTIVES: To evaluate the proportion of patients achieving clinically meaningful improvement of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) with tadalafil using two definitions of response. PATIENTS AND METHODS: Post hoc integrated analysis of four placebo-controlled studies in men (aged ≥45 years; International Prostate Symptom Score [IPSS] of ≥13; maximum urinary flow rate [Q(max)] of ≥4 to ≤15 mL/s) with BPH-LUTS randomised to tadalafil 5 mg (752 patients) or placebo (747) for 12 weeks after a 4-week placebo run-in. Responders were defined as having a total IPSS improvement of ≥3 points or ≥25% from randomisation to endpoint (Week 12). Response status was calculated per patient, and relative benefit and odds ratio (OR) with 95% confidence interval (CI) of tadalafil vs placebo was calculated using a logistic Generalised Mixed Model for Repeated Measures. RESULTS: Tadalafil 5 mg once daily resulted in a significantly greater proportion of patients achieving a ≥3-point IPSS improvement (71.1% and 56.0% for tadalafil and placebo patients, respectively [OR 1.9, 95% CI 1.5, 2.4; P < 0.001]) and achieving a ≥25% improvement in total IPSS randomisation to endpoint (61.7% and 45.5% for tadalafil and placebo patients, respectively [OR 2.0, 95% CI 1.6, 2.5; P < 0.001]). CONCLUSION: About two-thirds of tadalafil-treated patients achieve a clinically meaningful improvement in BPH-LUTS symptoms, based on two different definitions of responder status.

Pharmacologic and surgical therapies for sexual dysfunction in male cancer survivors.

The recent recognition that many men experience sexual dysfunction following their diagnosis and treatment of genitourinary cancers, has led to the development multiple varied strategies that attempt to restore or preserve that function. In this manuscript we review the understanding of why it happens, highlight novel management strategies and discuss the concept of penile rehabilitation (PR) following prostate cancer (PCa) treatment, glans preserving strategies among men diagnosed with penile cancer and address the controversial issue of testosterone therapy in men with PCa.

Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting.

INTRODUCTION: Optimal oncologic control of higher stage prostate cancers often requires sacrificing the neurovascular bundles (NVB) with subsequent postoperative erectile dysfunction (ED), which can be treated with interposition graft using sural nerve. AIMS: To examine the long term outcome of sural nerve grafting (SNG) during radical retropubic prostatectomy (RRP) performed by a single surgeon. METHODS: Sixty-six patients with clinically localized prostate cancer and preoperative International Index of Erectile Function (IIEF) score >20 who underwent RRP were included. NVB excision was performed if the risk of side-specific extra-capsular extension (ECE) was >25% on Ohori' nomogram. SNG was harvested by a plastic surgeon, contemporaneously as the urologic surgeon was performing RRP. IIEF questionnaire was used pre- and postoperatively and at follow-up. MAIN OUTCOME MEASURES: Postoperative IIEF score at three years of men undergoing RRP with SNG. Recovery of potency was defined as postoperative IIEF-EF domain score >22. RESULTS: There were 43 (65%) unilateral SNG and 23 (35%) bilateral SNG. Mean surgical time was 164 minutes (71 to 221 minutes).The mean preoperative IIEF score was 23.4+1.6. With a mean follow-up of 35 months, 19 (28.8%) patients had IIEF score >22. The IIEF-EF scores for those who had unilateral SNG and bilateral SNG were 12.9+4.9 and 14.8+5.3 respectively. History of diabetes (P=0.001) and age (P=0.007) negatively correlated with recovery of EF. 60% patients used PDE5i and showed a significantly higher EF recovery (43% vs. 17%, P=0.009). CONCLUSIONS: SNG can potentially improve EF recovery for potent men with higher stage prostate cancer undergoing RP. The contemporaneous, multidisciplinary approach provides a good quality graft and expedited the procedure without interrupting the work-flow.