A randomized, double-blind, solifenacin succinate versus placebo control, phase 4, multicenter study evaluating urinary continence after robotic assisted radical prostatectomy.

PURPOSE: Bladder dysfunction influences recovery of urinary continence after radical prostatectomy. We performed a multicenter, randomized, double-blind study evaluating solifenacin vs placebo on return to continence in patients who were still incontinent 7 to 21 days after catheter removal after robot-assisted radical prostatectomy. MATERIALS AND METHODS: A wireless personal digital assistant was given to patients the day of catheter removal. Encrypted answers were transmitted daily to dedicated servers. After a 7 to 21-day treatment-free washout period, patients requiring 2 to 10 pads per day for 7 consecutive days were randomized (1:1) to 5 mg solifenacin daily or placebo. The primary end point was time from first dose to continence defined as 0 pads per day or a dry security pad for 3 consecutive days. Secondary end points included proportion of patients continent at end of study, average change in pads per day number and quality of life assessments. RESULTS: A total of 1,086 screened patients recorded personal digital assistant information. Overall 640 patients were randomized to solifenacin vs placebo and 17 failed to take medication. There was no difference in time to continence (p=0.17). Continence was achieved by study end in 91 of 313 (29%) vs 66 of 309 (21%), respectively (p=0.04). Pads per day change from baseline was -3.2 and -2.9, respectively (p=0.03). Dry mouth was the only common adverse event seen in 6.1% and 0.6%, respectively. Constipation rates were similar. The overall rate of continence in the entire population from screening to end of study was 73%. CONCLUSIONS: There was no effect on primary outcome but some secondary end points benefited the solifenacin arm. The study provides level 1B clinical evidence for continence outcomes after robot-assisted radical prostatectomy.

Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study.

PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction. MATERIALS AND METHODS: This randomized, double-blind, placebo controlled, 12-week study (4-week run-in and 8-week treatment) randomized 145 men to placebo, 147 to avanafil 100 mg and 148 to avanafil 200 mg on demand. The primary efficacy variable was the per subject proportion of sexual attempts during the treatment period in which subjects achieved erection sufficient for vaginal penetration within approximately 15 minutes after dosing as measured by a stopwatch. The attempt had to enable successful completion of sexual intercourse according to SEP question 3. RESULTS: Significantly greater mean per subject percentages of successful intercourse attempts within approximately 15 minutes after dosing were observed for avanafil 100 mg (mean 25.9%, LS mean ± SE 24.7% ± 2.9%) and 200 mg (mean 29.1%, LS mean 28.2% ± 2.9%) vs placebo (mean 14.9%, LS mean 13.8% ± 2.9%, p = 0.001 and <0.001, respectively). After treatment we noted a statistically significant difference between avanafil and placebo in the average per subject proportion of successful intercourse attempts according to SEP question 3 as early as 10 minutes in the 200 mg group and 12 minutes in the 100 mg group. Treatment emergent adverse events included headache, upper respiratory tract infection and nasal congestion, and most such events were mild or moderate in severity. CONCLUSIONS: Avanafil was efficacious within approximately 15 minutes of dosing compared to placebo. A statistically significant treatment difference in the percentage of successful sexual attempts was demonstrated as early as 10 minutes after treatment.

Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial.

BACKGROUND: Prostate cancer (PCa) patients with pathogenic/likely pathogenic germline variants (PGVs) in cancer predisposition genes may be eligible for U.S. Food and Drug Administration-approved targeted therapies, clinical trials, or enhanced screening. Studies suggest that eligible patients are missing genetics-informed care due to restrictive testing criteria. OBJECTIVE: To establish the prevalence of actionable PGVs among prospectively accrued, unselected PCa patients, stratified by their guideline eligibility. DESIGN, SETTING, AND PARTICIPANTS: Consecutive, unselected PCa patients were enrolled at 15 sites in the USA from October 2019 to August 2021, and had multigene cancer panel testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correlates between the prevalence of PGVs and clinician-reported demographic and clinical characteristics were examined. RESULTS AND LIMITATIONS: Among 958 patients (median [quartiles] age at diagnosis 65 [60, 71] yr), 627 (65%) had low- or intermediate-risk disease (grade group 1, 2, or 3). A total of 77 PGVs in 17 genes were identified in 74 patients (7.7%, 95% confidence interval [CI] 6.2-9.6%). No significant difference was found in the prevalence of PGVs among patients who met the 2019 National Comprehensive Cancer Network Prostate criteria (8.8%, 43/486, 95% CI 6.6-12%) versus those who did not (6.6%, 31/472, 95% CI 4.6-9.2%; odds ratio 1.38, 95% CI 0.85-2.23), indicating that these criteria would miss 42% of patients (31/74, 95% CI 31-53%) with PGVs. The criteria were less effective at predicting PGVs in patients from under-represented populations. Most PGVs (81%, 60/74) were potentially clinically actionable. Limitations include the inability to stratify analyses based on individual ethnicity due to low numbers of non-White patients with PGVs. CONCLUSIONS: Our results indicate that almost half of PCa patients with PGVs are missed by current testing guidelines. Comprehensive germline genetic testing should be offered to all patients with PCa. PATIENT SUMMARY: One in 13 patients with prostate cancer carries an inherited variant that may be actionable for the patient's current care or prevention of future cancer, and could benefit from expanded testing criteria.

Low-Intensity Shockwave Therapy in the Treatment of Erectile Dysfunction.

Introduction Low-intensity shockwave therapy (LISWT) may improve erectile function in patients with mild to moderate erectile dysfunction (ED). Currently there is a paucity of research and prospective data on the utilization of LISWT in patients with ED. We present the results of our phase II clinical trial of LISWT with short-term follow-up in a cohort of patients with mild to moderate vasculogenic ED. Methods We obtained IRB approval and prospectively enrolled patients with mild to moderate vasculogenic ED. Baseline International Index of Erectile Function (IIEF) scores and peak systolic velocities (PSV) of cavernosal arteries measured on duplex penile ultrasound were obtained prior to treatment. Treatment included 6600 total shocks per session, for a total of six consecutive weekly treatment sessions. Baseline Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were obtained at the completion of the treatment course. IIEF, EDITS and PSV were evaluated again at one-month follow-up. Clinical significance was defined as a median IIEF score increase of four points from baseline or an EDITS total score increase to greater than 65 or increase of greater than ten from baseline. Treatment success was evaluated on an individual basis and defined by a clinically significant improvement in questionnaire score. Results A total of 25 patients were enrolled in the trial, with 22 patients reporting for one-month follow-up. 68% (15/22) of patients demonstrated treatment success. In the cohort there was improvement in median EDITS from 61 (IQR 49-92) to 73 (IQR 43-49), which did meet criteria for clinical significance, but did not reach statistical significance (p = 0.74). IIEF improved from a median of 13 (IQR 12-19) to 18 (IQR 14-25), which did reach statistical significance (p = 0.011). On duplex ultrasound, mean cavernosal artery PSV increased from 34.3 cm/s (IQR 25.7-51.1) to 38.0 cm/s (IQR 31.6-45.1); however, these differences were statistically insignificant (p = 0.986). Of the 25 patients undergoing LISWT, two reported discomfort during treatment sessions, which subsided after repositioning the device without alterations in energy delivered. Conclusion LISWT may be a safe and potentially efficacious clinical modality for treatment of patients with mild to moderate vasculogenic ED demonstrating increases in cavernosal artery PSV and improvements in IIEF and EDITS scores in short-term follow-up. Longitudinal studies with increased power are needed to better evaluate the long-term efficacy and cost-efficiency of this therapy.

Male-to-Female Gender Reassignment Surgery: An Institutional Analysis of Outcomes, Short-term Complications, and Risk Factors for 240 Patients Undergoing Penile-Inversion Vaginoplasty.

OBJECTIVE: To report outcomes, complications, and risk factors of a population cohort undergoing male-to-female gender affirmation surgery via penile-inversion vaginoplasty by a single surgeon at a large academic institution. As gender dysphoria awareness increases among the medical community, so does the population of patients seeking gender-affirmation surgery. MATERIALS AND METHODS: A prospectively maintained database of patients undergoing penile-inversion vaginoplasty was retrospectively queried for all available patients with at least 1 week of postoperative follow-up. Univariate and multivariate analyses were performed using Fisher's exact test and logistic regression, respectively, in order to evaluate relationship of risk factors to complications at 30, 60, and 90 days, as well as the likelihood of revision/reoperation. RESULTS: From November 2016 to April 2018, 240 penile-inversion vaginoplasties were performed. Median follow-up was 87 days. When accounting for competing risk factors, only noncompliance with postoperative dilation regimen and activity restriction was significantly associated with increased risk of complications or reoperation/revision. Overall incidence of reoperation/revision was 7.9% (n = 19). Reasons for reoperation included cosmesis (3.8%; n = 9), neovaginal stenosis (2.1%; n = 5), and wound dehiscence (0.8%; n = 2), with less than 0.5% (n = 1) reoperations for meatal stenosis, hematoma or rectovaginal fistula, respectively. Incidence of Clavien IIIa-b complications was 1.7% (n = 4). There were no Clavien IV-V complications. CONCLUSION: At short-term follow-up, gender-affirmation surgery is associated with low rates of reoperation and revision and few major complications when performed by an experienced, high-volume surgeon. Patient selection and compliance is imperative. Increased reporting among surgeons is necessary to continue to improve patient outcomes.

A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer.

PURPOSE: Imiquimod is a toll-like receptor agonist with proven antitumor activity as a topical treatment for skin cancer. TMX-101 (Vesimune) is a novel liquid formulation of imiquimod optimized for intravesical delivery. The agent demonstrated safety as an intravesical treatment for non-muscle-invasive bladder cancer in a phase 1 clinical trial. We report the results of a phase 2 prospective multicenter clinical trial assessing the safety and activity of TMX-101. MATERIALS AND METHODS: Patients with non-muscle-invasive bladder cancer containing carcinoma in situ were eligible for inclusion. Enrolled patients received 6 weekly intravesical administrations of 200mg/50ml TMX-101 0.4%. End points included rate of adverse events, changes in urinary cytokine levels following treatment, and clinical response at 6 weeks following final instillation, defined as negative posttreatment bladder biopsy and urine cytology results. RESULTS: A total of 12 patients were enrolled, with 10 available for efficacy analysis. Half of the patients (6/12) had received≥2 prior induction courses of bacillus Calmette-Guerin. All patients received all 6 doses of TMX-101 per protocol. Overall, 75% of patients experienced treatment-related adverse events, only 1 of which was>grade 2 (urinary tract infection). Furthermore, 2 patients demonstrated a negative cytology and biopsy result at 6 weeks following treatment. Significant increases in urinary cytokines, including IL-6 and IL-18, were seen following treatment. CONCLUSION: In this phase 2 pilot study in patients with carcinoma in situ bladder cancer, intravesical TMX-101 was safe and well tolerated with common, mild genitourinary adverse effects. Clinical activity was suggested by the increase in posttreatment urinary cytokines. Complete responders were seen. Further investigation of the agent is warranted.

Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus.

OBJECTIVE: To prospectively assess the safety and effectiveness of the investigational phosphodiesterase 5 inhibitor avanafil to treat erectile dysfunction in men with diabetes mellitus. PATIENTS AND METHODS: This 12-week, multicenter, double-blind, placebo-controlled study conducted between December 15, 2008, and February 11, 2010, randomized 390 men with diabetes and erectile dysfunction 1:1:1 to receive avanafil, 100 mg (n=129), avanafil, 200 mg (n=131), or placebo (n=130). Coprimary end points assessed changes in the percentage of sexual attempts in which men were able to maintain an erection of sufficient duration to have successful intercourse (Sexual Encounter Profile [SEP] 3), percentage of sexual attempts in which men were able to insert the penis into the partner's vagina (SEP 2), and International Index of Erectile Function erectile function domain score. RESULTS: Compared with placebo, least-squares mean change from baseline to study end in SEP 3, SEP 2, and International Index of Erectile Function erectile function domain score were significantly improved with both avanafil, 100 mg (P≤.002), and avanafil, 200 mg (P<.001). Additional analyses indicated that successful intercourse could be initiated in 15 minutes or less through more than 6 hours after avanafil dosing. Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion. CONCLUSION: Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing. The adverse events seen with avanafil were similar to those seen with other phosphodiesterase 5 inhibitors. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00809471.