Trost, L

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We sought to evaluate outcomes of a novel protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Objective To evaluate whether additional rounds of CCH using a novel protocol in men previously unresponsive results in greater curve improvements. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men were randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes were compared between treatment and control groups. Key measures included objective curve improvements and standardized/non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 38/40 men have been randomized to date, with 22 having fully completed treatment. Mean age was 57 years, with a median PD duration of 22 months. Median composite baseline curvature was 65 degrees, with 40% having hourglass or indentation deformities, 8% calcification, median baseline IIEF-EFD 20, and 58% able to have penetrative intercourse. Median estimated improvement with the prior CCH series was 0% (IQR 0, 18.8), and the median number of prior injections was 8. The majority of men were dissatisfied with their prior series of CCH (58% vs 35% satisfied, 8% neutral). Of the 22 men who had completed the study protocol, 50% required 1 series, 14% 2 series, 29% 3 series, and 7% 4 series. Compared to the no treatment arm, treated men experienced significantly greater improvements (median 60 degrees vs 0, p = 0.01). IIEF-EFD was non-statistically higher in treated men (0 vs -5, p = 0.17). 92% of men reported a subjective major improvement in curvature, with the median subjectively estimated improvement 90%. 42% reported improved sensitivity (58% no change), while 63% reported improved or no change in erectile function, with 9% unsure, and 27% worse. Post-treatment, 92% of men were very satisfied with CCH as a treatment and 8% neutral. Conclusions Repeating CCH using a novel protocol after an initially unsuccessful course of CCH achieves significant improvements in curvature and patient satisfaction. Additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: PathRight Medical.

ABSTRACT Introduction Covid-19 has helped drive all forms of medicine away from traditional brick and mortar medical interactions. Given the availability of online services to obtain treatments for ED, we developed a website to facilitate patient education, triage and men's health appointment scheduling. Objective We sought to assess characteristics of men who utilized a novel website to treat their ED. Methods We report on 50 patients who ultimately booked and attended appointments (video or in person) for erectile dysfunction. Patients found our website through our institution's main informational ED pages or through youtube links from our men's health video playlist library. Patients create an institutional account and are then asked a series of MD created questions designed to streamline patient triage and complete the majority of chart documentation ahead of the appointment. Patients are then sent videos relevant to their condition and future appointment options. Results 2300 users investigated the ED portion of the website with 1.8% of patients ultimately following through with an appointment. 13% of patients who explored the ED portion of the site created a user account that allows a questionnaire to be taken. 90% of men who began the ED questionnaire completed with a mean time of 11 minutes. 52% of men offered an appointment based on their responses completed the patient scheduling form. 71% of traffic was on mobile devices with 29% on desktop/tablet. Site use by time of day is shown in figure 1. Mean age of patients was 53. 92% of patients had ED that occurred > 6 months. Mean SHIM score was 8.2 (IQR 4-12). 80% of participants had both desire and opportunity for sexual activity, 20% did not meet both criteria and thus SHIM scores were less valid for these men. Of the users 28% had never tried pde5s, 32% had partial success with pde5s, 24% could not tolerate or afford pde5s and 42% had unsatisfactory results with pde5s. PDE5 naïve patients were seen by an internal medicine MD specializing in men's health, 10 were seen by surgeons as they requested IPPs and the rest were seen by a combination of men's health APPS and urology attendings for second line treatments and penile doppler. Interestingly, 66% of men were interested in undergoing penile doppler to better understand the etiology of their ED. Hypertension (40%) and diabetes (22%) were the most common medical comorbidities. 36% of the cohort had a strong family history of cardiac disease. Conclusions Men with ED can be effectively triaged through a website application. Most men with pde5 refractory ED wish to pursue penile doppler. The majority of patients seen had watched educational video material ahead of time, facilitating a more sophisticated and streamlined patient interaction. Disclosure No

ABSTRACT Introduction Penile length loss and erectile dysfunction (ED) are common post-prostatectomy. Recent results from a randomized, controlled study (RCT) of RestoreX penile traction therapy (RxPTT) demonstrated preserved erectile function and penile length improvements in men post-prostatectomy. Objective To report outcomes of the open label phase (6-9 month time point) of the previously noted RCT comparing efficacy of RxPTT to control in men post-prostatectomy. Methods A randomized, controlled trial (NCT03500419) has been completed of 82 men post-prostatectomy. Men were randomized 1-month post-prostatectomy to no therapy (control, n=27) or RxPTT (n=55) for 5 months. Participants then entered an open label phase for 3 months. Assessments included stretched penile length (corona), standardized (International Index of Erectile Function [IIEF]), and non-standardized questionnaires. Comparisons were performed of men who utilized traction at least 15 minutes daily for both phases to men who were originally control and continued with no treatment (as-treated analysis). Analyses were also performed of men who crossed over from control to >15 min daily (crossover to treatment) and those who were originally in the treatment group and continued with >15 min daily use during the open label phase (ongoing treatment). Results Of the 82 men enrolled (mean age 58.6), 55 had 6-month, and 42 had 9-month data available to review. Baseline characteristics (IIEF scores, penile length) were similar between cohorts. In the as-treated analysis (no treatment n=7, RxPTT x 8 months n=12, respectively), differences were as noted: IIEF-EFD (-8 vs -0.5, p=0.19), IIEF-OFD (-3 vs -2, p=0.86), IIEF-SD (-1 vs 0.5, p=0.09), IIEF-ISD (-3 vs -0.5, p=0.31), IIEF-OSD (-2 vs 0, p=0.29), penile length (-0.1 vs +1.8 cm, p<0.01), PDE5 use (86% vs 75%, p=0.57), intracavernosal injection use (86% vs 17%, p<0.01). Comparing men who did not use therapy at any time (n=7) to those who crossed over to RxPTT during the open label phase (n=8) demonstrated the following results: IIEF-EFD (-8 vs -6, p=0.49), IIEF-OFD (-3 vs -1, p=0.90), IIEF-SD (-1 vs 0, p=0.55), IIEF-ISD (-3 vs -1, p=0.45), IIEF-OSD (-2 vs -1, p=0.51), penile length (-0.1 vs +0.69 cm, p=0.39). Men who crossed over from RxPTT to no treatment (n=10) had relatively preserved improvements compared to those who continued with RxPTT during the open label phase (n=12) compared to baseline, respectively: IIEF-EFD (0 vs -0.5, p=0.95), IIEF-OFD (-3.5 vs -2, p=0.97), IIEF-SD (0 vs 0.5, p=0.18), IIEF-ISD (0 vs -0.5, p=0.87), IIEF-OSD (0 vs 0, p=0.66), penile length (+1.8 vs +1.8, p=0.99). Conclusions Although sample size and statistical power are limited, results from the open label phase confirm earlier findings of preserved sexual function and penile length in men treated with RxPTT compared to controls. Men who crossed over from controls to treatment experience benefits, although not as significant as those who were treated beginning at 1 month post-prostatectomy. Men who stopped therapy after 6 months demonstrated stable improvements from baseline, suggesting a preserved effect of RxPTT even after discontinuing use. If validated with external series, these findings would represent a significant advancement in the prevention of sexual dysfunction post-prostatectomy. Disclosure No

ABSTRACT Introduction Congenital penile curvature is a relatively uncommon condition characterized by penile angulation. Similar to Peyronie's Disease (PD), this condition has historically been managed with various surgical techniques. Given the efficacy of Collagenase Clostridium Histolyticum (CCH) in men with PD, our team has elected to treat men with CPD with CCH injections. Objective To describe outcomes of CPD men treated with CCH injections and to compare against a traditional PD cohort. Methods A prospective database has been maintained of all men undergoing CCH injections by our team since Jan 2014. The specific CCH administration protocol has been modified over time and currently includes combined use of RestoreX traction therapy, sildenafil, 0.9 mg of CCH diluted into 0.7 ml, injections performed at the point of maximal curvature, and aggressive manual modeling. Curvatures were measured in two planes (dorsal and lateral), with the combined measure reported as a composite. Outcomes were reported based on the most recent curvature assessment obtained minus baseline. Men were included if they received at least one series of CCH injections and had at least one baseline and follow-up curvature assessment available. Results A total of 272 men comprised the current cohort, with 23 exhibiting CPD and 249 PD. Mean age was higher in PD men (57.4 vs 38.4, p<0.0001), and mean PD duration was 18 months in PD men. Median baseline curvature was non-statistically higher in PD (65 vs 55 degrees, p=0.06). Baseline curvature directions for PD and CPD, respectively were: dorsal (82% vs 35%, p<0.0001), lateral (58% vs 78%, p<0.05), ventral (11% vs 35%, p<0.01). Following treatment with CCH, median curvature improvement was similar between cohorts, with 20 degrees (IQR 5, 35) for PD and 20 degrees (IQR 5, 30) for CPD, p=0.62. Percentage improvement from baseline was non-statistically higher in PD men (33% vs 29%, p=0.99). Conclusions Treatment of CPD men with CCH is a viable therapeutic option and provides similar benefits to those observed in men with PD. Disclosure No

ABSTRACT Introduction Collagenase Clostridium Histolyticum (CCH) is commonly injected at the point of maximal curvature (POMC) for Peyronie's Disease (PD). However, many providers only evaluate the POMC at baseline and do not reassess during CCH injections. As PD plaques often extend over an extended region, it is currently unknown how much the POMC may change throughout a course of CCH treatment. Objective We sought to evaluate for changes in POMC between series among men undergoing CCH injections. Methods A prospective database has been maintained of PD men undergoing CCH injections at two institutions. POMC assessments were obtained prior to each series of injections after pharmacologic erection and were measured from the coronal margin to POMC. An analysis was performed comparing changes in POMC throughout the CCH course, including associated baseline demographic and disease characteristics. Results A total of 445 men (mean age 55.9, mean PD duration 30.6 months) underwent CCH injections from Jan 2014 through Feb 2021. The mean baseline composite curvature was 63.7° (SD 23.7), and the mean distance to curvature was 3.1 cm. Among men who completed 4 series of CCH injections, the mean improvement was 21° (SD 20.6) or 31.7% (SD 33%). In reviewing changes in POMC, the largest change observed at any point within the CCH series was a median 1 cm (IQR 0.5, 2 cm; range 0, 9.5 cm). Compared to baseline, 58% of men experienced a POMC change of 1 cm or greater, 25% 2 cm or greater, and 12% 3 cm or greater during the course of CCH treatment. Age, duration of PD, and baseline curvature were not associated with changes in POMC, although the POMC itself was associated with extent of changes, with proximal curves more likely to experience more notable changes compared to distal ones (p<0.0001). The total improvement in curve was also variably associated with change in POMC, with those experiencing greater improvements noted to have larger change in POMC (p<0.05 for changes in composite curvature and p=0.07 for percent change from baseline). These findings would suggest significant evolution of the POMC during a course of CCH, particularly among men with mid shaft or proximal curves and among those with greater curve improvements. Findings would support a role for repeat curvature assessments prior to each series of CCH injections. Conclusions Based on data from a prospective, two-institution series of PD men undergoing CCH injections, the POMC changes by ≥1 cm in the majority of men. Given the small volume injected with each CCH series, the clinical relevance of these findings and their impact on injector protocols merit further investigation. Disclosure No

ABSTRACT Introduction The efficacy and safety of collagenase clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD) were demonstrated in two phase 3, randomized, double-blind, placebo-controlled studies. CCH injections were administered in up to 4 treatment cycles at 6-week intervals; each cycle included two injections 1-3 days apart. Objective To evaluate incremental changes in penile curvature over the course of CCH treatment in men with PD. Methods A post hoc analysis was conducted using pooled data from the 2 placebo-controlled trials. Change from baseline and from the previous penile curvature measurement were calculated after each of the 4 treatment cycles (Weeks 6, 12, 18, and 24). For all patients, treatment included penile plaque modeling. For CCH vs placebo, mean percentage change in penile curvature was compared using a two-sample t-test; percentage of patients classified as treatment responders (defined as curvature reduction ≥20%) was compared using Fisher's exact test. Results The population included 832 adult men (CCH [n=551]; placebo [n=281]) who received ≥1 injection of study medication. At baseline, mean ± standard deviation (SD) penile curvature was 50.6±14.7 degrees in the CCH group and 50.4±14.1 degrees in the placebo group. Compared with baseline, the mean ± SD percentage change in penile curvature was -12.8±20.3% for CCH vs -6.2±18.8% for placebo after the first treatment cycle, -22.6±23.5% vs -10.6±23.1% after the second, -29.9±25.0% vs -14.6±24.0% after the third, and -33.1±28.0% vs -16.6±25.5% after the fourth (all P<0.001 vs placebo; Figure 1A). Comparing change from the previous measurement (ie, incremental change from previous treatment cycle [eg, between first and second; second and third, etc]), mean ± SD percentage reduction in penile curvature was 11.1±21.8% vs 5.0±16.4% after the second treatment cycle (P<0.001 vs placebo), 9.6±21.8% vs 3.9±17.0% after the third (P<0.001) and 6.3±23.0% vs 2.0±17.2% after the fourth (P=0.009; Figure 1B). The percentage of patients with ≥20% reduction in penile curvature since the previous measurement (cycle) was 29.9% for CCH group vs 18.3% for the placebo group after the first treatment cycle (P=0.0003), 29.1% vs 16.9% after the second (P=0.0002), 25.2% vs 12.8% after the third (P<0.0001), and 20.2% vs 10.9% after the fourth (P=0.001). For patients with a response after 2 treatment cycles (CCH [n=219]; placebo [n=77]), 40.2% of the CCH-treated patients vs 19.5% of the placebo-treated patients had an additional reduction of ≥20% after completing 4 treatment cycles (P=0.001). In patients with <20% reduction after the initial 2 treatment cycles (CCH [n=205]; placebo [n=168]), 29.8% of patients in the CCH group were classified as treatment responders after completing the fourth injection cycle (versus 20.8% of placebo-treated patients; P=0.057). Conclusions Data support that incremental benefits were obtained from each of the 4 CCH treatment cycles administered to men with Peyronie's disease. Results would suggest benefits with performing a full series of 4 CCH injections, even among men who are initial non-responders. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Inc. Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals Inc.