Ziegelmann, M.

Abstract Introduction Age is often correlated with various medical conditions, including bother with the condition itself. Peyronie’s disease (PD) is a condition which is most often associated with men in their 50-60’s, however, it does affect younger men as well. Anecdotally, younger men with PD appear to be more bothered by their condition compared to older men. We therefore sought to evaluate whether there is a difference among older vs younger men as to the degree of bother linked to PD. Objective To evaluate age as a potential predictor of bother associated with PD. Methods A prospective database has been maintained of men seeking treatment for PD. Beginning in Feb 2020, we began implementing men routinely completed standardized intake questionnaires relating to PD, including the Peyronie’s Disease Questionnaire (PDQ). The PDQ consists of 15 questions broken down into three key subdomains: psychological and physical, penile pain, and symptom bother. Men who had completed the PDQ questionnaire were evaluated to determine the correlation between various clinicopathologic variables and the PDQ-bother domain. Results A total of 645 men were seen for symptoms of PD and had PDQ questionnaire data available for review. Baseline demographics included a mean age was 51.8 years (SD 17.6), mean PD symptom duration 31.3 months (SD 65.3), estimated curve of 40.9 degrees (SD 26.8), and mean PDQ-Bother score 8.9 (SD 3.1 – Note: lower is better). Several clinicopathology variables were found to be associated with increased PDQ-bother scores, including age (younger = less bothered, parameter estimate -.0.03, p=0.03), the presence of indentation or hourglass (yes 9.4, no 8.4, p<0.05), pain (yes 9.3, no 8.5, p=0.16), PD preventing penetrative intercourse (yes 9.5, no 8.7, p=0.07), penile shortening (yes 9.3, no 8.7, p=0.10), subjective erectile dysfunction (yes 9.6, no 8.5, p<0.01), and subjective premature ejaculation (yes 9.8, no 8.4, p<0.01). Interestingly, several variables did not correlate, including the duration of relationship, frequency of intercourse, duration of symptoms, direction of curve, degree of curvature, partner pain with intercourse, or libido. Conclusions Several notable factors are associated with PD bother (as assessed by the PDQ-bother domain), and equally importantly, several factors are surprisingly not associated (e.g. curvature degree and direction). These factors provide useful information to the practicing clinician to help better identify men who may be at greater risk for bother associated with the condition. Disclosure No

Abstract Introduction Peyronie’s disease (PD), estimated to affect around 10% of the male population, is an acquired disorder of penile fibrotic tissue. The only FDA approved medical treatment for PD is Intralesional Collagenase Clostridium Histolyticum (CCh). CCh is a mixture of AUX1 and AUXII, two different forms of collagenase that cleave collage type I and type III, leading to plaque degradation. PD plaques, however, also contain fibrin and calcium which CCh is unable to digest. It is unknown if plaque calcification prevents collagenolysis with CCh. Objective To determine if calcification prevents collageolysis of PD plaques with CCh. Methods Calcified PD plaques were collected from five males undergoing excision and grafting for PD. Control tissue was collected from five males undergoing penile implant surgery for erectile dysfunction, with no known history of PD. Tissue samples were then divided into equal weights and incubated with CCh or PBS for 24 hours. The CCh or PBS was injected into the tissue (control or plaque) to mimic administration of CCH for treatment of PD. Following incubation, the fluid (CCh or PBS) was measured for soluble collagen amount and tissue was subjected to Picrosirius Red and H&E staining. Results There was a higher concentration of soluble collagen in the tissue (control and plaque) incubated in CCh (301ug, SD 21.1) compared to the issue incubated in PBS (32.5ug, SD 3.7) (p=0.02). Additionally, there was less type 1 and 3 collagen present in the CCh condition (mean 0.12, SD=0.08), when compared to the PBS condition (0.44, SD=0.17) (p=0.002). However, when comparing within the CCh condition to look at differences between tissue types (calcified vs. control) no differences were found. There was a similar amount of soluble collagen in the CCh control condition (316ug, SD 35) and the CCh calcified condition (286ug, SD 11) (p=0.06). Similarly, the PBS control condition (30ug, SD17) and the PBS calcified condition (35ug, SD 48) were found to have no significant differences in collagen concentration (p=0.4). Finally, there were no significant differences found in type I/III collagen staining between tissues in the CCh condition, with control (0.08, SD=0.02) and calcified (0.17, SD=0.09) demonstrating no significant difference (p=0.08). Tissues in the PBS condition, control (0.5, SD=0.23) and calcified (0.39, SD=0.39), similarly were not significant (p=0.2) (table 1). Conclusions CCh is capable of breaking down collagen in calcified plaques. Further research into CCh as a treatment option for PD calcified plaques is necessary. 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: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc.

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH), few studies have been able to identify variables which predict curve improvements, with baseline extent of curvature most highly correlated. In addition to extent of baseline curvature, our team has previously identified curve direction and plaque calcification as additional predictive variables. We therefore sought to create an integrated predictive model which incorporated several factors to better estimate anticipated outcomes. Objective To report outcomes of a novel scoring system designed to better predict outcomes of men undergoing CCH injections for Peyronie’s disease (PD). Methods A prospective database has been maintained of men undergoing CCH injections for PD. Data were reviewed to identify variables predictive of curve improvements in men with isolated curvature as well as among those with key characteristics, including indentations, hourglass deformities, penile tapering, and calcification. A predictive model was subsequently developed to improve correlations between disease factors and subsequent CCH outcomes. The final model (CLINiC Score) assigned points as follows: +1 point for every 10 degrees of curvature (C for Curvature), +5 points for penile narrowing >25% (IN for INdent), +3 points for narrowing 0-25%, -4 points for pure lateral curvatures (L for Lateral), and -2 points for plaque calcification (C for Calcification). Patients were assigned scores based on the CLINiC model, and results were correlated with final curve outcomes. Results A total of 476 PD men were included in the current analysis. Baseline variables for the cohort included a mean age of 55.6 yrs (SD 10.9), PD duration 31.9 months (SD 61.4), composite curvature 64.6 degrees (SD 23.9), 47% with indentations, 42% with hourglass deformity, and 17% with calcification. The mean CLINiC score for the cohort was 6.9 (SD 3.4). For the overall cohort, the use of the CLINiC score increased the correlation coefficient from 0.35 to 0.46 (r-squared 0.13 vs 0.21), with a predictive linear formula of 2.1 - 3.2 * CLINiC score. The difference was more pronounced among a subset cohort of men who had pure lateral curvatures, plaque calcification, or narrowing deformity. In comparing the CLINiC predictive model to baseline curve alone, the correlation coefficient increased to 0.54 (r-squared 0.29, p<0.0001) compared to 0.38 (r-squared 0.15, p<0.001). The linear equation to predict curve improvement outcomes using the CLINiC score was 2.2 - 3.5 * total CLINiC score. Conclusions Use of a novel scoring system (CLINiC) improves upon baseline curvature alone to predict post-CCH curve improvements, with the difference more pronounced among men with pure lateral curvatures, plaque calcification, and/or narrowing deformities. External validation is warranted. Disclosure No

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 have previously reported outcomes of men undergoing a more aggressive protocol for CCH injections. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel, aggressive protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men are randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes are subsequently compared between treatment and control groups. Key measures include 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 11/40 men have been randomized to date, with one having completed four series of CCH injections, three completing one series, and three completing two series. The average age of the cohort is 64.4 years, with a mean PD duration of 28.1 months. Mean baseline curvature was 82.9 degrees (composite curve). The average estimated improvement with prior CCH injections (before enrollment in the current study) was 10%. Preliminary outcomes of men who had completed one series and had a follow-up curve assessment available (n=3) demonstrated an absolute improvement of 28.3 degrees (42%). Of the one patient who completed four full series, the absolute curve improvement was 55 degrees (65%). The overall range of improvement among the four men was 20 to 55 degrees or 31 to 65%, with no patients failing to experience improvements thus far. Conclusions Preliminary data suggests that a repeat course of CCH using a previously described more aggressive administration protocol is effective at improving penile curvature in the majority of men. It is unclear if the improvements are due to the difference in administration protocol, or due to the repeat course of CCH alone. Given the very preliminary nature of the current results, additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. Specifically, investigators have compared relative utilization, costs, and outcomes with varying conclusions. Objective To compare various objective and subjective outcome measures between men undergoing CCH or surgery for PD. Methods A randomized, controlled trial (NCT04786106) is ongoing. Participants are randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD. Objective, standardized (International Index of Erectile Function [IIEF] and Peyronie’s Disease Questionnaire [PDQ]), and non-standardized assessments are obtained at baseline, and post-treatment at 3, 6, 12, 24, 36, 48, and 60 months. Key outcomes include differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Curvature is measured in two planes and summed to provide a composite curvature. Penile length is measured from pubic symphysis to corona. All therapies were stopped prior to the 3-month time point (i.e. traction and sildenafil). Results A total of 40 men have been randomized, with 3-month data available on 27 men (CCH=14, surgery=13) and 12-month data on 15 men (CCH=5, surgery=10). Mean age at enrollment was 54.9 years, PD duration 36.6 months (mo), composite curvature 72.3 degrees (deg), and penile length 12.7 cm. All baseline variables were statistically similar between cohorts. Regarding the primary outcome, post-treatment, CCH men reported higher overall satisfaction (3-months: 100% vs 88% surgery, p=0.16; 12-months 80% vs 70%, p=0.52). For secondary outcomes at 3 months, the median differences between CCH and surgery respectively were: IIEF-EFD (+3.5 vs +7, p=0.64), PDQ-physical (-10 vs -7, p=0.47, note: lower is better for PDQ scales), PDQ-pain (-2 vs -0.5, p=0.21), PDQ-bother (-4.5 vs -8.5, p=0.60), length change (+1.0 vs -0.5 cm, p<0.01), curvature absolute change (-26 vs -65 degrees, p=0.01), and curvature percentage improvement (46% vs 84%, p<0.01). More CCH men felt that treatment improved sexual function (86% vs 79%, p=0.45), erectile function (64% vs 56%, p=0.04), penile length (36% vs 6%, p<0.0001), and had less impact on sensation (14% less sensation vs 56%, p<0.01), while surgery men were more likely to report satisfaction with curvature (75% vs 64%, p=0.52). 100% of men in both groups would recommend treatment to a friend at 3 months, whereas 100% of CCH vs 70% of surgery men would recommend their therapy at 12 months. When asked which treatment they would pick if they could start again, at 3 months 100% of CCH men reported CCH and/or traction, while 79% of surgery men indicated surgery. Conclusions Preliminary data suggests that, when compared to surgery, CCH results in higher overall satisfaction (not statistically significant), decreased curve improvement, improved penile length, and fewer impacts on erectile function and sensation. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study

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 The COVID-19 pandemic has had a significant impact on global health. During uncertain times, priorities amongst patients shifted as many faced health concerns, economic uncertainty, and isolation. Access to general medical care during 2020 was challenging for many Americans who spent the year in quarantine. Without access to care, we hypothesize that patients were less likely to search for treatment options for a non-emergent condition like erectile dysfunction. Objective Herein, we aim to report on Google search trends observed in the pre COVID and post COVID era. Methods Google Trends was analyzed using search terms related to erectile dysfunction between June 2018 and June 2021. The search volume index (SVI), a relative measure of search volume on Google, was obtained for the following terms: erectile dysfunction, viagra, trimix, penile pump, and penile implant. Student t test was used to compare changes in mean SVI for each month compared to the same month one year prior. Results Compared to one year prior, the search for erectile dysfunction remained relatively stable over time with the exception of three months (9% decline Mar 2020, 38% increase Jan 2021, 8% increase Jun 2021). When compared to the preceding year, searches for Viagra declined during 9/37 (24%) months analyzed including Mar-Jun 2020, which coincided with the early part of the COVID-19 pandemic (p<0.05 for all). The only statistically significant increase occurred Oct 2020, a 16% change compared to Oct 2019 (p<0.05). In contrast, search for trimix did not change significantly over time except for an increase of 62% Mar 2021 and 60% Apr 2021 (p<0.05 for all). Search for the term penile pump did not change over time except for a 16 and 10% decline early during the pandemic, Feb and Mar 2020, respectively (p<0.05 for all). Lastly, search for penile implant declined 37% Mar 2020 and 32% Apr 2020 compared to 2019, and increased by 67% May 2021 compared to May 2020 (p<0.05 for all). Conclusions COVID-19 represented a major global health crisis, raising concerns and uncertainties for many. Erectile dysfunction remained a constant source of online interest. Despite limited access to medical care for elective conditions, only a few isolated increases in Google SVI were noted, most of which occurred during 2021 compared to 2020. This may be a reflection of the general public's lack of familiarity with treatments other than phosphodiesterase-5 inhibitors. Disclosure No

ABSTRACT Introduction Introduction:: Chronic scrotal content pain (CSCP) is generally defined by persistent and bothersome pain present for > 3-months. This symptom complex leads to frustration for patients and providers alike, as the underlying etiology varies and in many instances is unknown. Scrotal pain may arise from outside the scrotal contents, as is seen with musculoskeletal conditions involving the hips, lower back, and pelvic musculature. Identifying those patients who have signs or symptoms of a musculoskeletal etiology earlier in their clinical course will allow for a more streamlined treatment pathway and minimize the need for unnecessary referrals. Objective To review historical and examination findings in patients presenting to a tertiary care center for evaluation of chronic testicular pain. Methods We reviewed our clinical experience with referrals for surgical intervention for “chronic testicular pain” at a tertiary care medical center between July 2019 and October 2020. Prior to scheduling an appointment, patients are queried via a list of questions to gather additional information in order to determine whether specialist consultation is indicated. Pertinent information was collected including historical patient data, physical examination findings, laboratory and imaging results, and treatment as recommended by the assessing physician. In addition, we gathered data on the number of prior consults and interventions performed by outside clinicians. The data was summarized to present a cross-sectional representation of patients presenting for CSCP. Results In total, 126 patients were seen for a primary chief complaint of CSCP. Mean patient age was 45 years [standard deviation (SD) 15]. 31 (24%), 55 (44%), and 40 (32%) were self-referred or referred by their primary care provider or a urologist, respectively. 88 patients (70%) had seen at least one prior urologist. 22/126 (17%) reported bilateral testicular pain. 29 patients (24%) had undergone a prior unsuccessful surgical intervention for their pain. On examination, reproducible testicular tenderness was present in only 57 patients (45%), despite 109 patients (87%) stating testicular pain as their primary chief complaint. Digital rectal examination of the pelvic floor musculature was positive for tenderness in 31/126 patients (25%), suggesting a possible pelvic floor contribution. After thorough assessment, musculoskeletal etiologies were suspected to underlie CSCP in 49 patients (39%), prompting additional evaluation and/or referrals. This included 35 patients (28%) who were specifically referred to a pelvic floor physical therapy specialist. Surgery was recommended in 68/126 patients (54%), including microdenervation of the spermatic cord in 22% (after successful diagnostic spermatic cord block), and epididymectomy in 13%. Conclusions CSCP presents with a wide array of concurrent symptoms. The history and physical examination must include assessments for concurrent abdominal, back, hip, and other genital/pelvic pain that may lend towards an alternative non-urologic treatment pathway. Disclosure No

ABSTRACT Introduction Penile prosthesis (PP) implantation with concurrent straightening maneuvers is the gold standard surgical therapy for men with Peyronie's Disease (PD) and concurrent medication-refractory ED. Satisfaction rates exceed 80-90% in modern series. PD is characterized by other bothersome effects on penile morphology (i.e. penile shortening) that also negatively impact patient satisfaction with PP. We hypothesized that men with both PD+ED would report lower overall satisfaction with PP implantation compared to those with ED alone. Objective To compare patient outcomes in a cohort of patients undergoing PP implantation for ED with and without concurrent PD. Methods We identified all patients who underwent PP implantation by a single surgeon between May 2012 and August 2019 (n=354). A retrospective chart review was performed to evaluate pertinent clinical demographics and surgical outcomes. A survey was mailed to all patients in July 2019. This included validated ED questionnaires (IIEF, EDITS, and QOLSP) and clinician-derived questions to evaluate subjective outcomes. Survey results were compared between those patients with and without a history of PD, using two-sample student t- and chi-squared tests (p-value < 0.05 considered significant). Results 79 patients completed the survey (response rate 22%), including 38 (48%) with PD+ED. Mean survey follow-up duration was 45.5 (SD 19.5) months. There was no significant difference in patient demographics amongst those patients who did and did not respond to the survey. Amongst survey respondents, the mean preoperative IIEF-EF score was significantly higher for patients with PD+ED (10.2; SD 9.1) compared to those with ED alone (3.9; SD 5.0, p=0.003). Respondents with a history of both PD+ED were also less likely to have previously used oral therapy and intracavernosal injection to treat ED prior to PP implantation (p<0.009). For those respondents with PD+ED, mean preoperative curvature was 59O (SD 43). Adjunctive straightening maneuvers at the time of PP implantation included manual modeling (87%), plication (5%), and incision/grafting (50%). Overall, device infection occurred in 4/79 patients (5%), and mechanical malfunction occurred in 3/79 (4%). 87% of all survey respondents felt their ED was “very much” or “much” improved. 80% stated they would recommend PP to a friend. 60% reported postoperative penile length loss, but only 35% were “dissatisfied” with current length and only 20% were dissatisfied with penile girth. In those with PD+ED, 91% were satisfied with the degree of penile straightening. There was no significant difference in patient-reported outcomes pertaining to length, girth, and overall satisfaction between those with and without PD. The mean follow-up IIEF-EF was 27.4 (SD 5.7), mean EDITS was 18 (SD 8), and mean QOLSP was 55 (SD 15). Once again, there was no significant difference in these outcomes based on the presence of PD. Conclusions PP results in high rates of patient satisfaction. The presence of concurrent PD, even amongst those requiring adjunctive maneuvers, does not appear to significantly impact patient outcomes. While there are inherent limitations to a survey-based study including reporter bias, these results support the use of PP and concurrent straightening as an excellent treatment option for men with PD and ED. Disclosure Yes, this is sponsored by industry/sponsor: This project was funded by an investigator-initiated grant from Coloplast Corporation. Clarification: Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Corporation (Dr. Laurence Levine - consultant); Boston Scientific (Dr. Laurence Levine - Consultant)

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