Green, B

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 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 Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. Objective To report outcomes of a more aggressive CCH injection / traction protocol in men with PD. Methods A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. Results A total of 320 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8 (SD 10.4), with a mean PD duration of 27.8 months (SD 53) and a median baseline composite curvature of 64 degrees (IQR 45-80). Curvature improvements (most recent minus baseline) improved over time, correlating with increased injection experience and implementation of more aggressive traction protocols: 2014-2020 (20 degrees, 29% improvement) vs 2020-mid 2021 (27.8 degrees, 50%, p<0.001). When men were stratified by those who either completed 8 injections or indicated that they were satisfied with outcomes (n=147), median results were more pronounced: 2014-2017 (29% improvement), 2018 (38%), 2019 (47%), 2020-mid 2021 (59%), p<0.01. Conclusions Progressive implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Disclosure Work supported by industry: no.

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 at ***. 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 32 men have been randomized to date (CCH=17, surgery=15), with 3-month data available on 8 men (CCH=4, surgery=4). Mean age at enrollment was 55.8 years (SD 14.4), PD duration 38 months (SD 49.5), curvature 74.1 degrees (SD 20.9), and penile length 12.5 cm (SD 1.5). All baseline variables were statistically similar between cohorts. Regarding the primary outcome, at 3 months post-treatment, CCH men reported higher overall satisfaction (not statistically significant; 50% very satisfied, 50% somewhat satisfied; surgery 100% somewhat satisfied, p=0.06). For secondary outcomes at 3 months, the median differences between CCH and surgery respectively were: IIEF-EFD (+4 vs +4, p=1.0), PDQ-physical (-10 vs -6.5, p=0.14, note: lower is better for PDQ scales), PDQ-pain (-12 vs 0.5, p=0.77), PDQ-bother (-9 vs -8, p=0.77), length change (+0.8 vs 0 cm, p=0.29), curvature absolute change (-22.5 vs -80 degrees, p=0.11), and curvature percentage improvement (41% vs 85%, p=0.11). An equal number of CCH and surgery men felt that treatment improved sexual function (75%) and their ability to have sex (100%) and were subjectively happy with their curvature (50%). Men in the surgery arm were more likely to report (note that some are not statistically significant) subjectively worsened erectile function (50% vs 0%, p=0.15), shorter penile length (75% vs 0%, p=0.02), lower satisfaction with penile length (50% satisfied vs 75%, p=0.46), improved hourglass (33% vs 0%, p=0.42), and were less likely to report that they would repeat treatment without reservation (50% vs 75%, p=0.11). When asked which treatment they would pick if they could start again, 100% of CCH men reported CCH and/or traction, while 50% of surgery men indicated surgery, 25% CCH, and 25% other (p<0.05). Conclusions The current data are too preliminary to draw any viable conclusions on differences between CCH and surgery for PD. Disclosure Work supported by industry: yes, by Endo Pharmaceutical.

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