A survey to assess practice patterns among clinicians administering collagenase Clostridium histolyticum for Peyronie's disease.

Peyronie's disease (PD) is a fibroproliferative disorder of the tunica albuginea characterized by localized plaque formation, penile curvature, and erectile dysfunction, most commonly affecting men between 40 and 70years of age. Although François Gigot de La Peyronie is credited with the first formal description of the disease in 1743, depictions of penile curvature predate his description by millennia. This review aims to provide a comprehensive understanding of the historical and contemporary evolution of therapeutic strategies for PD, highlighting the shift from anecdotal remedies to evidence-based approaches. PubMed, Cochrane, and Embase databases were searched without restrictions on publication date, using keywords related to PD and its therapies. Key interventions, including oral and topical agents, intralesional injections, penile traction therapy (PTT), and surgical techniques, were analyzed in the context of clinical trial data and guideline recommendations. Early therapeutic approaches focused on oral and topical agents, which failed to demonstrate consistent efficacy in randomized trials. Intralesional injection (ILI) therapy has emerged as a leading option for nonsurgical management, with collagenase Clostridium histolyticum (CCH) as the standard treatment supported by robust evidence of significant improvements in penile curvature. PTT has undergone considerable refinement, with second-generation devices yielding excellent outcomes, particularly when combined with CCH. Surgical intervention remains the gold standard for definitive treatment of severe or complex deformities. Technical modifications have developed, including the use of biologic grafts, inflatable prosthesis placement with manual modeling, and graftless techniques such as tunica expansion and auxetics. A review of the historical progression of PD management demonstrates the shift from anecdotal claims of treatment efficacy to evidence-based practice. Current guidelines recommend ILI and PTT as first-line nonsurgical management, with surgery providing exceptional outcomes. Future progress aims to gain a greater molecular understanding of fibrosis and tissue remodeling to foster targeted therapies.

Peyronie's disease (PD) continues to represent one of the most challenging conditions in sexual medicine, particularly in its acute phase, where pain, progressive curvature, and psychological distress converge to disrupt patients' lives. For decades, clinicians have been limited to watchful waiting or off-label therapies, with collagenase Clostridium histolyticum (CCH) emerging as the most rigorously studied intralesional option in the chronic phase. Yet, the acute phase has largely remained an uncharted therapeutic territory. In this perspective, we present our preliminary clinical experience with Perovial® (IBSA, Italy), a novel intraplaque therapy administered in 10 weekly sessions, combined with daily vacuum therapy and penile modeling. Among 16 acute-phase patients with a median baseline curvature of 43° (IQR 30-62), we observed a median curvature reduction of 15° (IQR 7.5-19), significant pain relief, and no complications. These results, although preliminary, raise provocative questions: could Perovial® not only mirror but even surpass the benefits of CCH in acute disease? And more importantly, should the field of sexual medicine embrace earlier, mechanism-driven interventions rather than waiting for the disease to stabilize? We propose a possible game changer for acute PD.

In 2020, collagenase clostridium histolyticum (CCH) was withdrawn from markets in Europe, Asia, and Australia for Dupuytren's contracture (DC). The impact of this withdrawal on US treatment patterns remains unclear. This study evaluates national trends in DC management across Medicare and Medicaid populations. Using data from the Centers for Medicare and Medicaid Services Physician/Supplier Procedure Summary, all DC-related procedure claims from 2012 to 2022 were identified using Current Procedural Terminology (CPT) codes for open partial palmar fasciotomy (26045), open fasciectomy (26121, 26123, 26125), percutaneous needle aponeurotomy (26040), and collagenase injection (20527). Claims were analyzed by year, provider type, and place of service, normalized per 100 000 total claims. Between 2012 and 2022, 189 142 procedures were recorded. Overall intervention rates increased by 36%, from 35.87 to 49.10 per 100 000 claims. Collagenase injections rose 269%, while open fasciotomy declined 26%. Open fasciectomy remained the dominant treatment, accounting for over 60% of procedures. Notably, fasciectomy with digital release (26123, 26125) increased, while isolated palmar fasciectomy (26121) decreased. Office-based procedures rose from 14% to 21%, while ambulatory surgical centers remained most common (46% in 2022). Orthopedic surgeons were the leading providers, though hand specialists saw the largest proportional increase. Unlike international trends, US collagenase use continued to rise through 2022. Open fasciectomy remained primary, with a shift toward minimally invasive treatments and outpatient settings. Hand specialists are increasingly involved, though orthopedic surgeons lead in volume. These findings reflect evolving care models and highlight the need for continued monitoring of provider patterns and access to DC treatment.

Abstract Introduction In 2010, the FDA approved collagenase clostridium histolyticum (CCH), marketed as Xiaflex, for treating Dupuytren’s contracture. In 2013, it was approved for use in Peyronie’s disease (PD). This historical review aimed to outline how the FDA's approval of CCH for Dupuytren’s directly led to its subsequent approval for use in PD, forever changing how PD is managed. Objective This study aims to evaluate how the FDA approval of collagenase clostridium histolyticum (CCH) for Dupuytren’s contracture influenced its subsequent adoption for Peyronie’s disease (PD). By reviewing publication trends, the study explores how CCH reshaped the landscape of nonsurgical PD management and replaced older therapies as the preferred first-line option. Methods A simple PubMed search was undertaken regarding all mentions of Dupytren’s contracture, CCH, and Peyronie’s disease from 1983 to 2024. Publications were analyzed and included if they mentioned CCH alongside Dupuytren’s and Peyronie’s. To explore public interest in the treatment approach to PD, publications mentioning Verapamil, Interferon, Pentoxifylline, and CCH in the context of treating PD were included. Results After the FDA approved CCH for Dupuytren’s contracture in February 2010, its safety and efficacy prompted exploration into other fibrotic disorders, notably PD. Before 2010, few publications suggested CCH as a possible treatment for PD, suggesting that its approval for use in Dupuytren’s influenced the exploration of it in PD (Figure 1). Later that year, in September 2010, the IMPRESS I and II trials began recruiting patients to look at CCH use in PD. IMPRESS III, the third trial, would eventually lead to FDA approval of CCH for PD in 2013. The IMPRESS I, II, and III trials demonstrated that CCH is an effective and well-tolerated injectable therapy for decreasing penile curvature and improving sexual function. Before CCH was approved for PD, the mainstay nonsurgical treatments for PD included oral therapy with Pentoxifylline and L-arginine and/or intralesional Verapamil or Interferon, all of which had mixed efficacy and a lack of large-scale trials. Since the 2013 FDA approval for CCH for PD, all of these other therapies have become less common in clinical practice, demonstrating a changed landscape in the treatment of PD (Figure 1). Conclusions Collagenase clostridium histolyticum (CCH) remains the only nonsurgical FDA-approved treatment for Dupuytren’s contracture and Peyrone’s Disease (PD) and has become the first-line treatment in men living with PD. The FDA approval of CCH for Dupuytren’s completely changed the treatment approach to PD and has led to significantly improved sexual and erectile function for many men living with this condition. 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 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 40 men have been randomized to date, with 31 having fully completed treatment. Mean age was 60 years, with a median PD duration of 26.5 months. Median composite baseline curvature was 65 degrees, with 43% having hourglass or indentation deformities, 8% calcification, median baseline IIEF-EFD 20, and 68% able to have penetrative intercourse. Median estimated improvement with the prior CCH series was 0% (IQR 0, 14), and the median number of prior injections was 8. The majority of men were dissatisfied with their prior series of CCH (68% vs 25% satisfied, 8% neutral). Of the 27 men who had completed the study protocol the median number of cycles administered was 2 (IQR 1, 4). Compared to the no treatment arm, treated men experienced significantly greater improvements (median 55 degrees vs 0, p<0.0001). Post-treatment IIEF-EFD was similar between groups (+1 vs -2.5, p=0.21). 89% of men reported a subjective major improvement in curvature, with the median subjectively estimated improvement 90% (IQR 75, 95). 29% reported improved sensitivity (59% no change), while 75% reported improved or no change in erectile function, with 6% unsure, and 19% worse. Post-treatment, 94% of men were satisfied with CCH as a treatment and 6% 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 Peyronie's disease (PD) causes penile deformity, pain, and erectile dysfunction, significantly impacting quality of life. Treatment options range from collagenase clostridium histolyticum (CCH) injections to surgical modalities. Objective This study aimed to evaluate and compare objective and patient-reported outcomes across contemporary PD treatments. Methods This retrospective analysis included patients undergoing treatment for PD at a single institution. Primary treatment groups were initially compared: CCH using traditional protocol, CCH with contemporary protocol including health care provider modeling using increased force, tunica albuginea plication (TAP) and partial plaque excision or incision and grafting (PEG). Outcomes assessed included changes in penile curvature (absolute and percentage) and PDQ (Peyronie's Disease Questionnaire) sub-scores for pain, psychological impact, and bother. Non-parametric statistical methods were employed. Overall group differences were assessed using the Kruskal-Wallis H test, followed by pairwise Wilcoxon rank-sum tests with Bonferroni correction for post-hoc comparisons. Results A total of 114 patients who received PD treatment between 2020-2025 were included. 54 received CCH injections, (29 received a contemporary CCH protocol and 28 a traditional CCH protocol), 87 underwent surgery (TAP and/or PEG). When comparing outcomes between the contemporary CCH protocol, traditional CCH protocol and Surgery, Kruskal-Wallis tests revealed statistically significant overall differences among treatment groups for all outcomes, except not for PDQ Pain Change (p = 0.395). Post -hoc pairwise comparisons consistently demonstrated that the Surgery group achieved significantly greater curvature correction compared to all groups. No significant curvature change differences were observed between CCH traditional and contemporary protocols (p=0.9393). When comparing traditional CCH protocol to surgery, Surgery resulted in greater curvature improvement, (p<0.001), better PDQ psychological and Physical Symptoms subscore (p<0.001) and PDQ bother subscore (p< 0.001) However, when comparing the contemporary CCH protocol to surgery, there was no significant difference between groups in PDQ psychological and Physical Symptoms (p=0.2471) and PDQ bother (p=0.785) subscores, despite greater improvement in curvature with surgery. Conclusions The present study demonstrates that patient reported outcomes following contemporary CCH protocol result in satisfaction that is not inferior to satisfaction following Peyronie’s surgery despite surgery resulting in superior curvature improvement. Increasing data demonstrates that patient perception of improvement and satisfaction is not directly proportional to degree of curvature improvement. These findings offer valuable insights for counseling patients and guiding treatment selection in Peyronie's disease. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast, Endo

Abstract Introduction Significant clinical variations exist in the definitions of acute/active vs chronic/stable Peyronie’s Disease (PD). While the American Urological Association’s 2015 guidelines define the acute phase as involving symptoms that change and the presence of pain, they do not specify a timeframe. Historically, acute-phase features include penile pain and worsening curvature, with symptom duration ranging from less than 3 to 18 months. Although temporally categorizing PD may have academic value, it may unnecessarily limit or delay treatment. In the United States, collagenase clostridium histolyticum (CCH) is the only FDA-approved treatment for adult men with PD who have a palpable plaque and a curvature deformity of at least 30 degrees. Several real-world studies suggest CCH is safe and effective during the acute phase. Objective To evaluate differences in outcomes by penile pain and symptom duration and to determine whether these factors should inform timing of CCH treatment in men with Peyronie’s disease. Methods A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623). Men treated with CCH were stratified by baseline penile pain (Any Pain vs No Pain), based on both investigator-assessed and patient-reported measures. A subgroup analysis further stratified men with Any Pain by disease duration. The primary efficacy endpoint in the phase 3 study was the percentage change in penile curvature from baseline to week 52. A 2-sample t test was used to compare group means for each pain-related measure. Results A total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0%-36.7% improvement for the No Pain group vs 32.2%-33.9% improvement for the Any Pain group, P=0.14-0.65). Among those experiencing Any Pain, no statistical differences were observed in men with disease durations that were shorter (12-18 months; 21.8%-34.8% improvement) vs longer (greater than 18 months; 31.4%-36.8% improvement, P=0.20-0.95). Conclusions This study found similar curvature improvements among men treated with CCH regardless of baseline pain or disease duration. Results align with prior studies showing no outcome differences by pain status or disease phase. These findings suggest that pain and disease duration should not be viewed as contraindications to CCH or used to guide clinical decision-making. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction Peyronie's disease (PD) significantly diminishes quality of life by causing penile deformity, pain, and erectile dysfunction. In recent years, procedural refinements have improved outcomes for patients treated with Collagenase Clostridium Histolyticum (CCH). Objective Peyronie's disease (PD) significantly diminishes quality of life by causing penile deformity, pain, and erectile dysfunction. In recent years, procedural refinements have improved outcomes for patients treated with Collagenase Clostridium Histolyticum (CCH). Therefore, this study aimed to compare objective and patient-reported outcomes at our institution, tracking the results as these modified techniques were adopted over time. Methods This retrospective analysis included patients undergoing CCH treatment for PD at our institution. Primary treatment groups were stratified by year of treatment. Outcomes assessed included changes in penile curvature (absolute and percentage). Data is presented in as medians with IQR and % where appropriate. Results This study analyzed outcomes and patient characteristics among individuals receiving CCH injections, stratified by the year of their first injection (2023, 2024, and 2025). A total of 57 patients who received PD treatment between 2022-2025 were included. Through the years there is a visible difference in curve change, curve change % and also trends of different adjuvant measures such as the use of traction device (66.67% in 2023, compared to 100% in 2025) and the use of concomitant Tadalafil (44.44% in 2023, compared to 100% in 2025). Data is summarized in table 1. A boxplot of % of curve change over time, comparing objective treatment outcomes through the years, is shown in figure 1. Conclusions As CCH protocols have continued to evolve, our center has seen improved outcomes with the adoption of techniques such as healthcare provider modeling with increased force, concurrent traction therapy and tadalafil use, injecting while erect and decreased time between injections. Although gradual evolution of the protocol makes comparisons of individual modifications challenging, the overall trend is towards improved efficacy. These modifications suggest that CCH may allow for greater improvement than described in the IMPRESS trials, although external multi-center validation is needed. This study indicates that CCH protocol modification offers increasing curvature improvement over time. These findings, offer valuable insights for counseling patients and guiding treatment selection in Peyronie's disease. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast, Endo

Abstract Introduction While most patients with Peyronie’s disease (PD) present with dorsal or lateral curvature, a significant number have ventral curvature (VC). These patients face limited treatment options, as they were excluded from initial clinical trials of collagenase clostridium histolyticum (CCH) due to safety concerns related to the proximity of the injection site to the urethra. However, urethral involvement is rare, as PD plaques develop in the tunica albuginea rather than the corpus spongiosum surrounding the urethra. Moreover, multiple prospective and retrospective studies have demonstrated favorable outcomes with CCH treatment in men with VC. Objective To evaluate the effectiveness and safety of CCH in men with PD and VC in a multicenter, real-world, retrospective study. Methods This is an ongoing phase 4, multicenter, retrospective review of medical records from 15 US physician sites. Eligible patients consisted of patients who are: age ≥18 years with a diagnosis of VC in PD with a palpable plaque that was treated with CCH from 2014 to the study start date at each site. Patients missing baseline (BL; pretreatment) or final (last measurement within 6 months of final CCH treatment) penile curvature measurements were excluded. Effectiveness endpoints included percentage change in VC from BL to last visit, mean change in VC (in degrees) from BL to last visit, and proportion of patients with ≥30% improvement in VC from BL to last visit. Safety was assessed as proportions of patients reporting treatment-related adverse events (TRAEs) throughout the study period. Results As of April 22, 2025, there were 116 patients with mean (SD) age of 58 (10.3) years who were eligible for analysis. Mean baseline VC decreased from 58 degrees to 37 degrees at last visit (37% improvement). An improvement in VC of ≥30% was seen in 73/116 (63%) of patients, with 81/116 (69.8%) experiencing ≥20% improvement. At least 1 TRAE was reported by 12 (10%) patients. TRAEs were mild-to-moderate in severity in 9 (75%) patients and unknown in 3 patients, with most events (14/17 [82%]) related to injection site reactions. As of the data cut, there were no treatment-related serious or treatment-related severe AEs, no reports of urethral involvement or injury, and no reports of corporal rupture. Conclusions Men with PD who present with ventral curvature represent an underserved patient population. Concerns about potential urethral injury pose a significant barrier to both minimally invasive and surgical treatments, thereby limiting available therapeutic options. These updated results from a multi-institutional real-world clinical cohort align with previous findings, and demonstrate that the clinical effectiveness and safety profile of CCH is consistent with the profile of CCH seen in other clinical presentations of PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction Peyronie’s disease (PD) is an acquired connective tissue disorder characterized by fibrous plaque formation within the penile tunica albuginea. Some studies suggest that testosterone (T) levels may influence both the degree of penile curvature and outcomes following collagenase clostridium histolyticum (CCH) therapy, due to testosterone's role in collagen metabolism, tissue healing, and angiogenesis. However, smaller studies have found no association between baseline testosterone and treatment outcomes. Objective This study aimed to assess whether baseline T levels and testosterone therapy (TTH) during CCH treatment affect initial curvature severity and treatment outcomes in PD patients. Methods This multi-center, retrospective study included PD patients who received CCH injections. Inclusion criteria were no worsening curvature in the preceding 3 months and recorded baseline testosterone. Data extracted included demographics, pre- and post-treatment curvature, surgical conversion, hypogonadal status, and TTH use. Hypogonadism was defined as testosterone <300 mg/dL. Results Mann-Whitney U tests compared outcomes based on hypogonadal status and TRT use. CCH cycle requirements did not differ significantly between hypogonadal and eugonadal men (median = 8 cycles, p = 0.733), nor did baseline curvature (p = 0.902) or curvature change after treatment (p = 0.128). Surgical conversion rates were comparable (6.5% non-hypogonadal, 7.8% hypogonadal). For TRT, the number of CCH cycles were similar between groups (median = 8, p = 0.977), though baseline curvature was significantly higher in the TRT group (p = 0.012). Most TRT users (89%) had started TRT prior to CCH. Post-treatment curvature change (p = 0.706) and surgical conversion rates (6.5% non-TRT, 8.6% TRT) did not differ significantly. Conclusions Hypogonadism and TRT use did not significantly impact CCH cycles, curvature improvement, or surgical conversion rates. Men on TRT had higher baseline curvature, suggesting a potential influence of exogenous TTH on initial curvature severity. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Marius, Besins

Abstract Introduction PD is characterized by progressive fibrosis of the tunica albuginea of the corpora cavernosa and can result in penile deformity, sexual disability, pain, and emotional distress. Surgical treatments for PD include placement of a penile prosthesis, penile plication, and plaque incision and grafting. Commonly used nonsurgical treatment options for PD include intralesional injection with collagenase clostridium histolyticum (CCH), verapamil, or interferon. We conducted a cross-sectional survey of HCPs who treat men with PD. Objective To describe HCP attitudes, behaviors, and preferences for treating patients with PD. Methods Urologists and advanced practice providers (APPs) were recruited in 2023. Eligible physicians were American Board of Urology certified or eligible, had ≥2 years of experience, had seen ≥10 unique patients for PD in the past year with active management ≥1 patient, and could recall ≥1 treatment option for PD. APPs were required to practice in an office specializing in urology. A sub-specialization in men’s sexual health conditions was not required. Results were analyzed using descriptive statistics. Results A total of 135 HCPs completed the cross-sectional survey, 31% of whom were associated with the Sexual Medicine Society. HCPs reported seeing an average of 61 patients with PD in the preceding year with active management of an average of 52 patients, and 40% indicated that they anticipated the number of their PD patients to increase in the following year. HCPs indicated that 27% of their patients were diagnosed with PD while being treated or tested for other conditions. Most HCPs (69%) reported not using an intake questionnaire for PD diagnosis, and 15% indicated they do not usually screen for PD. HCPs reported that after initial diagnosis, 14% of patients were referred out. Of those remaining in active management, PD phase was chronic in 64% and acute in 36%. The Figure shows the first-line therapies for treatment-naive patients with chronic PD that were most frequently recommended by HCPs. HCPs reported a “highly satisfied” treatment satisfaction score of 41% for CCH (n=121), 11% for verapamil (n=80), and 15% for interferon (n=34) compared with 61% (n=122) and 44% (n=109) for penile implant and other surgery, respectively. Concern about penile rupture with CCH was reported by 56% of HCPs who had not prescribed CCH for PD (n=18) compared with 8% of HCPs who had prescribed CCH to ≥25% of their PD patients (n=25). Conclusions These findings offer some insight into treatment practices for men with PD. Survey respondents included both general practice urologists and HCPs subspecializing in men’s sexual health, which may have influenced the results. Notably, HCPs with no CCH-treatment experience expressed a heightened concern about penile rupture. The low usage of intake questionnaires suggests an opportunity for development of a PD-specific screening tool that can be used efficiently in clinical practice. The anticipated increase in the number of PD patients reported by 40% of respondents may reflect increased awareness of and/or willingness to talk about PD among both patients and providers, illustrating the value of continued education regarding diagnosis and treatment options for men with PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction Intralesional injection of collagenase clostridium histolyticum (CCH) is the only Food and Drug Administration (FDA) approved therapy for the treatment of Peyronie’s disease (PD). Initial clinical trials included patients with a palpable plaque and curvature deformity of ≥30 degrees in the stable phase, excluding patients in the active phase from treatment. Only a few studies have evaluated its safety and efficacy during the active phase of PD. Objective We aim to assess the effectiveness of CCH treatment in patients in the active phase compared to those in the stable phase of PD. Methods This is a multi-center, retrospective study. Clinical and demographic data were obtained. Patients were categorized into two groups: stable phase (no change in curvature within 3 months) and active phase PD (a change in curvature within 3 months). The primary outcome was absolute degree change from pre- to post-CCH treatment curvature assessed by goniometer. We also compared the groups based on total number of injections received (fewer than eight or eight). Results 401 patients received CCH for PD, with a mean age of 56.27 years (SD 9.36). Among these, 373 (93.02%) were in the stable phase, while 28 (6.98%) were in the active phase. The mean penile curvature before treatment was 46.62 degrees (SD 16.24) in the stable phase and 47.14 degrees (SD 18.78) in patients in the active phase (p = 0.887). Overall, the post-treatment change in curvature was not statistically different between the two groups: 16.20 degrees (SD 17.08) for patients in the stable phase and 21.36 degrees (SD 20.70) for those in the active phase (p = 0.209). In a sub-analysis based on the number of injections, patients in the active phase who received eight injections showed a more significant absolute change in curvature than those in the stable phase (24.19 degrees vs. 15.69 degrees, p = 0.039). However, for patients who did not complete all eight injections, there was no statistically significant difference between the two groups (16.82 degrees in the stable phase vs. 12.5 degrees in the active phase, p = 0.756). (Table 1) The most common reason for not completing the entire series of injections was loss to follow-up (54%). Conclusions In this series, patients in the active phase of PD who completed all eight CCH injections showed greater improvement in post-treatment penile curvature compared to those in the stable phase, suggesting that CCH injections can be effective as a treatment in both phases of PD. Disclosure No

Abstract Introduction Peyronie’s disease is characterized by the formation of fibrous plaques in the tunica albuginea of the corpora cavernosa, leading to varying degrees of penile curvature during erection. Collagenase Clostridium histolyticum (CCH) is currently the only non-surgical option available for correcting this curvature; however, patients often express reluctance to undergo penile injections due to perceived invasiveness. Objective This study aimed to investigate the potential influence of concomitant urologic conditions on the decision to pursue intralesional injection therapy for Peyronie’s disease. Methods We conducted a single-center retrospective study from January 2009 to December 2024, focusing on patients diagnosed with Peyronie’s disease. We collected demographic, clinical, and laboratory data from 943 patients, examining their histories of erectile dysfunction (ED), hypogonadism, and the utilization of intralesional therapy with CCH as well as mental health status. Chi-square tests were performed for statistical analysis of the collected data. Results Our analysis included 943 patients, with a mean age of 57.1 years. Among these, 314 patients (33.3%) underwent intralesional CCH injections. Within this cohort, concomitant urologic conditions were prevalent: hypogonadism was present in 52%, ED in 77%, and both diagnoses in 44% of patients. The likelihood of receiving intralesional injections increased with the presence of two or more urologic diagnoses (p < 0.05). Interestingly, patients with a history of mental health conditions, such as anxiety and depression, did not demonstrate a correlation with increased CCH usage as a treatment modality. Moreover, patients with coexisting Peyronie’s disease, Hypogonadism, and ED exhibited a significantly higher prevalence of anxiety and depression (p < 0.05) compared to those diagnosed solely with Peyronie’s, emphasizing the considerable impact of comorbid urologic conditions on mental health. Conclusions In our cohort of 943 patients with Peyronie’s disease, the use of intralesional CCH for treatment was more pronounced in men with both ED and hypogonadism than in those without these conditions. However, this association was not observed in men with hypogonadism alone, nor was there a significant relationship with anxiety or depression. Notably, patients with concomitant hypogonadism and ED showed a higher frequency of anxiety and depression compared to those without multiple sexual dysfunctions, highlighting the need for comprehensive mental health assessments and support in this population. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Marius, Besins

Abstract Introduction Intralesional collagenase clostridium histolyticum (CCH) is a widely used non-surgical treatment for Peyronie’s disease (PD). Despite its broad application across men of various ethnic backgrounds, data on outcomes in non-Caucasian populations remains limited. Objective This study aims to evaluate the success rate of CCH across different ethnic groups. Methods This study, approved by our Institutional Review Board, is a multi-center, retrospective analysis of patients who received CCH injections to treat PD. Clinical and demographic data were obtained. Patients were categorized into three groups: White, Black, and Hispanic. The primary outcome was an absolute degree of change from pre- to post-CCH treatment curvature, as assessed by a goniometer. Results A total of 385 men were included in the study. Of these, 335 (87%) were white, 23 (5.9%) were Black, and 27 (7.1%) were Hispanic. The overall mean age was 56.27 years (SD 9.36). The mean penile curvature before treatment was 46.66 degrees (SD 16.41), decreasing to 30.09 degrees (SD 17.27) after treatment, with an absolute change of 16.56 degrees (SD 17.38). In a subgroup analysis, these values were further stratified by ethnicity (Table 1), revealing no statistically significant differences among the ethnic groups. Conclusions In this cohort, the degree of change following CCH treatment did not differ significantly among White, Black, and Hispanic populations. Our findings suggest that patients can expect similar treatment outcomes regardless of ethnicity. However, the sample size for non-Caucasian men is still small and requires more extensive studies for validation. Disclosure No

Abstract Introduction Introduction: Peyronie’s disease (PD) is a fibrosing condition of the tunica albuginea characterized by a palpable plaque with varying impacts on the patient’s erection: curvature, shortening, indentations, hinging, and narrowing. Stepwise intralesional injection of collagenase clostridium histolyticum (CCH) is the only FDA approved medical treatment for PD. We retrospectively reviewed Xiaflex® treated patients for satisfaction with therapy or pursuit of subsequent surgery. Objective Objective: To assess global satisfaction with intralesional Xiaflex based on whether patients subsequently elected surgery. Methods Methods: This is a retrospective review of patients presenting with PD to a single center and managed by a single provider from 2020-2024 with six-month follow-up post-treatment. Patient presentations were recorded in an Institutional Review Board approved database. Data storage and analytics were conducted using REDCap. Results Results: The cohort for this study was 159 men treated with intralesional Xiaflex. 18 of the 159 were excluded from analysis due to ongoing treatment. 48.9% of patients (69/141) were satisfied with CCH outcomes and sought no further therapy. 51.1% of patients (72/141) were not satisfied with their outcomes. Of the patients not satisfied with treatment, 48/72 (66.7%) elected subsequent surgical interventions: 18 penile plications, 8 incision and grafting and 22 inflatable penile prostheses. 51.7% (73/141) of patients completed (8) CCH treatments. Among the 73 men who had a complete set of CCH injections, 24.6% (18/73) elected subsequent surgery. Among the patients who had fewer than 8 treatments 46.9% (30/64) elected surgery following Xiaflex. Conclusions Conclusion: If successful medical management of Peyronie’s disease is defined by men who decline subsequent surgical interventions, Xiaflex® was highly successful 75% (55/73). Patients who have Peyronie’s disease are highly motivated and will pursue surgical interventions following a trial of CCH. Disclosure No

Abstract Introduction The underlying etiology for Peyronie’s disease (PD) has historically been attributed to a combination of environmental and genetic factors. Recently, a novel genetic test (PeyroniesGene) was developed to identify genetic factors associated with PD. The current study was designed to evaluate the efficacy of PeyroniesGene in correctly identifying men with PD as well as correlating findings with disease severity. Objective To evaluate the predictive ability of a novel genetic test (PeyroniesGene) to detect factors associated with PD and other sexual dysfunctions. Methods A prospective cohort study is ongoing to compare genetic profiles of men with or without clinically diagnosed PD. All men underwent testing by the PeyroniesGene test, which evaluates three proprietary single nucleotide polymorphisms (SNP1-3). For each test, men were classified as being homozygous for one of the two alleles or heterozygous. The two cohorts were then compared to determine correlations with various sexual function factors. Two distinct scoring systems were created, with one used to predict PD and the second to predict response to Collagenase Clostridium histolyticum (CCH). Results A total of 311 men (PD = 155, non-PD = 156) have been enrolled to date, with genetic samples obtained and tested. Median age was 52, and median duration of PD was 15 months. Results of the PD scoring system demonstrated strong reliability in identifying men and higher or lower risk of having PD as well as those reporting trauma as a suspected cause for their penile deformity (see attached figure, p<0.001). Results from the CCH predictive algorithm similarly demonstrated the ability to predict men who had greater or lesser improvements to CCH injections (25-, 40-, or 49-degree median improvements for CCH gene scores 1-3, respectively, p<0.001). Hourglass/indentation was also correlated, with men who exhibited Allele G for SNP1 demonstrating a 2.3-fold higher relative risk for the finding (p=0.01). Other notable associations included specific genetic findings associated with plaque calcification (p=0.02), erectile dysfunction (presence, and self-reported strength of nocturnal erections, both p<0.01), and low testosterone symptoms (motivation, weight-gain, decreased libido; all p<0.01). Conclusions The PeyroniesGene test demonstrates several notable correlations with PD, erectile function, and low-testosterone related symptoms, including the ability to potentially predict outcomes to CCH therapy. External validation is warranted. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: PathRight Medical

Abstract Introduction Since FDA approval of Collagenase Clostridium Histolyticum 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. We therefore sought to compare key outcomes between the two therapies. Objective To compare the satisfaction and adverse event profiles between surgery and Collagenase Clostridium Histolyticum injections for the treatment of PD. Methods A randomized, controlled trial is ongoing. Participants were randomized 1:1 to receive either Collagenase Clostridium Histolyticum + traction (RestoreX) + sildenafil (CCH) or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD (Surgery). Objective, standardized, and non-standardized assessments were obtained at baseline and 3, 6, 12, 24, 36, 48, and 60 months post-treatment. Key outcomes included differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Results A total of 40 men were randomized with 36-month data available in 23. Mean age was 54.7 years, PD duration 37.4 months (mo), composite curvature 73.1 degrees (deg), and penile length 12.7 cm. All baseline variables were similar between cohorts. Regarding primary outcomes, consistent with earlier reports, at 36-months post-treatment, CCH men were more likely to report being very satisfied with treatment (54% vs 8%, p<0.01). For secondary outcomes, only questionnaire data were captured at three years without objective measurements obtained. No differences were noted between groups regarding subscales of the IIEF, PDQ, Beck’s Depression Inventory, SEP-2, SEP-3, sensation, or satisfaction with curvature. Surgery men reported higher subjective rates of length loss compared to CCH (92% vs 46%, p<0.001). Adverse events were similar between groups, with the exception of surgery men reporting higher rates of current pain (42% vs 8%, p=0.04), or decreased/abnormal sensation (45 vs 27%, p=0.03). Both groups indicated similar willingness to undergo the therapy again (75-77%). Interestingly, at 3-years, 42% of Surgery men said that their initial preference for treatment was surgery, which decreased from a peak 86% at 1 year and 55% at 2 years. However, in reviewing baseline information, only 28% of Surgery men actually preferred surgery at study onset, highlighting a significant but declining recall bias towards whatever treatment one actually ended up receiving. Conclusions Preliminary data suggests that when compared to surgery at 24-months, men receiving the treatment option including CCH were more likely to be very satisfied with therapy and reported having greater subjective length improvements and lower curvature recurrence rates. 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 Collagenase clostridium histolyticum (CCH) injections are a commonly utilized treatment for Peyronie’s disease (PD) in the United States. Although CCH is an established therapy, there is ongoing debate regarding the optimal timing of its administration. Specifically, it remains uncertain whether initiating treatment during the acute phase of PD results in different clinical outcomes compared to starting therapy in the chronic phase. Objective This study aimed to evaluate the efficacy and safety of CCH treatment in patients with Peyronie’s disease, assessing whether outcomes differ between those treated during the active phase versus the stable phase of the condition. Methods We performed an IRB-approved, retrospective analysis of 210 patients with PD. Patients were categorized by disease phase-active (n=59) which refers to the stage where the disease is actively progressing often accompanied by pain and change in curvature or stable (n=151) which refers to the stage where the curve is not changing for at least 3 months-and by curvature severity: Grade 1 (<30°, n=11), Grade 2 (30–60°, n=160), and Grade 3 (>60°, n=39). Demographic data and clinical outcomes (including calcification, bruising, swelling, pain, and surgical intervention) were collected and compared using chi-square and t-tests. Results The mean age of the cohort was 58.1 ± 8.1 years. The majority of patients were White (81.0%). Comparisons between active and stable phases revealed no statistically significant differences in the rates of calcification (61.0% vs. 55.0%, p=0.4446), bruising (36.2% vs. 44.8%, p=0.3342), swelling (19.0% vs. 29.0%, p=0.1976), pain (27.6% vs. 25.0%, p=0.8395), or surgical intervention (8.6% vs. 15.0%, p=0.3279). Patient-reported improvement was similar between the groups (55.9% vs. 59.6%, p=0.8660), as was the change in penile curvature (−12.1° vs. −11.0°, p=0.7398). These findings suggest that disease activity status alone does not significantly influence patient outcomes. When stratified by curvature severity, patients with Grade 3 curvature exhibited the greatest mean curvature improvement (−30.06°), compared to −7.82° in Grade 2 and +4.55° in Grade 1 (p<0.0001). Patient-reported improvement was also significantly more common in those with higher curvature severity: 61.5% in Grade 3 compared to 60.0% and 27.3% in Grades 2 and 1, respectively (p=0.0002). Interestingly, bruising was more frequent in patients with milder curvatures, with 88.9% in Grade 1 compared to 39.7% in Grade 2 and 42.1% in Grade 3 (p=0.0149). No other outcomes significantly differed across curvature grades. Conclusions Clinical outcomes in PD did not significantly differ between active and stable disease phases. These findings suggest consistent complication and treatment patterns regardless of disease stage. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Marius, Besins

Abstract Introduction Peyronie’s disease (PD) commonly presents with penile curvature, with potential influences from hand dominance on curve laterality. Objective This study investigates the relationship between hand dominance and curve laterality in PD patients and evaluates secondary outcomes including degree of curvature, treatment-related complications, and curvature change following collagenase Clostridium histolyticum (CCH, Xiaflex) therapy. Methods A retrospective review was performed on 112 PD patients stratified by hand dominance: right (n=102), left (n=7), and ambidextrous (n=3). The primary outcome compared hand dominance to curvature laterality. Secondary outcomes included baseline curvature degree, incidence of post-Xiaflex complications (bruising, swelling, pain, hematoma, fracture), and curvature improvement post-treatment. Multinomial logistic regression was applied to adjust for potential confounders. Statistical significance was defined as p<0.05. Results Median age at presentation was similar across groups (right: 59 years [IQR 54–63], left: 55 years [49–60], ambidextrous: 68 years [67–72], p=0.067). Among right-handed patients, curvature laterality was dorsal in 47% (n=47), left-sided in 26% (n=26), right-sided in 10% (n=10), and ventral in 6% (n=6). Left-handed patients demonstrated predominantly dorsal curvature (71%, n=5) and ventral curvature (14%, n=1). Ambidextrous patients had 67% dorsal (n=2) and 33% left-sided curvature (n=1) (p=0.796). Baseline median curvature degree was comparable: right-handed 43° (IQR 35–50), left-handed 40° (30–35), ambidextrous 40° (40–60) (p=0.829). Post-treatment adverse events were infrequent and did not differ significantly by hand dominance (all p>0.6). Although unadjusted analysis suggested a higher rate of new erectile dysfunction in left-handed patients (14.3%), this association was not statistically significant after multinomial regression adjustment. Median degree of curvature improvement following Xiaflex was 20° (IQR 15–30) in right-handed, 13° (0–20) in left-handed, and 30° (25–35) in ambidextrous patients (p=0.184). Conclusions Hand dominance does not appear to significantly influence penile curve laterality, baseline curvature severity, or treatment response in Peyronie’s disease. Xiaflex is a safe and effective treatment across hand dominance categories, with no increased risk of complications or erectile dysfunction after adjusting for confounders. Further studies with larger cohorts are warranted to confirm these findings. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast, Clarus Pharmaceuticals, Acerus Pharma; Endo Pharma.