Peyronie's Disease Research Articles

Temporal gene signature of myofibroblast transformation in Peyronie's disease: first insights into the molecular mechanisms of irreversibility.

Transformation of resident fibroblasts to profibrotic myofibroblasts in the tunica albuginea is a critical step in the pathophysiology of Peyronie's disease (PD). We have previously shown that myofibroblasts do not revert to the fibroblast phenotype and we suggested that there is a point of no return at 36hours after induction of the transformation. However, the molecular mechanisms that drive this proposed irreversibility are not known. Identify molecular pathways that drive the irreversibility of myofibroblast transformation by analyzing the expression of the genes involved in the process in a temporal fashion. Human primary fibroblasts obtained from tunica albuginea of patients with Peyronie's disease were transformed to myofibroblasts using transforming growth factor beta 1 (TGF-β1). The mRNA of the cells was collected at 0, 24, 36, 48, and 72hours after stimulation with TGF-β1 and then analyzed using a Nanostring nCounter Fibrosis panel. The gene expression results were analyzed using Reactome pathway analysis database and ANNi, a deep learning-based inference algorithm based on a swarm approach. The study outcome was the time course of changes in gene expression during transformation of PD-derived fibroblasts to myofibroblasts. The temporal analysis of the gene expression revealed that the majority of the changes at the gene expression level happened within the first 24hours and remained so throughout the 72-hour period. At 36hours, significant changes were observed in genes involved in MAPK-Hedgehog signaling pathways. This study highlights the importance of early intervention in clinical management of PD and the future potential of new drugs targeting the point of no return. The use of human primary cells and confirmation of results with further RNA analysis are the strengths of this study. The study was limited to 760 genes rather than the whole transcriptome. This study is to our knowledge the first analysis of temporal gene expression associated with the regulation of the transformation of resident fibroblasts to profibrotic myofibroblasts in PD. Further research is warranted to investigate the role of the MAPK-Hedgehog signaling pathways in reversibility of PD.

(372) Clinical Understanding Through Real-World Data to Validate Effectiveness of Treatments in Peyronie’s Disease (CURVE-PD): Registry Design

Abstract Introduction Limited information is available on the treatment modalities, treatment choices and outcomes of patients with Peyronie’s disease (PD). Clinical Understanding through Real-world data to Validate Effectiveness of treatments in Peyronie’s Disease (CURVE-PD) is a prospective longitudinal, multi-center, web-based PD registry, built on the healthie™ platform, that collects relevant real-world information from treating sites, and individuals with PD and their partners and clinicians. Objective The overarching primary objective is two-fold. First, the registry aims to collect real-world data on treatments used for PD (including injectables and any surgical techniques) to understand treatment choice and variability in treatment delivery, and to assess treatment effectiveness. Secondly, to understand the impact of treatments on patient-reported outcomes (PROs) and their partners’ satisfaction as well. Furthermore, the registry also recognizes the importance of evaluating the natural progression of Peyronie’s disease (PD) in men who choose not to pursue active treatment and instead opt for observational approaches. Methods Eligible adults (≥18 years of age) with a confirmed clinical diagnosis of PD who received PD treatment starting at or within 2 weeks before enrollment (“treated”) or have never received PD treatment (“untreated”) are invited to participate by registry site personnel or their treating physician. Untreated patients who initiate PD treatment after enrollment may crossover into the treated group. Using a web-based portal, which is part of the registry, participants complete surveys at enrollment, and, for those who are treated, longitudinally at treatment initiation and at 3- 6-, 9- and 12-months post treatment initiation. Participant surveys include validated PROs such as the Peyronie’s disease questionnaire (PDQ) scale, Peyronie’s disease questionnaire for female sexual partners (PDQ-FSP), international index of erectile function (IIEF) for participants and male sexual partners, patient health questionnaire-9 (PHQ-9), and the Beck anxiety index (BAI). Additionally, participants are asked to provide details on sexual function, and reasons for treatment start and satisfaction with treatment. Designated site staff use the clinician web-based portal to enter information on demographics, medical history, and treatment history for up to 12 months before enrollment. Prospective data collected include information on PD treatments and clinical assessments as performed in routine clinical care (e.g., pre-treatment and post-treatment penile characteristics and PD symptoms) at enrollment, baseline, and each clinical visit. Currently, 15 sites in the United States are planned, with a possible future expansion to additional sites. The target for enrollment in the treated group is a minimum of 1,000 patients with PD. Results CURVE-PD enrollment opened in June 2023, with an anticipated 15 U.S. sites being enrolled over the next few months. Initial data for analysis are anticipated to be available in 2024. Conclusions CURVE-PD is a novel registry where participants with PD and their partners can provide information on quality-of-life impacts in a secure and private evidence generation web-based environment, that links both patient and clinician-reported treatments and assessments. This registry will provide the means for investigating real-world data (RWD) to attain real-world evidence (RWE) for more comprehensive knowledge and evaluation of the natural history, treatment patterns and modalities, and the comparative effectiveness of treatments for PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals 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 Pharmaceuticals Inc.

(012) Incidence of Peyronie’s Disease After Radical Prostatectomy Among Patients Undergoing Penile Rehabilitation Regimen

Abstract Introduction Radical prostatectomy remains one of the gold standard treatments for localized prostate cancer, the most prevalent solid organ cancer in men. Surgical management of prostate cancer has been theorized to increase the risk of developing Peyronie’s Disease (PD). In 2010, Drs. Tal and Mulhall’s team characterized the incidence of PD in a cohort of 1011 men after radical prostatectomy to be 13.7% at 2 years and 15.9% at 3 years of follow-up. These numbers, significantly higher than estimates in the general population, which range from 0.5 to 7.1% (Sharma et al., Sex Med Rev 2020;8:314–23), suggest radical prostatectomy is a risk factor for developing PD. Objective Our aim was to evaluate the incidence of PD among post-prostatectomy patients who undergo a formal multi-modal penile rehabilitation program that includes mechanical and pharmacologic interventions to promote penile smooth muscle activation after surgery. Methods In this retrospective, descriptive study we reviewed the charts of 581 patients who were diagnosed with prostate cancer, treated with robot-assisted laparoscopic radical prostatectomy (RALP), and were engaged in a penile rehabilitation program from January 2016 through January 2019. At our institution, patients scheduled for prostatectomy are referred preoperatively to an academic Men’s Health clinic to start a multi-modal program and follow up regularly for evaluation of sexual health. The program includes daily tadalafil, L-citrulline, and VED use (Table 1). Patients refractory to these therapies had the option to increase tadalafil dosing or undergo further treatment with intracavernosal injections at ~3 months post-op. We excluded patients who had PD pre-operatively or who did not have post-operative follow-up with the providers at this institution. The primary outcome of interest was the incidence of PD among this cohort. Secondary outcome included time to development or diagnosis of PD. Results 581 patients with prostate cancer treated with RALP engaged in penile rehabilitation and were included in this analysis. The median age of men was 62.6 y with additional demographics listed in Table 2. The incidence of PD in this cohort was 2.9% (17 patients) with a median follow-up of 21.4 mo (IQR 2.8 – 55.8 mo). The diagnosis of PD was made at a median of 28.7 mo (IQR 20 – 36 mo) after prostatectomy. The 17 patients with PD had a median follow-up of 38.9 mo (IQR 23.2 – 55.8 mo). Conclusions In this cohort of prostate cancer patients treated with RALP and undergoing a consistent, multi-modal penile rehabilitation program, the incidence of PD was 2.9%, and median time to diagnosis was 28.7 months. This is the first study to assess PD incidence in men who engage in mechanical and pharmacologic penile rehabilitation at time of RALP. Furthermore, diagnosis of PD was made more than two years after surgery; this warrants further evaluation on whether penile rehabilitation prevents PD. This retrospective analysis is a hypothesis-generating study that should inspire further research on the role of regular mechanical stimulation or daily PDE-5 inhibitors in delaying or preventing PD after pelvic surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Scientific.

(401) Treatment Utilization and Temporal Trends in Peyronie’s Disease: A Retrospective Analysis of an Insurance Claims Database

Abstract Introduction The current treatment algorithm for Peyronie’s Disease (PD) was updated in 2015 to exclude oral therapies. Non-surgical pharmacological management is now limited to intralesional therapy with Collagenase Clostridium Histolyticum (CCh), Interferon, or Verapamil. Surgical options include tunical plication, plaque incision/excision with or without grafting, and penile prosthesis surgery with or without adjunctive procedures. An understanding of trends in management of PD since the updated guidelines is limited. Objective Our objective is to assess treatment utilization and temporal trends in PD with the change in guidelines. Methods We conducted a retrospective review of men with PD using data in the IBM MarketScan insurance claims database. Patients were identified using ICD 9/10 codes and treatments were identified using J and CPT codes. Only patients aged ≥18 years with at least 1 year before and after a PD diagnosis were included in the analysis. Descriptive statistics were used to describe non-surgical and surgical treatment groups. Linear regressions were also performed to assess the trends of each year based on initial PD treatment. Results Between 2011-2019, we identified a total of 45,114 patients with a diagnosis of PD. Overall, while the majority (91.9%) chose conservative management with no intervention, 1,041 (2.3%) pursued intralesional therapy and 2,594 (5.8%) pursued surgical intervention as an initial treatment option. Among the patients who initially opted for intralesional therapy, 67 (6.4%) sought subsequent surgical treatment whereas 974 (93.6%) did not pursue additional treatment. In comparison, 116 (4.5%) patients who initially underwent surgical intervention sought subsequent treatment with the remaining 2,478 (95.5%) not pursuing additional treatment. Annual overall treatment rates increased from 7.2% to 8.1%. There was a statistically significant increase in the utilization of intralesional therapies from 0.3% in 2011 to 4.1% in 2019 (p=0). Surgical interventions significantly declined from 6.8% to 3.9% over the same time period (p=0.004). Conclusions The present study demonstrates that PD treatment trends have changed over time. With overall low secondary treatment rates for patients initially pursuing either non-surgical or surgical treatment options, a greater proportion of patients are initially pursuing less invasive, non-surgical treatment options with intralesional therapy over time. These findings emphasize the dynamic nature of treatment decisions and contribute to a deeper understanding of the treatment landscape that can be incorporated into patient counseling. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Paterna bio, Firmtech, Turtle health, Maximus, Carrot, Contraline, endo pharmaceuticals, inherent biosciences, techfields inc, macro trials, alto neurosciences, curebase, vivify medical.

(286) Gender Disparities Exist in the Surgical Management of Peyronie's Disease and Urologic Prosthetics: An Evaluation of American Board of Urology (ABU) Surgical Case Logs

Abstract Introduction Urology has been predominantly male-dominated, although recent trends indicate increased female representation among urology residents, physicians and advanced-practitioner providers. While progress has been made, gender disparities persist due to societal perceptions and biases. The goal of this study was to investigate whether a provider gender gap exists in the field of reconstructive urology using American Board of Urology (ABU) case logs. Objective To examine case volume characteristics for provider gender disparities in Peyronie’s disease and urologic prosthetic surgery. Methods Retrospective review of surgical case log data from 2003 to 2023 of certified urologists was performed for 11 Current Procedural Terminology (CPT) codes for the surgical management of Peyronie’s disease (penile plication CPT 54360, plaque excision/incision with grafting CPT 54111, 54112), male urethral sling or artificial urinary sphincter (CPT 53440, 53445), and placement of penile implant (CPT 54400, 54401, 54405). Inclusion criteria included male patients who were 18 years old or older. Data collected included patient and surgeon demographics, surgical procedure, and surgeon fellowship training status. Cases were analyzed using descriptive statistics and regression testing. Results From 2003 to 2023, a total 2,852 urologists performed 15,171 Peyronie’s disease and urologic prosthetic surgical procedures. Among these procedures, 1,910 (13%) Peyronie’s disease, 8,940 (59%) penile implant, and 4,321 (28%) incontinence procedures were identified. Out of the total practicing urologists, 2,626 were male and 226 were female; the distribution of cases revealed 5 cases performed per male surgeon and 4 cases per female surgeon. Over two decades, there was a significant positive trend in the proportion of cases performed by female surgeons (p < 0.001). 169 (6%) surgeons completed fellowships in Andrology or Male Reconstruction, and performed 2,129 (14%) of total procedures. Across surgeons with Andrology or Male Reconstruction fellowship-training, there were 13 cases performed per male surgeon and 7 cases per female surgeon. Conclusions Our study confirms underrepresentation of female surgeons in the field of Peyronie's disease and prosthetic urology. Although there is a trend of increasing female representation over time, further research can be done to identify barriers to gender equality in the field. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast.

(171) The Effects of Pretreatment with Xiaflex on Penile Curvature Correction with Manual Modeling During and After IPP placement

Abstract Introduction There are a variety of treatment modalities available to treat Peyronie’s disease (PD), including collagenase clostridium histolyticum (Xiaflex) injections. Patients with concomitant erectile dysfunction (ED) and PD are best served by insertion of an inflatable penile prosthesis (IPP) in order to adequately treat both conditions. Many PD patients may undergo other PD treatments, including Xiaflex, prior to IPP implantation. There are multiple methods of curvature treatment during IPP surgery, and manual modeling is the predominant method in our practice. Little data exists regarding whether Xiaflex treatments prior to IPP placement influence changes in penile curvature during and after IPP surgery with manual modeling. Objective The primary objectives were assessing the impact of pre-treatment with Xiaflex on penile curvature immediately after IPP implantation and after manual modeling. The secondary objective was change in penile curvature post-operatively. Methods All IPP patients with known preoperative penile curvature with and without a history of Xiaflex injections undergoing IPP placement by a single surgeon from January 2017 to June 2023 were included in this IRB-approved (IRB 00031589) retrospective series. All patients had a 3-piece Coloplast Titan Touch IPP (Coloplast, Minneapolis, MN, USA) ranging 16-24cm in length (mean 19.8 ± 1.9cm) with 0-3cm rear tips (mean 1.4 ± 0.9cm). Goniometer was used to assess curvature during preoperative intracavernosal injection and duplex Doppler ultrasound, at multiple points intraoperatively, and postoperatively at 2 weeks, 6 weeks, and 6 months. Biplanar curvatures were recorded as primary and secondary values. SPSS (IBM, Armonk, NY, UA) was used for statistical analyses, which included t-tests, chi-squared tests, and ANOVA. Results Sixty-one patients were included. Preoperative curvature was 35° ± 17° (10° to 70°) for the Xiaflex cohort (n=11) and 41° ± 15° (20° to 80°) for the Xiaflex naïve cohort (n=50). At the time of IPP placement, patients previously treated with Xiaflex had a 19° ± 12° absolute reduction in primary penile curvatures, corresponding to a 45% ± 36% improvement (25° reduction to 5° worsening), while Xiaflex naïve patients had a 20° ± 13° absolute reduction and 54% ± 23% improvement (50° reduction to no change). Similar mean curvature reductions were seen with IPP placement in primary dorsal curves in the Xiaflex cohort (n=7, 21° ± 4°, 51% ± 12%, 25° to 15° reduction) and Xiaflex naïve cohort (n=24, 21° ± 9°, 51% ± 22%, 40° to 5° reduction). There was little difference in change in curvature after modeling between the Xiaflex (11° ± 3°, 63% ± 23%, 15° to 5° reduction) and Xiaflex naïve patients (14° ± 9°, 70% ± 20%, 40° reduction to 5° worsening). Interval assessments postoperatively were also comparable. Sample size precluded assessment of statistical significance among groups. Conclusions Preoperative treatment of PD with Xiaflex does not impede nor significantly improve curvature correction with IPP implantation and manual modeling. Similar changes in penile curvatures were seen in both groups regardless of curvature direction, modeling, or postoperative interval. In patients with severe PD, Xiaflex may be a useful tool to improve preoperative penile curvatures such that they may be more easily correctable with an IPP. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, MenMD.

(399) Reducing Out-of-Pocket Expenses for Peyronie’s Disease Therapy with a Novel Penile Traction Device

Abstract Introduction Penile traction therapy (PTT) has gained popularity as a nonsurgical approach to penile lengthening and curvature correction in those with Peyronie's disease (PD). PD is an acquired fibrotic plaque that develops within the tunica albuginea and causes penile curvature, which can have significant physical and mental health consequences. Due to the sensitive nature of this disease presentation and the large number of unidentified or misdiagnosed people, current prevalence estimations in the US are around 11%. PD therapies aim to correct penile curvature while also addressing erectile dysfunction and pain. Common PD therapies include oral medications, intralesional penile injections, surgery, and stretching techniques. When deciding which therapies to pursue, disease severity, costs, compliance, and patient access to facilities and trained providers must be considered. Of these therapies, PTT with a penile traction device (PTD), although uncovered by insurance, has proven to be one of the most cost-effective PD treatments. While an effective treatment in some men, PTDs cost hundreds of dollars out-of-pocket. Objective Our project aims to address the financial and practicality concerns of penile traction therapy by creating an affordable and comfortable PTD. Methods Our PTD offers precise, dial-adjustable tensioning and penile holding systems with contoured penile holding plates lined with silicone cushions for improved grip and comfort. Our PTD is 3D-printed using polylactic acid (PLA) and medical-grade silicone. To assess our efforts in improving comfort, we measured holding capacity under tension at increasing amounts of penile clamping. We compared our silicone-lined clamp to an all-plastic clamp: this test served as a surrogate for comfort. By improving its grip on the penis, patients can secure their penis with minimal clamping force, thereby improving comfort. Results Our literature search revealed that the average cost for PTDs recommended by urologists for patients with PD was approximately $883. Our PTD currently costs $6.38 to manufacture and assemble. We found a statistically significant (p=0.000276) increase in the tension-holding capacity of the silicone-lined clamp compared to that of the all-plastic clamp. This demonstrates that our silicone-lined clamp may exert less clamping force on the penis, thereby providing patients with the same stretching and a more comfortable grip. Conclusions Future directions include exploring urologists' perception of PTT for PD and their PTD recommendation patterns, refining our current PTD model, and clinically testing our device compared to those currently available. Disclosure No.

(114) Mathematical Model for Peyronie's Disease

Abstract Introduction Peyronie's disease may affect up to 20% of men worldwide. After the curvature, penile length loss is the most common complaint. The severity of the curve angle is associated to with penile length and volume loss. Objective Create a theoretical mathematical formula to help clinicians and patients to estimate the penile length and volume loss in patients with Peyronie's Disease. Methods Applying Euclidean Trigonometric principles an geometric axioms a mathematical formula was created. Inserting measurements that are commonly retrieved from patients with Peyronie's disease, i.e., Penile girth, length, and curvature angle in the formula, a 2-d dimensional triangle is created. Applying the torus equation the arc length and angular deviation is found and the the penis volume and lenght loss can be calculated. Results A mathematical formula to evaluate the penile volume and length loss was created accounting for the deviations in the penile geometry occuring in patients with monoplanar and multiplanar Peyronie’s disease deviations. Conclusions This formula provides a mathematically accurate method to predict potential loss of penile length and volume in patients with monoplane or multiplanar Peyronie's disease. The model can be an additional tool for advising patients between shortening or lengthening procedures and help physicians and patients set expectations for results after surgical procedures. Disclosure No.

(245) Surveying the Genomic Landscape of Peyronie's Disease: A Study of 22 Cases

Abstract Introduction Since its description in 1743 by François de la Peyronie, penile fibromatosis continues to present an elusive pathogenesis. One of its distinguishing characteristics is the excessive proliferation of fibrogenic myofibroblasts, resulting in the formation of dense fibrous plaques that disrupt the normal cytoarchitecture of the tunica albuginea, giving rise to penile abnormalities. The possible clonal nature of the disease has been investigated by many studies and some have identified occasional karyotypic abnormalities, most commonly involving chromosomes 7, 8, 17, 18, X and Y (Mulhal JP et al 2004). Objective This study aimed to comprehensively analyze the genomic landscape of Peyronie's disease in a significant number of cases using a whole genome copy number variation assay (CNV). The objective was to identify any recurrent chromosomal gains or losses that could shed light on the pathogenesis of this disease, including the potential identification of an underlying clonal process. Methods Thirty-nine surgical specimens were retrospectively examined from men diagnosed with Peyronie's disease, collected between 1992 and 2022 (median age: 56 years, range: 17-73). The study was conducted under the approval of the Institutional Review Board (IRB # 22-006924). Tissue samples were fixed in 10% buffered formalin, embedded in paraffin, and subsequently subjected to histologic review and DNA analysis. DNA extraction followed standard protocols. Among the samples, 22 contained high-quality material suitable for CNV array analysis using the OncoScan SNV array, which encompassed approximately 900 genes/loci with a resolution of 50-125 kb. Additionally, the array included a somatic mutation panel targeting nine cancer-related genes. Results No significant loss or gain of chromosomal material was identified in the twenty-two cases analyzed. However, the somatic mutation panel revealed potential unconfirmed DNA mutations in NRAS, EGFR, and TP53. Ongoing studies are being conducted to confirm these mutations. Conclusions The etiology and pathogenesis of Peyronie's disease remain unresolved, presenting a challenging area of research. However, the findings of this study provide evidence that major recurrent losses or gains of chromosomal material are unlikely to play a significant role in the pathogenesis of this disease. While shedding light on this aspect, it is crucial to acknowledge that further research is necessary to confirm and expand upon these initial observations. Disclosure No.

(398) The Correlates of Satisfaction with Long-term Outcomes Following Collagenase Clostridium Histolyticum Treatment for Peyronie’s Disease

Abstract Introduction Collagenase Clostridium histolyticum (CCH) is the only FDA-approved medication for Peyronie’s Disease (PD) in the United States. Roughly half of patients who received CCH experienced improvements in curvature by more than 20% in the IMPRESS I/II trials. Despite objective improvements in PD severity, some patients still report dissatisfaction with CCH treatment. The effects of subjective reasons of greatest satisfaction and dissatisfaction on long-term overall treatment satisfaction is even less clear. Objective The aim of this study was to assess how subjective patient responses regarding reasons for satisfaction and dissatisfaction correlate to long-term satisfaction with CCH treatment. Methods An Institutional Review Board approved retrospective chart review and standardized questionnaire was conducted for all patients with PD who received CCH from 2009-2022. Patients who received CCH before presenting to our institution were excluded. The questionnaire utilized the Treatment Satisfaction Questionnaire for Medication (TSQM), which is validated across the subdomains of satisfaction with effectiveness, side effects (SE), convenience, and global satisfaction (GS), and summed to generate the TSQM total score. The questionnaire also included multiple-choice questions on CCH insurance coverage, reasons for greatest satisfaction and dissatisfaction with a free-response “other” answer choice, and likelihood of recommending CCH to other patients with PD on a scale from 0-6. Statistical analyses were performed in R using Wilcoxon rank sum test and independent T-test to compare continuous variables with TSQM scores, Spearman’s rank correlation to compare categorical variables with TSQM scores, and Fisher's exact test to compare categorical variables with one other. Results Of the 243 eligible patients, 80 (32.9%) responded (Table 1). Of these, 34 (42.5%) reported satisfaction with CCH treatment. On average, surveys were completed 4.7 (SD 2.3) years after last CCH injection. When queried on what factors patients were the most satisfied with, improvements in curvature and sexual function were significantly correlated with increased scores in the effectiveness subdomain, GS subdomain, and TSQM total (p<0.01 for all) (Table 2). 30 (37.5%) patients self-reported no satisfaction because of no perceived improvement in the same question, which significantly correlated with decreased scores in the effectiveness subdomain, GS subdomain, and TSQM total (p<0.0001 for all). Of this cohort, 26 (86.7%) patients would not recommend CCH to other patients with PD (OR 10.27, 95% CI 2.94-46.85, p=0.00002). When queried on what factors patients were the most dissatisfied with, pain with injection, duration of CCH series, and no improvements in curvature were all significantly associated with lower scores in effectiveness subdomain, GS subdomain, and TSQM total (p<0.003 for all). Patients with insurance coverage had lower odds of reporting cost of CCH as their greatest dissatisfaction (OR 0.05, 95% CI 0.004-0.62, p=0.03). Conclusions Our data suggests that the most important factors for long-term patient satisfaction with CCH treatment are improvements in curvature and sexual function while the most important factors for patient dissatisfaction are pain with injection, duration of CCH series, and no improvements. While pain with injection is temporally brief, it continues to negatively affect patient satisfaction even years after completion of CCH. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: M.K. acts as a consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast. M.K. is an investor of Sprout. L.L. acts as a consultant for AbbVie, Aytu BioScience, Contraline, Lipocine. L.L. acts as an advisor for Inherent Bioscences. L.L. acts as consultant/speaker for Endo Pharmaceuticals. L.L. acts as a speaker for American Medical Systems/Boston Scientific.

(116) Breaking the Silence: Should I Be Concerned About Penile Fracture when Injecting Collagenase Clostridium Histolyticum?

Abstract Introduction Collagenase clostridium histolyticum (CCH) was first approved by the FDA in December 2013 for the nonsurgical management of Peyronie’s disease (PD) in men who are otherwise healthy. Penile fracture (PF) is a rare but concerning adverse event with known association with CCH administration. Objective To determine the risk of PF in men with PD who are receiving CCH and correlations between the risk of PF and comorbidities previously excluded in studies investigating the safety of CCH, namely the IMPRESS trial. Methods The TriNetX database was used to measure the rate of hospital visits for penile fracture using the ICD-10 code S39.840A. Results were limited to patients who were diagnosed with PD (ICD-10 N48.9) and were seen between July 2013 to July 2023. Patients were excluded if they had a history of surgical intervention for PD, including plaque excision and grafting, penile plication, and insertion of inflatable penile prosthesis. An odds ratio (OR) was calculated to compare the rates of PF between patients who had and had not received CCH. For those who received CCH, OR’s were calculated to determine if the presence of certain comorbidities increased the risk of PF. Results Within the examined time period, 44,542 patients with PD experienced 280 PF’s. The rate of PF in those who had and had not received CCH were 1.25% (N = 37) and 0.59% (N = 243) respectively, OR 2.122 (95% CI: 1.499-3.001, p<0.0001). Tobacco use, diabetes mellitus, peripheral vascular disease, hypertension, hyperlipidemia, erectile dysfunction, and hypogonadism were not associated with an increased risk of PF in men receiving CCH (p>0.05) (Table 1). Conclusions While the rate of PF following CCH use for PD was low at 1.25%, this was significantly higher than in those who did not receive CCH. Despite this, men who were previously excluded from studies examining the safety of CCH use for PD due to comorbidity burden were without an increased rate of PF, suggesting that these men may be able to receive CCH without additional risk of PF. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma, Clarus Therapeutics, Coloplast.

(112) Efficacy and Safety of Platelet-Rich Plasma Injections for Peyronie’s Disease: A Randomized Double-Blind Placebo-Controlled Cross-Over Study

Abstract Introduction Peyronie's Disease (PD) is currently treated with intralesional collagenase injection, the only FDA-approved medical therapy. Platelet-derived therapies, such as autologous platelet rich plasma (PRP), have shown potential in tissue regeneration. We are investigating the safety and efficacy of PRP in PD with an ongoing randomized, placebo-controlled, crossover study. Objective The objective of this study is to assess the safety and efficacy of autologous platelet-rich plasma (PRP) treatment in Peyronie's Disease (PD) through a randomized, placebo-controlled, crossover trial. Methods We analyzed data from an ongoing trial conducted between April 2021 and June 2023. Men with PD (write degrees/dorsal only etc) were randomly assigned to receive two 0.5 ml injections of PRP obtained using an autologous platelet separator (Arthrex Angel, Arthrex Inc.) or placebo directly into the dominant plaque, with a two-week interval between injections. Immediate post-procedure assessments included Visual Analogue Pain Scale, and follow-up evaluations focused on identifying complications. After three months, participants crossed over to the other treatment arm for two additional injections. Goniometer measurement assessments were performed prior to each crossover (NCT04512287). Related Samples Wilcoxon-Signed Rank test was used for dependent repeated groups, the serial measurements of degree of curvature at different time points for each patient within a specific group. Findings at p< 0.05 were considered statistically significant. Results The analysis includes data from 29 men who completed all injections and the 6-month follow-up. No minor or major adverse events, such as penile bruising, swelling, edema, allergy, or penile fracture, were reported. Regarding efficacy, we observed a significant reduction in curvature after six months compared to baseline. The pretreatment median curvature was 40.0 (IQR: 15), the median post-treatment curvature 30.0 (IQR: 30) (p=0.014). Furthermore, we did not observe worsening of curvature in subsequent evaluations. Conclusions Our findings from our ongoing clinical trial suggest that PRP treatment for Peyronie's Disease is safe, with minimal adverse events reported. The preliminary efficacy data indicates a significant reduction in curvature after 2 injections each of placebo and PRP treatment compared to baseline. Nevertheless, study completion is necessary prior to reporting true efficacy data comparing PRP vs placebo. Disclosure No.

(278) Peyronie's Disease Among Men Who Have Sex With Men: Perceptions, Characteristics, and Psychosocial factors

Abstract Introduction Peyronie’s Disease (PD) is a condition characterized by the development of fibrous scar tissue causing penile curvature and often painful erections. From a sexual health perspective, PD is commonly researched in heterosexual men; however, there is a paucity of data assessing the impact that PD has on men who have sex with men (MSM) population. Objective This prospective survey study sought to collect data on how PD affects MSM from a biopsychosocial and sexual perspective and compare this population’s experience with non-MSM. Methods An anonymous online survey was deemed IRB exempt and administered to the following online platforms: Reddit to include r/PeyroniesSupport, r/lgbtstudies, r/sex, and on Facebook to the Peyronie’s Disease Support group in July 2023. Participants were asked demographic info, sexual orientation, type of sexual intercourse, family history of PD, history of trauma, immune disease, PD symptoms, partner and self-bother, degree of curvature, care seeking, medical interventions, impact on mental health, disease progression, as well as the Peyronie’s Disease Questionnaire (PDQ) survey. Descriptive statistics were performed. Results Thirty-six men completed the survey, nine being MSM (11.8% “men and others” and 14.7% “strictly men"). Reported sexual interactions included anal (50%), vaginal (77%), and oral (79%) intercourse. History of penile trauma occurred in 32% of respondents. None of the respondents reported a family history of PD, and two subjects disclosed autoimmune diseases. The most common symptoms, experienced by 91% of subjects, were “shortening and/or narrowing of the penis,” followed by: erectile dysfunction (69%), difficulty with sexual intercourse (44%), painful erections (31%), and painful sexual intercourse or masturbation (28%). 85% of surveyed men and 100% of MSM stated PD negatively impacts their mental health. Assessment of partner satisfaction revealed women express greater disapproval (12%) compared to men (3%). The majority of men (91%) reported seeing a urologist with only 35% seeing one regularly and 50% being MSM. A negative experience with a urologist was reported in 40% of MSM and 20% of non-MSM. Degrees of reported curvature were: 77% with less than or equal to 45 degrees, 6% between 46-60 degrees, and 18% between 61-90 degrees. Greater than 60% and 27% were offered medical and surgical interventions, respectfully. 62% reported their PD has remained stable. Conclusions In conclusion, the results of this survey suggest that PD may have a greater negative effect on mental health and experience with a urologist for MSM. However, non-MSM are more likely to experience partner disapproval. Overall, the characteristics of PD do not grossly vary between MSM and non-MSM but the psychosocial aspect may possess greater consequences for MSM. More data is needed on this understudied population affected by PD. Disclosure No.

(395) Safety and Efficacy of Collagenase Clostridium Histolyticum in Peyronie's Disease Men with Ventral Curvatures

Abstract Introduction Limited data are available on the efficacy of collagenase clostridium histolyticum (CCH) on Peyronie’s disease (PD) in men with ventral curvatures. Our team previously published a limited series of outcomes of 25 men with ventral curvatures who underwent CCH. Given the paucity of data available, we sought to provide an updated series of outcomes in this important cohort. Objective To report outcomes of men undergoing CCH injections for PD based on initial direction of curvature, including absolute and percent improvement in curvature, adverse events (AE), and other subjective outcomes. Methods A prospective registry has been maintained of all men undergoing CCH injections since 2014. All men underwent curvature assessments and subjective questioning at the time of initial evaluation and prior to each subsequent series of injections. The method of injection and subsequent protocol have changed in a stepwise fashion since 2014 and currently include injecting 0.9 mg (diluted to 0.8 mL) on back-to-back days, injecting into the point of max curve with an erection on day 1, performing in-office modeling on day 2, utilizing Restorex traction beginning on day 2, and wrapping for 4-8 days depending on results. To review outcomes, clinicopathologic data were abstracted from the registry including relevant history, exam, and data obtained at the time of penile ultrasound and curvature assessment. Outcomes are reported using a “Most Recent” definition (most recent data point used, regardless if the patient continues or finished treatment) and “Completed 8 or Satisfied” (only included if the patient indicated that they were done with treatment or had finished the full 8 injections). Results A total of 560 patients (mean age 57 years) were identified from March 2014 through Feb 2023 and comprise our study cohort. Overall, 85 men had a ventral component to their curvature and 475 non-ventral. Baseline demographics and clinical factors were similar between groups, with the exception of penile length (ventral 14.0 cm, non-ventral 12.0 cm, p<0.0001), Psych and Physical subdomain of the Peyronie’s Disease Questionnaire (10 vs 12, p=0.03), and prior treatment with CCH (3% vs 16%, p=0.03). Following treatment, men in the ventral cohort exhibited possibly greater improvements in curvature (Most Recent Definition: -25 degrees vs -24, p=0.08; 45% vs 34%, p=0.03; Completed 8 or Satisfied Definition: -35 vs -25, p<0.05, 48% vs 38%, p=0.11). However, all other outcomes were similar between cohorts, including differences in subdomains of the IIEF and PDQ, use of traction therapy, and adverse events including ecchymoses, hematomas, and popping sensations. Importantly, no urethral complications were experienced in the ventral group. Conclusions Men with ventral PD may be effectively treated with CCH with similar AEs compared to other directions. Ventral curvatures are likely associated with greater overall curvature improvements compared to other directions. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo - Matt Ziegelmann.

(397) Investigating the Psychological Bother and Depression Among Gay Men with Peyronie's Disease

Abstract Introduction I: Peyronie's disease (PD) is associated with psychological bother, including depression and relationship dissatisfaction. Objective Our objective is to describe the prevalence of psychosocial issues using validated instruments, comparing gay and non-gay males. Methods We included patients diagnosed with PD who completed two validated questionnaires. The questionnaires were the Peyronie's Disease Questionnaire (PDQ) and the Center for Epidemiologic Studies Depression Scale (CES-D). The PDQ has 3 domains that evaluate psychological and physical symptoms, penile pain, and bother signs. Higher PDQ scores indicate a greater negative impact, and a score ≥ 9 on the bother domain indicates significant distress. A CES-D score ≥ 16/60 suggests clinical depression. All gay and non-gay patients were matched, and potential indicators of psychological distress were examined in both populations. Our multivariable analysis (MVA) models included age, sexual orientation, pain, and curvature. Additionally, we collected demographic information and PD-related characteristics. Results 74 individuals were matched based on age, curvature direction, and curvature degree: 37 gay and 37 non-gay. The median age was 57 (50, 62) years. Gay population characteristics: 60% were partnered; 54% had ≥ 2 comorbidities; median PD duration of 9 (4, 17) months; median curvature of 35 (29, 49) degrees; 66% had penile instability; 57% in a dorsal direction curvature, and 73% were located at the mid-shaft; 18% had multiplanar curvature. The PDQ scores in the gay vs. non-gay population: median score on psychological and physical domain of 10 (7, 18) vs. 11 (5, 16); median score on pain domain was 3 (0, 9) vs. 3 (0, 6), with 43% of the gay population with pain vs. 21% in non-gay; median score on bother domain was 8 (4, 10) vs. 8 (6, 11), with 65% of gay patients with significant bother (score ≥ 9) compared to 51% in non-gay. Regarding the CES-D scores, 38% of individuals in both populations demonstrated meaningful depression (score ≥ 16), with a median score of 12 (4, 19) in the gay population and a median of 12 (5, 23) in non-gay. In the MVA, sexual orientation was not a predictor for bother or depression (Table 1). Conclusions More than half of both groups had meaningful bother, and 1 in 3 had clinical depression; however, sexual orientation was not a predictor of bother or depression. Disclosure No.

(322) Predictors of Erection Reversal After Penile Doppler Ultrasound

Abstract Introduction Erection hardness (EH) is a physiologic response graded subjectively on the Erection Hardness Grading Scale during penile Doppler ultrasound (PDUS). Objective This study aims to gather data on the reversal rate following persistent EH sufficient for penetration or higher after PDUS and identify associated predictors. Methods The study population consisted of (i) men with poor response to PDE5i and ICI or (ii) who need curvature assessment due to Peyronie’s disease (PD), (iii) and underwent penile duplex Doppler ultrasound (PDUS), (iv) using a vasoactive agent redosing schedule were included and reviewed retrospectively. Patients with incomplete data were excluded. We performed a descriptive assessment of demographics and comorbidities, including a history of cancer, PD, depression, or anxiety. EH was evaluated by a sexual medicine-trained physician for each case and reported before and 30 minutes after PDUS. EH was assessed on a scale between 0 (no erection) to 10 (erection hard as a rock), with 6 being good enough for penetration. We also described the number of injections, the dose, and PDUS hemodynamic parameters, including peak systolic velocity (PSV) and end-diastolic velocity (EDV). Arterial insufficiency (AI) diagnosis was made with PSV values ≤25 cm/sec bilaterally and corpora veno-occlusive dysfunction (CVOD) with EDV values ≥5 cm/sec bilaterally. We also reported a reversal procedure rate performed due to persistent erection after PDUS, and predictors were assessed. Factors entered into the model included: patient age, EH for PDUS (8 or greater), and dose of vasoactive agent used (Table 1). A p-value ≤0.05 was considered statistically significant. Results 2439 individuals were included. The median age of 59 (50,67) years. 12% had diabetes, 13% reported ≥ 3 comorbidities, 44% had prostate cancer, 17% had a history of depression, and 14% had a history of anxiety. 44% described PD. The vasoactive agent used for PDUS was Trimix 86% and 14% others. The median dose used was 20 (10, 50), and the median of injections applied was 2 (1, 2). The EH median was 8 (6, 9) for PDUS, and 65% had an EH of 8 or greater. The PDUS diagnosis was normal in 62% of the patients; 8% had AI, 29% had CVOD, and 1% had AI+CVOD. The reversal procedure rate was 41%. In the MVA, significant predictors of erection reversal were higher vasoactive agent dose used, age 50 years or younger, and EH 8 or greater for PDUS (Table 1). Conclusions Erection reversal in our redosing PDUS was highly prevalent; predictors of reversal were younger age, greater EH for PDUS, and higher vasoactive agent dose. Disclosure No.

(117) Interrater Agreement and Feasibility of Three-Dimensional Photography for Curvature Assessment in Peyronie's Disease

Abstract Introduction Curvature assessment is an iterative aspect of the evaluation of Peyronie’s Disease (PD); its accuracy is subject to patient erection quality and clinician technique. Prior studies have shown promising results when using 3D modeling software in curvature assessment, yet none have applied the technology to human subjects with complex PD in an authentic clinical scenario. Objective To evaluate the feasibility of using 3D modeling to assess penile deformity in PD patients. Methods MirrorMe3D is a HIPPA-compliant iOS mobile and web-based platform designed for 3D anatomical modeling. 2 trained urology fellows (coders 1 and 2) were trained to create models using the app by acquiring ≥ 12 images of the target obtained in a multiplanar, 360-degree fashion. Participants verbally consented to deidentified penile photography during their clinic visit for penile curvature assessment with Doppler ultrasound (CADUS). Photographs were obtained prior to performing DUS with the patient in the supine position and using a commercially available clip-on ring light and custom 3D-printed holder device placed over the penis base for stabilization. 3D models were generated upon completion of the visit and screened for quality. Curvature assessment on the 3D images included curvature direction, location, degrees, and other defects identified via visual inspection of the digital model. Results 7 unique, quality 3D images were generated using 15-20 photos per participant (Figure 1). The time required to obtain images was 1-2 minutes. Once the 3D image was developed, the curvature assessment took about 5 minutes. Quantitative results are summarized in Table 1. We observed a high rate of agreement in terms of primary direction of curvature and an acceptable variance rate when evaluating degrees of curvature within a margin of 10°; of note, coders were in agreement with each other to within a 10° margin 100% of the time (7/7 patients). We also observed a high agreement rate when evaluating the presence of absence of tapering but low agreement when assessing for the presence of indentation and hourglass deformity. Regarding the penis stabilizer, our experience suggests that it may alter the base of the penis anatomy, but it improves capture of the organ with diminished interference from surrounding anatomy (scrotum, abdomen). Factors influencing the quality of the image were exam room set-up, patient anxiety about losing an erection, lighting, and body hair. Conclusions 3D image-based PD assessment can be implemented with minimal impact to visit efficiency. The 3D technique does not appear to reproduce complex PD measurements obtained by CADUS; however, future studies will evaluate the utility of employing this technology to a larger cohort and also to monitor treatment effect in complex PD patients. Disclosure No.

(150) Erectile Dysfunction and Peyronie’s Disease Diagnosis Rates After Penile Fracture – A Retrospective Claims Database Cohort Analysis

Abstract Introduction Penile fracture (PF) is a rare urologic emergency, with an estimated incidence of 500-600 PFs per year in the United States. Delays in surgical repair increase the risk of developing erectile dysfunction (ED) and Peyronie’s disease (PD). Objective Our objective was to analyze the rates of ED and PD following a PF using a large, multi-institutional claims database. Methods We conducted a cohort analysis utilizing the TriNetX Research database. The inclusion criteria included men ages 15 or older with a diagnosis of PF and any office visit within 5 years of the PF. Our exclusion criteria included any prior ED diagnosis, prescription of erectile aids, or penile prosthesis placement. Our primary outcome was the diagnosis of ED or prescription of erectile-aid dosing of phosphodiesterase-5 inhibitors (PDE5i) within five years. A secondary analysis was used to assess rates of PD following a PF. Subgroup analyses were performed for age and the impact of initial repair. Propensity-matching was performed to compare men with and without PF by calculating risk ratios (RR). Results 1,242 men were identified with a diagnosis of PF and subsequently matched to men without a PF, resulting in equal cohorts of 1,227 men. Men with a history of PF were more likely to receive a diagnosis of ED or require PDE5i (RR 3.18, 95% CI 2.30-4.40). Men over the age of 45 years who had a PF were more likely to develop ED or require ED treatment compared to men under 45 years (RR: 1.65, 95% CI 1.14-2.39). Men who did not undergo immediate repair had higher rates of ED diagnoses or treatment (RR: 1.84, 95% CI 1.22-2.78). Rates of PD diagnoses were significantly higher in men with a history of PF (5.8% vs 0%, p-value<0.0001). Rates of PD were significantly lower if immediate repair of the fracture was performed (RR: 0.20, 95% CI 0.10-0.41). Men over the age of 45 years with a history of a penile fracture were more likely to develop Peyronie’s Disease within 5 years compared to men under the age of 45 years with a history of penile fracture (RR: 3.73, 95% CI 1.94-7.16). Conclusions We found that a PF increases the risk of both ED and PD, especially for those treated with conservative measures or over the age of 45 years. Consequently, it is essential to follow up with these patients in the long term and survey potential adverse side effects relating to sexual function that may arise. Disclosure No.

(170) Satisfaction with Penile Prosthesis Implantation among Patients with Peyronie’s Disease Using a Contemporary Questionnaire

Abstract Introduction The Satisfaction Survey for Inflatable Penile Implants (SSIPI) is a recently validated 16-question survey used to quantitatively measure patient outcomes after penile prosthetic surgery. The survey consists of four subdomain scores representing the appearance, pain, satisfaction, and function of the penile implant. Since its validation, there have been limited studies examining its use in patients with Peyronie’s disease (PD). Objective The objective of this study is to explore the use of the SSIPI in men with Peyronie’s Disease and to determine if any factors predict patient-perceived postoperative outcomes. Methods Preoperative, intraoperative, and postoperative data for patients with PD undergoing implantation of an inflatable penile prosthesis (IPP) by a single surgeon at a tertiary care institution was retrospectively collected into a secure database. Only those patients with at least one completed SSIPI postoperatively were included in the analysis. For those patients with multiple completed SSIPI’s, only the most recently completed one was used. Linear regression and Fischer’s exact test were used to determine if there were any significant relationships between variables and the SSIPI scores. Results There were a total of 44 men with PD who underwent surgery for an IPP. 31 of them were Caucasian, 11 were African-American, and one each were Hispanic and American Indian/Native American. Median time between surgery and completion of the SSIPI at a follow-up visit was 291 days (IQR 107.75-403.50). 35 men received a Coloplast Titan and 9 received an AMS 700 CX. There was no significant difference in the overall SSIPI score and any of the subdomains between men who received different types of implants or between men of different races. All four subdomains were significantly negatively correlated with the residual curvature which was measured intraoperatively after the IPP was implanted and any adjunctive straightening techniques were used (Fig 1a-d). The appearance domain was also significantly negatively correlated with the preoperative total testosterone indicating that men with a lower total testosterone level were more satisfied with the appearance of their penis. (p < 0.05, R2 = 0.32). Interestingly, those men who underwent manual modeling (n=36) had a significantly lower score in the appearance domain (p < 0.05). Conclusions Post-operative residual curvature in men with PD undergoing implantation of an IPP is a predictor of satisfaction with the IPP. The role of preoperative testosterone and intraoperative manual modeling in how men with PD perceive the appearance of their penis postoperatively requires further investigation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific.

(119) Impact of Ethnicity on Clinical Outcomes of Intralesional CCH in Peyronie's Disease Patients Across Kaiser Permanente Southern California Database

Abstract Introduction Intralesional CCH injection is an effective treatment for Peyronie’s disease (PD) that utilizes collagenolytic enzymes to break down collagen plaque, thus reducing the penile deformity. The IMPRESS I and II clinical trials demonstrated efficacy of CCH in a predominant Caucasian population of men (95.8%). Little is known about treatment efficacy in the non-Caucasian population. Objective Using Kaiser Permanente’s ethnically diverse database, we sought to study the impact of race on CCH treatment outcomes. Methods This study examined the efficacy of intralesional CCH injection in a large healthcare system over 15 years. We defined treatment efficacy as percent change in penile curvature abnormality from baseline after a maximum of 4 treatment cycles. Impact of comorbidities on CCH efficacy was also examined. Patients with ventral curvature or initial curvature <30 ̊ or >90 ̊ were excluded from analysis. Standard statistical analysis was performed. Results 112 patients underwent CCH therapy and were included in this analysis. 46.4% of men completed all 4 cycles. Among men who received CCH, 66.1% were Caucasian, 22.3% Hispanic, and 9.8% African American. For co-morbidities, 87.5.% of men were not diabetic, while 22.3% of men had erectile dysfunction. The mean baseline pre-injection penile curvature was 51.63 degrees (range was 32-87 degrees). Caucasian men had the largest treatment response to CCH (45.6% decrease in penile curvature) compared to African American men (43.7%) and Hispanic men (40.5%), p = 0.9554. Non-diabetic men had a larger treatment response to CCH (44.9% decrease in curvature versus 39.3% in diabetics, p = 0.4726). Younger Men (age 18-44) also experienced a greater treatment response compared to other age groups (57.9% reduction in curvature, p = 0.171). There was a significant difference in number of cycles completed across different ethnicities (p = 0.0220). Hispanic men were significantly less likely to complete all 4 cycles of CCH compared to Caucasian and African American men (p=0.0004). Only 28.2% of Hispanic men completed all 4 treatment cycles. 48% of Hispanic patients report the need of language interpretation services during health appointments. Conclusions This is the largest post-market analysis of CCH treatment outcomes in a racially diverse PD population. Caucasian men had a greater treatment response after CCH injection possibly due to higher rate of completing all 4 treatment cycles. Nondiabetic men and younger men (aged 18 to 44) also had a greater treatment response after CCH injection. Hispanic men were significantly less likely to complete 4 cycles of injection therapy; possible explanations include language barriers. Future study is needed to determine if patient resources prepared in Spanish can improve treatment outcomes in Hispanic men with PD, and reduce these health care disparities observed in our study. Disclosure No.