Does climate impact inflatable penile prosthesis infection (IPP) risk? Assessment of temperature and dew point on IPP infections.

BACKGROUND: Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections. AIM: We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort. METHODS: We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken. OUTCOMES: Our primary outcome was implant infection. RESULTS: A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection. CLINICAL IMPLICATIONS: These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate. STRENGTHS AND LIMITATIONS: Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed. CONCLUSION: The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk.

Thematic analysis of the psycho-sexual symptoms in patients with Peyronie's disease present on online forums.

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea that may result in penile deformity, pain, a palpable plaque, and erectile dysfunction. In order to understand the psycho-sexual impacts of PD on patients and their partners, we selected three online forums containing the largest number of threads on PD. Threads focusing on the psycho-sexual impacts posted from January 1, 2011 to January 1, 2021 were compiled, and thematic analysis was performed on Dedoose. There were 277 unique posters, including 225 patients and 52 partners. Eighty-four categories and five themes were developed including information and social support, physical symptoms, psycho-sexual symptoms, treatment and effect, and impacts on partners and relationship. Emotional distress including depressed mood (n = 75, 33.3%) and feelings of isolation (n = 41, 18.2%) was prevalent. Partners developed sexual dysfunction including sexual dissatisfaction (n = 11, 21.2%) and dyspareunia (n = 4, 7.7%). Relationships experienced disruption (n = 14, 5.1%) or termination (n = 10, 3.6%). Posters received psychological treatment including psychotherapy (n = 20, 8.9%) and antidepressants (n = 17, 7.6%). Of these, 12 reported improvement and 11 stated no improvement. On these forums, psychological burden affecting individuals with PD and their partners is reported. Few seek help from a psychologist or therapist, and psychological distress may persist even after successful PD treatment. Further research is needed to identify strategies for effective psychological management.

AUA-recommended Antibiotic Prophylaxis for Primary Penile Implantation Results in a Higher, Not Lower, Risk for Postoperative Infection: A Multicenter Analysis.

PURPOSE: Our aim was to determine if the AUA-recommended prophylaxis (vancomycin + gentamicin alone) for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard regimens. MATERIALS AND METHODS: We performed a multicenter, retrospective study of patients undergoing primary inflatable penile prosthesis surgery. Patients were divided into those receiving vancomycin + gentamicin alone and those receiving any other regimen. A Cox proportional-hazards model was constructed adjusted for major predictors. A subgroup analysis to identify the appropriate dosage of gentamicin was also performed. RESULTS: A total of 4,161 patients underwent primary inflatable penile prosthesis placement (2,411 received vancomycin + gentamicin alone and 1,750 received other regimens). The infection rate was similar between groups, 1% vs 1.2% for standard vs nonstandard prophylaxis. In the multivariable analysis, vancomycin + gentamicin (HR: 2.7, 95% CI: 1.4 to 5.4, P = .004) and diabetes (HR: 1.9, 95% CI: 1.03 to 3.4, P = .04) were significantly associated with a higher risk of infection. Antifungals (HR: 0.08, 95% CI: 0.03 to 0.19, P < .001) were associated with lower risk of infection. There was no statistically significant difference in infection rate between weight-based gentamicin compared to 80 mg gentamicin (HR: 2.9, 95% CI: 0.83 to 10, P = .1). CONCLUSIONS: Vancomycin + gentamicin alone for antibiotic prophylaxis for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard antibiotic regimens while antifungal use is associated with lower infection risk. A critical review of the recommended antimicrobial prophylactic regimens is needed. Prospective research is needed to further elucidate best practices in inflatable penile prosthesis antimicrobial prophylaxis.

Relationships between erectile dysfunction, prostate cancer treatment type and inflatable penile prosthesis implantation.

PURPOSE: The prevalence of erectile dysfunction (ED) and the utilization of inflatable penile prosthesis (IPP) among prostate cancer patients are understudied. The aim of the study was to examine the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort. MATERIALS AND METHODS: We identified a retrospective cohort of Surveillance, Epidemiology, and End Results (SEER)-Medicare patients diagnosed with locoregional prostate cancer between 2006 and 2011 and treated with surgery or radiation. Chi-square tests were used to detect significant differences in ED rates as well as use of IPP among the subset with ED. Multivariable logistic regression was used to examine factors associated with the use of IPP. RESULTS: Among 31,233 patients in our cohort, 10,334 (33.1%) received prostatectomy and 20,899 (66.9%) received radiation. ED within 5 years was significantly more common in the prostatectomy group relative to those the radiation group (65.3% vs. 33.8%, p<0.001). In the subset of 13,812 patients with ED, the radiation group had greater median time to ED diagnosis compared to the prostatectomy group (346 vs. 133 days, p<0.001). IPP implantation was more frequent for prostatectomy patients than for radiation patients (3.6% vs. 1.4%, p<0.001). Cancer treatment type, race, and marital status were significantly associated with IPP utilization. CONCLUSIONS: ED is highly prevalent among prostate cancer patients, and IPP implantation is be underutilized. ED rates, time to ED diagnosis and utilization of IPP differed significantly by prostate cancer treatment type.

Pretreatment screening and counseling on prolonged erections for patients prescribed trazodone.

PURPOSE: We examined whether patients are appropriately screened for previous prolonged erections or priapism and counseled about trazodone complications, specifically prolonged erections and priapism, prior to trazodone treatment. MATERIALS AND METHODS: We identified patients under the age of 50 on trazodone as of February 27, 2019 at the VA New Jersey Health Care System. Patients were asked about information provided to them prior to medication initiation, occurrence of prolonged erections/priapism, and reporting rate of side effects. RESULTS: Two hundred and twenty nine out of five hundred and twenty four male patients agreed to participate in the study. Forty three out of two hundred and twenty nine of patients were informed about the side effects of prolonged erections and 37/229 of patients were informed of risk of priapism prior to treatment. Only 17/229 of patients were asked if they had had any episodes of prolonged erection or priapism in the past. Eighteen patients developed prolonged erection while taking trazodone. Only 5/18 patients who had developed prolonged erections informed their physicians. CONCLUSIONS: Only a fraction of patients were properly screened for previous prolonged erections or priapism and properly informed about the side effects of trazodone. Urologist should better educate trazodone prescribers, such as family medicine and psychiatric colleagues, regarding the side effects of trazodone. It is imperative that prescribing physicians appropriately screen and educate patients prior to trazodone initiation and instruct patients to report any treatment side effects to avoid potential long-term adverse outcomes.

Immediate preoperative blood glucose and hemoglobin a1c levels are not predictive of postoperative infections in diabetic men undergoing penile prosthesis placement.

Defining the risks associated with diabetes mellitus in patients undergoing penile prosthesis implantation remains controversial. Our study aims to assess whether preoperative hemoglobin a1c and preoperative blood glucose levels are associated with an increased risk for postoperative infection in diabetic men. We performed a retrospective review of 932 diabetic patients undergoing primary penile prosthesis implantation from 18 high-volume penile prosthesis implantation surgeons throughout the United States, Germany, Belgium, and South Korea. Preoperative hemoglobin a1c and blood glucose levels within 6 h of surgery were collected and assessed in univariate and multivariate models for correlation with postoperative infection, revision, and explantation rates. The primary outcome is postoperative infection and the secondary outcomes are postoperative revision and explantation. In all, 875 patients were included in the final analysis. There were no associations between preoperative blood glucose levels or hemoglobin a1c levels and postoperative infection rates; p = 0.220 and p = 0.598, respectively. On multivariate analysis, a history of diabetes-related complications was a significant predictor of higher revision rates (p = 0.034), but was nonsignificant for infection or explantation rates. We conclude preoperative blood glucose levels and hemoglobin a1c levels are not associated with an increased risk for postoperative infection, revision, or explantation in diabetic men undergoing penile prosthesis implantation.

A Multicenter Investigation Examining American Urological Association Recommended Antibiotic Prophylaxis vs Nonstandard Prophylaxis in Preventing Device Infections in Penile Prosthesis Surgery in Diabetic Patients.

PURPOSE: American Urological Association (AUA) antibiotic prophylaxis recommendations may be insufficient for covering organisms commonly found in penile prosthesis infections. In this study we assess the difference between AUA recommended antibiotic prophylaxis and nonstandard prophylaxis in preventing device infections in penile prosthesis surgery performed in diabetic patients. MATERIALS AND METHODS: A multicenter, retrospective cohort study of diabetic patients undergoing primary penile prosthesis surgery was performed between April 2003 and August 2018. Eighteen institutions from the United States, Europe and Korea contributed. The association between antibiotic prophylaxis type and postoperative penile prosthesis infections, device explantations and revision surgeries was assessed. RESULTS: Standard AUA antibiotic prophylaxis was followed in 48.6% (391) of cases while nonstandard prophylaxis was used in 51.4% (413). Common nonstandard antibiotic prophylaxis included vancomycin-gentamycin-fluoroquinolone, clindamycin-fluoroquinolone, and vancomycin-fluoroquinolone among other combinations. Patients who received AUA prophylaxis had significantly more postoperative device infections (5.6% vs 1.9%, p <0.01) and explantations (8.3% vs 2.0%, p <0.001) compared to those who received nonstandard prophylaxis. Patients who received AUA prophylaxis had significantly higher odds of a postoperative device infection (OR 2.8, 95% CI 1.1-7.3) and explantation (OR 3.6, 95% CI 1.4-9.1) compared to those who received nonstandard prophylaxis. CONCLUSIONS: Diabetic men with erectile dysfunction who received standard AUA prophylaxis for penile prosthesis surgery had significantly greater odds of experiencing a postoperative device infection and device explantation compared to patients who received nonstandard prophylaxis. Our study provides a strong rationale for a prospective investigation to establish the most appropriate prophylaxis strategy in penile prosthesis surgery.

Etiology of Erectile Dysfunction and Duration of Symptoms in Patients Undergoing Penile Prosthesis: A Systematic Review.

INTRODUCTION: Inadequate treatment of men with erectile dysfunction (ED) subjects them and their partners to lost quality of life, yet little is known about the cause and duration of symptoms that lead to penile prosthesis (PP) placement. AIM: We performed a systematic review addressing cause and duration of symptoms before implantation. METHODS: We searched PubMed, Embase, and Cochrane for articles published between January 1, 1965-July 20, 2016, reporting on PP for ED. Studies were assessed for quality. Body of evidence strength was categorized in accordance to American Urological Association (AUA) categorization: grade A (well-conducted, highly-generalizable randomized controlled trials (RCTs) or exceptionally strong observational studies with consistent findings), grade B (RCTs with some weaknesses of procedure/generalizability or moderately strong observational studies with consistent findings), or grade C (RCTs with serious deficiencies of procedure/generalizability, have small sample sizes, or other problems that potentially confound interpretation). This review was performed as part of the 2018 AUA ED Clinical Guidelines, with the support of the AUA. MAIN OUTCOME MEASURES: Cause and duration of symptoms before PP were assessed. RESULTS: We reviewed 113 articles constituting 150 study arms. All studies were observational (body of evidence strength grade C). Of these arms, only 19 reported on ED duration. Mean duration was 56 months for men undergoing inflatable penile prosthesis (IPP) placement (38.7 months for those after prostatectomy) and 72 months for those undergoing malleable penile prosthesis placement. Diabetic patients undergoing IPP had mean ED duration of 75 months. Among arms reporting on IPPs, causes of ED were vascular disease (47 arms; range 2.9-62.0%; mean 31.9%), diabetes (61 arms; range 12.8-77.8%; mean 28.3%), and pelvic surgery or trauma (49 arms; range 0.5-49.7%; mean 20.3%). CONCLUSION: Nearly all men undergoing PP have ED of organic causes, whereas diabetic patients and patients receiving malleable penile prosthesis have the longest ED duration. Factors driving this relative delay require additional investigation. Post-prostatectomy IPP placement is offered relatively late, on average. Bajic P, Mahon J, Faraday M, et al. Etiology of Erectile Dysfunction and Duration of Symptoms in Patients Undergoing Penile Prosthesis: A Systematic Review. Sex Med Rev 2020;8:333-337.

Impact of serious mental illness on the treatment and mortality of older patients with locoregional high-grade (nonmetastatic) prostate cancer: retrospective cohort analysis of 49 985 SEER-Medicare patients diagnosed between 2006 and 2013.

BACKGROUND: The influence of serious mental illness (SMI) on the treatment and survival of patients with high-grade prostate cancer is not well understood. We compared the initial cancer treatment and cancer-specific mortality of SEER-Medicare patients with locoregional high-grade (nonmetastatic) prostate cancer with and without preexisting SMI. METHODS: We identified SEER-Medicare patients who were 67 years of age or older diagnosed between 2006 and 2013 with locoregional high-grade (nonmetastatic) prostate cancer. Preexisting SMI was identified by claims indicative of bipolar disorder, schizophrenia, and other psychotic disorder, during the 2 years before cancer diagnosis. We used multivariable binary logistic regression to examine associations between SMI and receipt of surgery or radiation concurrent with hormone therapy (definitive initial treatment) within 1 year after cancer diagnosis. We used Kaplan-Meier survival curves, as well as Cox proportional hazards and competing risk models to evaluate unadjusted and adjusted associations between SMI and 5-year cancer-specific survival. RESULTS: Among 49 985 patients with locoregional high-grade (nonmetastatic) prostate cancer, 523 (1.1%) had SMI and 49 462 (98.9%) had no SMI. Overall, SMI was associated with reduced odds of receiving surgery (OR = 0.66, 95% CI: 0.49-0.89) or radiation concurrent with hormone therapy (OR = 0.81, 95% CI: 0.67-0.98) as initial treatments in the year after cancer diagnosis. Additionally, SMI was associated with higher hazard of 5-year cancer-specific death (HR = 1.41, 95% CI: 1.06-1.89) after accounting for competing risks of non-cancer death. CONCLUSION: Among SEER-Medicare patients with locoregional high-grade (nonmetastatic) prostate cancer, those with preexisting SMI-relative to those without these conditions-were less likely to receive definitive initial treatment in the year after diagnosis and had poorer cancer-specific survival 5 years after diagnosis.

Penile Prosthesis Reservoir Removal: Surgical Description and Patient Outcomes.

BACKGROUND: Removal of the penile prosthesis reservoir can be technically challenging because of its difficult locations either deep in the pelvis or high in the abdominal wall. AIM: To describe a detailed surgical technique for reservoir removal through a penoscrotal approach. METHODS: We describe our preferred method for removal of prosthetic reservoir and present a retrospective review of patient outcomes after reservoir removal. MAIN OUTCOME MEASURE: Primary outcomes included immediate or late complications. Secondary outcomes included operative time. RESULTS: 34 patients underwent reservoir removal with the use of our described technique. 23 patients (67.6%) had reservoirs removed because of device malfunction and 11 (32.4%) because of infection. A total of 18 reservoirs (52.9%) were found in the space of Retzius (SOR), whereas the other 16 (47.1%) were in an alternative/ectopic space. 2 cases (5.9%) required a counterincision to remove the reservoir. Mean overall operative time was 96.2 minutes (range 35-175). There were no complications in this series. There was no statistical difference in operative time between reservoirs removed because of malfunction when compared with infection (P = .283). However, there was a difference in operative time between reservoirs removed from the SOR when compared with those removed from an ectopic space, with mean operating room times of 104.5 and 75.4 minutes, respectively (P = .001). CLINICAL IMPLICATIONS: Reservoir removal through a penoscrotal incision is feasible and safe. STRENGTH & LIMITATIONS: This is the first report, to our knowledge, describing surgical techniques and outcomes for reservoir removal. Limitations include its retrospective nature and lack of validated questionnaires to assess patient satisfaction. CONCLUSION: Although removal of a reservoir deep in the SOR or placed in alternate/ectopic locations can be challenging, the use of a lighted retractor, meticulous dissection, and a few technical maneuvers described allow for safe removal of the reservoir completely intact while avoiding complications. Our technique for a secondary incision in particularly difficult cases is also described. Clavell-Hernández J, Aly SG, Wang R, et al. Penile Prosthesis Reservoir Removal: Surgical Description and Patient Outcomes. J Sex Med 2019;16:146-152.

Xiaflex for Treatment of Peyronie's Disease.

Xiaflex or collagenase Clostridium histolyticum intralesional injections are safe and effective as first-line treatment for Peyronie's disease.

Corrigendum: Incorrect Spelling of Author's Name: US Preventive Services Task Force prostate-specific antigen screening guidelines result in higher Gleason score diagnoses.

[This corrects the article on p. 423 in vol. 58.].

US Preventive Services Task Force prostate-specific antigen screening guidelines result in higher Gleason score diagnoses.

Purpose: To evaluate the impact that the 2012 US Preventive Services Task Force (USPSTF) prostate-specific antigen (PSA) screening guidelines have had on the diagnosis of prostate cancer, we compared the incidence and distribution of new cases diagnosed in 2011-before the USPSTF PSA screening recommendations versus 2014 at which time the guidelines were widely adopted. Materials and Methods: We identified all prostate biopsies performed by a large urology group practice utilizing a centralized pathology lab. We examined total biopsies performed, percentage of positive biopsies, and for those with positive biopsies examined for differences in patient age, PSA, and Gleason score. Results: A total of 4,178 biopsies were identified - 2,513 in 2011 and 1,665 in 2014. The percentage of positive biopsies was 27% in 2011 versus 34% in 2014 (p<0.0001). Among patients with positive biopsies, we found statistically significant differences between the 2 cohorts in the median ages and Gleason scores. Patients were about 1 year younger in 2014 compared to 2011 (t-test; p=0.043). High Gleason scores (8-10) were diagnosed in 19% of the 2014 positive biopsies versus 9% in the 2011 positive biopsies (chi square; p<0.0001). Conclusions: After the widespread implementation of the 2011 USPTF PSA screening guidelines, 34% fewer biopsies were performed with a 29% increase in positive biopsy rates. We found a significantly higher incidence of high grade disease in 2014 compared with 2011. The percentage of patients with positive biopsies having Gleason scores 8-10 more than doubled in 2014. The higher incidence of these more aggressive cancers must be part of the discussion regarding PSA screening.

Isolated Non-ascitic Peritoneal Carcinomatosis from Metastatic Prostate Cancer.

Prostate cancer most commonly metastasizes to bone, lung and liver. Omental metastasis of prostate cancer is extremely rare, with only a few cases reported in the literature, many of which have associated ascites. We present a case of non-ascitic omental metastasis of prostate cancer without any bone metastases. Furthermore, this patient has had two negative measurements of circulating tumor cells (CTCs) in the blood, suggesting a non-hematogenous route of metastasis to the omentum.

Male Sexual Function and Smoking.

INTRODUCTION: Erectile dysfunction (ED) is a common disorder that has many potential etiologies, including hormonal imbalances, psychogenic factors, neurologic disorders, vascular insufficiency, and other risk factors. Cigarette smoking has been well established as a risk factor for cardiovascular disease and stroke, but the relation between smoking and ED is less frequently considered. AIM: To review the current literature that analyzes the association between cigarette smoking and ED. METHODS: The PubMed database was searched using the terms erectile dysfunction and smoking and erectile dysfunction and tobacco through December 2015. MAIN OUTCOME MEASURES: Main outcome measures were significant changes in erectile function in relation to smoking status. RESULTS: Eighty-three studies and articles were reviewed. Multiple human studies, animal studies, case series, cross-sectional, and cohort studies analyzed the relation between smoking or nicotine and ED. CONCLUSION: There is substantial evidence showing that cigarette smoking is a risk factor for ED. Multiple human, animal, case series, cross-sectional, and cohort studies support this conclusion. A positive dose-response relation also is suggested such that increased quantity and duration of smoking correlate with a higher risk of ED. Smoking cessation can lead to recovery of erectile function, but only if limited lifetime smoking exposure exists. Smoking contributes to ED in different ways, especially by causing penile vasospasm and increased sympathetic nervous system tone.

Evidence-Based Management Guidelines on Peyronie's Disease.

INTRODUCTION: Despite recent advances in our knowledge and treatment strategies in Peyronie's Disease (PD), much remained unknown about this disease. AIM: To provide a clinical framework and key guideline statements to assist clinicians in an evidence-based management of PD. METHODS: A systematic literature search was conducted to identify published literature relevant to PD. The search included all relevant articles published up to June 2015, including preclinical studies and published guidelines. References used in the text were assessed according to their level of evidence, and guideline recommendations were graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Owing to the paucity of larger series and randomized placebo-controlled trials with regard to surgical intervention, guideline statements are provided as clinical principle or expert opinion. MAIN OUTCOME MEASURES: This literature was discussed at a panel meeting, and selected articles with the highest evidence available were used to create consensus guideline statements for the Fourth International Consultation on Sexual Medicine guidelines on PD. RESULTS: In addition to existing Third International Consultation on Sexual Medicine guidelines on PD, seven new summary recommendations were created. CONCLUSION: A greater understanding of the scientific basis of PD is greatly needed to address our understanding of the pathophysiology, clinical epidemiology, psychosocial, and diagnostic assessment as well as treatment strategies.

The Evolution of the Inflatable Penile Prosthesis Reservoir and Surgical Placement.

The traditional inflatable penile prosthesis (IPP) reservoir placement is below the transversalis fascia in the space of Retzius. In 2002, Dr. Steve Wilson described ectopic reservoir placement, thereby providing a safe and effective alternative for implant surgeons. This new approach obviated the need for a second incision and decreased operative times during surgery. In the manuscript, he also described the introduction of a reservoir lock-out valve, which prevents autoinflation of the penile implant. The development of lockout valves and flat reservoirs has contributed to the early success and feasibility of submuscular placement techniques. Thirteen years after Dr. Wilson's pivotal study, this technique should be in the armamentarium of all urologic prosthetic surgeons. Accordingly, in certain subsets of patients, ectopic/ submuscular reservoir site placement should be considered a safe, effective alternative to standard reservoir placement in the space of Retzius.

Peyronie's Disease: AUA Guideline.

PURPOSE: The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of Peyronie's disease. MATERIALS AND METHODS: A systematic review of the literature using the PubMed®, EMBASE® and Cochrane databases (search dates 1/1/1965 to 1/26/15) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of PD. The review yielded an evidence base of 303 articles after application of inclusion/exclusion criteria. RESULTS: The systematic review was used to create guideline statements regarding treatment of PD. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high quality evidence; high certainty), B (moderate quality evidence; moderate certainty), or C (low quality evidence; low certainty). Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional consensus statements related to the diagnosis of PD are provided as Clinical Principles and Expert Opinions due to insufficient published evidence. CONCLUSIONS: There is a continually expanding literature on PD; the Panel notes that this document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient's history, values, and goals for treatment. As the science relevant to PD evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care.

Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD).

OBJECTIVE: To examine the safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD), using a pooled safety analysis of patients who received at least one dose of CCH in any of six clinical studies. PATIENTS AND METHODS: Patients from six clinical studies, including three randomised, double-blind, placebo-controlled studies and three open-label safety and efficacy studies, were included if they had received at least one dose of 0.58 mg CCH. Adverse events (AEs), including treatment-emergent AEs, treatment-related AEs, and serious AEs (SAEs), were characterised. Potential immunogenicity-related AEs were evaluated through examination of increased anti-AUX-I and anti-AUX-II antibody levels, AEs, and reported terms possibly associated with immunological or hypersensitivity events. RESULTS: Overall, 85.8% of 1 044 pooled patients reported at least one treatment-related AE. The most frequently reported (≥25.0% of patients) treatment-related AEs included penile haematoma (82.7% had the verbatim 'penile bruising'), penile pain, and penile swelling. Most patients (75.2%) had mild- or moderate-severity treatment-related AEs, and 14.2% had no treatment-related AEs. Nine patients (0.9%) had treatment-related SAEs: five with penile haematoma and four with corporal rupture. There was no association between AEs and anti-AUX-I or anti-AUX-II antibody levels across treatment cycles, and no systemic hypersensitivity reactions occurred. CONCLUSIONS: This pooled safety analysis shows that although non-serious and serious treatment-related AEs can occur after CCH treatment for PD, most were non-serious and the SAEs were manageable. Providers should be prepared to manage possible SAEs.