Predictors of hinge effect in patients with Peyronie's disease.

BACKGROUND: Patients with Peyronie's disease present with a variety of penile deformities. Those with hinge effect can experience bothersome buckling of the erection and instability during penetrative sex; however, the actual characteristics and clinical implications are not fully understood. AIM: To determine the factors that cause hinge effect and to assess the role on surgical intervention. METHODS: This retrospective review included 1223 consecutive patients who were examined by a single surgeon and had a complete penile duplex evaluation with curvature and hinge assessment. Baseline demographics, penile duplex findings, and clinical outcomes were used to assess for predictors of hinge effect. OUTCOMES: Analyses were performed to assess preoperative predictors of hinge effect and surgical intervention. RESULTS: Hinge effect was observed at the time of penile duplex Doppler examination in 33% of patients. Circumferential girth discrepancy at point of indentation (odds ratio [OR] 1.82; P < .001), rigidity of erection (OR, 0.82; P = .002), and degree of primary curvature (OR, 1.03; P < .001) predicted the presence of hinge effect. When controlling for rigidity, a girth discrepancy >1 cm did appear to be associated with a hinge. CLINICAL IMPLICATIONS: Circumferential girth discrepancy >1 cm, regardless of erectile rigidity, can be associated with hinge effect. STRENGTHS AND LIMITATIONS: As a strength, this study included the largest cohort of patients with Peyronie's disease, all of whom were examined in a rigorous and uniform manner via the same operative counseling. However, the study is limited by its retrospective nature and potential for selection and observer bias, given that the treating physician was also assessing all penile deformities as well as performing operative intervention. CONCLUSIONS: The presence of hinge effect can cause instability of erections during penetrative sex. Multiple factors may predispose patients to a hinge effect, including the quality of erection and severity of curvature. But when controlling for rigidity, a girth discrepancy >1 cm did appear to be associated with a hinge. While many factors, such as baseline erectile dysfunction and severity of curvature, are important in determining the optimal surgical intervention, assessing for preoperative hinge effect also influenced the surgical approach.

Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy.

INTRODUCTION: The initial clinical trials for intralesional collagenase Clostridium histolyticum (CCh) injection therapy for Peyronie disease (PD) excluded men on antiplatelet or anticoagulant medications except those on low-dose aspirin. Men with PD who take such medications present a challenging clinical scenario because of a lack of evidence regarding the safety of CCh while on these drugs. AIM: To evaluate safety outcomes among patients continuing anticoagulant and antiplatelet therapy during ongoing intralesional CCh injection treatment for PD. METHODS: An institutional review board approved a database of 187 patients treated with CCh at an academic men's health practice from January 2016 through April 2019 was reviewed. Men on antiplatelet/anticoagulant medications were not instructed to stop these agents. Data on patient demographics, comorbidities, CCh injection details, use or nonuse of antiplatelet/anticoagulant medications, and adverse events were extracted from the electronic medical record. Rates of hematoma formation, bruising, swelling, and corporal rupture were determined. Univariate statistical analysis compared clinical data and adverse events between men on or off antiplatelet/anticoagulant medications. MAIN OUTCOME MEASURE: Statistical comparison of adverse events in those taking or not taking antiplatelet or anticoagulant medications while undergoing intralesional CCh injection therapy for PD. RESULTS: Of 187 men undergoing CCh treatment, 33 (17.6%) were on concomitant antiplatelet or anticoagulant therapy. Aspirin 81 mg alone was the most common pharmacologic agent (58% of men on antiplatelet/anticoagulants); medications also included other antiplatelet drugs, warfarin, and novel oral anticoagulants (NOACs). Men taking blood thinners during intralesional CCh injection therapy experienced no statistical difference in rates of bruising, swelling, or hematoma formation compared with men not on antiplatelet/anticoagulants. No corporal ruptures were observed in either group. Men on antiplatelet or anticoagulant therapy were more likely to be older (64 vs 58 years old, P = 0.005), have hypertension (P = 0.025), and have hyperlipidemia (0.009). CLINICAL IMPLICATIONS: Intralesional CCh injection therapy may be offered to men on antiplatelet/anticoagulant medications without increased risk of adverse events. STRENGTH & LIMITATIONS: This study evaluated the experience of a single surgeon, with a systematic evaluation of adverse events captured in a robust electronic medical record. The retrospective nature of this study limits conclusions but builds upon work performed in the initial clinical trials for CCh. CONCLUSION: Our findings suggest that antiplatelet and anticoagulant medications do not increase the risk of adverse events during intralesional CCh injection therapy for PD. Amighi A, Regets KV, Nork JJ, et al. Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy. J Sex Med 2020;17:353-356.

Peyronie's Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes.

INTRODUCTION: Peyronie's disease (PD) is characterized by pain, deformity, sexual dysfunction, and psychological bother. Several treatments are available with varying levels of efficacy, and significant limitations exist with the currently available literature. AIM: To explore modern-era methodological challenges inherent to PD research as they pertain to intervention studies. METHODS: We performed a critical review of the PD intervention literature to identify common methodological challenges with emphasis on aspects of patient assessment and treatment outcomes, study design, and statistical analysis. The key objective was to provide an impetus on which to build future research protocols, rather than focus on weaknesses with any individual studies. MAIN OUTCOME MEASURE: Expert opinion was used to summarize limitations with commonly reported objective outcomes such as penile curvature, girth, and length along with imaging modalities and objective questionnaires. Appropriate study design and statistical analysis were also reviewed to discuss common pitfalls in the PD literature. RESULTS: There are multiple shortcomings inherent to studying objective PD outcomes such as penile curvature, girth, and length. These include lack of standardized protocols for preintervention and postintervention assessment, interobserver and intraobserver variability, and lack of consistent definitions for what defines an objective outcome as clinically "meaningful" for patients. Similarly, imaging studies including penile ultrasound are subject to marked variation, thereby limiting their utility to measure predefined primary or secondary study outcomes including cavernosal artery hemodynamics and penile plaque size. Objective and validated questionnaires such as the Peyronie's Disease Questionnaire and International Index of Erectile Function require that patients have recently engaged in sexual activity, which is challenging for many patients as a result of penile deformity with PD. Finally, careful study design and statistical analysis (including appropriate study power) are imperative to ensure reliable results. Current shortcomings in the majority of studies contribute to the low level of evidence available for most PD interventions. CLINICAL IMPLICATIONS: Future PD intervention studies should focus on optimizing study design and statistical analysis. Furthermore, authors must incorporate standardized protocols for assessing preintervention and postintervention outcomes. STRENGTH & LIMITATIONS: The current analysis and recommendations for future study are based on the expertise and opinion of the manuscript authors. CONCLUSION: Multiple areas of weakness in study design, statistical analysis, and patient outcomes assessment limit the reliability of data derived from PD intervention studies in the modern era. The global themes identified herein should serve as a basis upon which to build future research protocols. Ziegelmann MJ, Trost LW, Russo GI, et al. Peyronie's Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes. J Sex Med 2020;17:364-377.

Impact of the Advent of Collagenase Clostridium Histolyticum on the Surgical Management of Peyronie's Disease: A Population-Based Analysis.

INTRODUCTION: Penile plication or partial excision with grafting has traditionally been the first-line treatment for stable Peyronie's disease (PD). Numerous injection therapies (ITs) have been introduced over the last few decades. Intralesional collagenase clostridium histolyticum (CCH) was U.S. Food and Drug Administration approved in 2013 for patients with stable disease, curvature ≥30° and ≤90°, and intact erectile function. The impact of the advent of CCH on the surgical management of PD is unknown. AIM: We studied the effect of IT on the surgical management of PD in a population-based analysis. METHODS: The Statewide Planning and Research Cooperative System database, which provides statewide level of all-payer data on patients in the outpatient, inpatient, ambulatory, and emergency department setting in New York State was reviewed. Patients undergoing a penile prosthesis for concurrent erectile dysfunction were excluded. MAIN OUTCOME MEASURE: Descriptive statistics and multivariable logistic regression modeling were used to assess factors influencing choice of injection therapy vs surgical therapy (penile plication or partial excision with grafting). RESULTS: From 2003-2016, 547 patients with PD presented for management. Median age was 56 years and 57% were white. Over the study period, surgical management was used less often as the primary procedure with a concurrent increase in use of IT (P < .001). On multivariable modeling, patients more likely to receive IT as treatment for penile curvature were younger (odds ratio [OR]: 1.26; P = .002; CI: 1.09-1.46), of higher socioeconomic status (OR: 1.14; P = .037; CI: 1.01-1.29), presented in the post-CCH era (OR: 1.17; P = .018; CI: 1.03-1.33) and presented to a surgeon with a high volume practice (OR: 1.25; P = .007; CI: 1.07-1.48). Patients presenting in the post-CCH era were 17% significantly more likely to receive IT. CLINICAL IMPLICATIONS: ITs like CCH are increasingly displacing surgical management as the primary treatment option of Peyronie's disease. STRENGTHS & LIMITATIONS: The Statewide Planning and Research Cooperative System database is particularly useful for this analysis because it is an all-payer database that tracks patients longitudinally across various health care settings-outpatient and inpatient. LIMITATIONS: It only includes patients in New York State limiting generalizability. The retrospective nature of the analysis makes it subject to the biases inherent in such reports. Specific disease level characteristics (eg, degree of curvature, duration of disease, and associated deformities) were not available. CONCLUSION: Since the introduction of CCH, there has been a markedly decreasing trend in the utilization of surgery as the primary modality in the management of PD-associated penile curvature. Sukumar S, Pijush DB, Brandes S. Impact of the Advent of Collagenase Clostridium Histolyticum on the Surgical Management of Peyronie's Disease: A Population-Based Analysis. J Sex Med 2020;17:111-116.

A modified technique for intralesional injection of collagenase Clostridium histolyticum for Peyronie's disease results in reduced procedural morbidity using a standardized hematoma classification rubric.

PURPOSE: Early clinical trials of injectable collagenase Clostridium histolyticum (CCh) for Peyronie's disease (PD) demonstrated safety and efficacy. Since then, modified injection protocols have been proposed. Adverse events-such as bruising, swelling, hematoma, and corporal rupture-exceed 50% in many studies, but lack of standardization of hematoma severity limits conclusions about the relative safety of protocols. We propose a modification of the standard injection technique that aims to decrease the rates of adverse events. We further describe a hematoma classification rubric that may standardize safety assessment. METHODS: A modified injection procedure, termed the "fan" technique, was employed in the treatment of PD. All men receiving CCh from January 2016 through January 2019 at a single institution were included in an institutional review board (IRB) approved database. Treatment outcomes and adverse events were retrospectively assessed. A three-tiered hematoma classification rubric was devised to standardize reporting of hematoma, which was defined as concurrent bruising and swelling at the site of injection without loss of erection. RESULTS: Using the fan technique, 152 patients received 1323 injections. Eight hematomas (5.3% of all patients, 0.6% of all injections) were observed. The number of grade I, grade II, and grade III hematomas were 3, 2, and 3, respectively. Bruising or swelling not meeting the definition of hematoma was seen in 54.6% and 27.0% of patients, respectively. There were zero corporal ruptures. CONCLUSION: A modified injection technique results in reduced procedural morbidity. A hematoma classification system provides clarity and standardization to the assessment of safety in PD treatment. Further clinical studies with control arms are required to verify these findings.

Evolution of the surgical sealing patch TachoSil® in Peyronie's disease reconstructive surgery: technique and contemporary literature review.

PURPOSE: The aim of this study is to review the current literature that reports outcomes of Peyronie's disease (PD) reconstructive surgery using the collagen fleece TachoSil® (Baxter, CA, USA), a novel graft that has self-adhesive properties and gained popularity in recent years. METHODS: A literature review was performed through PubMed between 2013 and 2018 regarding the use of TachoSil® in PD penile reconstructive surgery. Keywords used for the search were: Peyronie's disease, surgical therapy, surgical outcomes, grafting techniques, graft materials, collagen fleece, surgical patch, and TachoSil. RESULTS: Grafting procedures are indicated for men with PD and preserved erectile function. TachoSil® is a novel graft used for defect closure after tunical incision or partial plaque excision. Long-term results of this technique are encouraging and reliable. One major advantage over other grafts is that the TachoSil® does not require suture fixation leading to significantly decreased operative times. Another indication is residual curvature correction by plaque incision and grafting/sealing with TachoSil® during penile prosthesis implantation in patients with PD and severe erectile dysfunction. Besides reduced operative times, the major advantage is that there is no risk of device puncture because of the self-adhesive properties of the TachoSil®. CONCLUSIONS: The TachoSil® has emerged as a safe, reliable, and promising graft in PD reconstructive surgery. Until now, this graft has met the expectations as a durable and effective graft, not only for grafting techniques but also for residual curvature correction during penile prosthesis implantation. However, future research is encouraged, preferably within prospective multicenter studies.

A universal mathematical model applied to the congenital ventral penile curvature.

INTRODUCTION: The macroscopic dynamic of fetal penis development presents a pattern resembling the unfolding of a spiral, so congenital ventral penile curvature could indicate that this natural sequence has been interrupted. Our aim in this article is to offer a mathematical model of congenital ventral curvature of the penis. MATERIALS AND METHODS: Five individuals who presented with congenital ventral penile curvature and three who presented with acquired penile ventral curvature due to Peyronie's disease were evaluated. The penises were photographed during an induced erection test and the penile curvature patterns were compared with an equiangular spiral. When an association was found, a potential relationship to the golden spiral-a type of equiangular spiral-was also assessed. The mathematical spiral relationships were analyzed using Wolfram CDF Player® (Logarithmic Spiral) and PhiMatrix® software. The Wolfram software generated logarithmic spirals equivalent to the penile curvature with appropriate mathematical values. The PhiMatrix software, which builds any golden spirals from golden rectangles, was used to check whether the spiral was golden as well as equiangular. RESULTS: An equiangular spiral that was also golden was found in all cases of congenital ventral penile curvature. In contrast, none of the acquired penile ventral curvature cases showed a specific pattern. CONCLUSION: Congenital ventral penile curvature has the mathematical pattern of a golden spiral. Our results offer a mathematical algorithm for potential use in surgical reconstruction procedures, regenerative medicine, tissue engineering, robotics, and body-machine interfaces.

[Peyronie's Disease: update in 2020]. / Maladie de Lapeyronie†: le point en 2020.

Peyronie's disease (PD) is a relatively unknown cause of sexual dysfunction. Symptoms may include the appearance of an erectile deformity, pain in the penis and erectile dysfunction (ED). The etiology is most often unclear, and medical treatments are limited, although improvement is always possible. However, surgical treatment remains the only option when the disease has stabilized and in the event of significant erectile and sexual disability.

La maladie de Lapeyronie (MDL) est une cause relativement méconnue de dysfonction sexuelle. La symptomatologie peut associer l'apparition d'une déformation en érection, des douleurs de la verge et une dysfonction érectile (DE). L'étiologie est le plus souvent floue, et les traitements médicaux limités, même si une amélioration est toujours possible. Le traitement chirurgical reste cependant la seule solution lorsque la maladie est stabilisée et en cas de handicap érectile et sexuel important.

Outcomes of a Novel Penile Traction Device in Men with Peyronie's Disease: A Randomized, Single-Blind, Controlled Trial.

PURPOSE: Current penile traction therapy devices have significant limitations, including the need to use them for 3 to 8 hours per day. Given these issues, the novel RestoreX® penile traction therapy device was developed in cooperation with Mayo Clinic. MATERIALS AND METHODS: We performed a randomized, controlled, single-blind, intent to treat trial (ClinicalTrials.gov NCT03389854) in men with Peyronie's disease who were assigned to the penile traction therapy device for 30 to 90 minutes per day or to no therapy for 3 months. Study inclusion criteria were curvature 30 degrees or greater with no study exclusions due to complex curvature, hourglass deformity, prior Peyronie's disease therapy or surgery, or calcification. The primary outcome was safety and secondary outcomes were penile length and curvature, and questionnaire responses. RESULTS: A total of 110 men were randomized 3:1 to the penile traction therapy group or the control group. The cohorts were well matched with a mean age of 58.4 years, a 49.7-month Peyronie's disease history and 59.3 degree curvature. Overall penile traction therapy was well tolerated with only transient and mild adverse events reported. At 3 months men undergoing penile traction therapy demonstrated significant improvements over controls in penile length (1.5 vs 0 cm, p <0.001), curvature (-11.7 vs 1.3 degrees, p <0.01) and erectile function (4.3 vs -0.7, p = 0.01) according to the International Index of Erectile Function-Erectile Function among men with erectile dysfunction. Overall 77% of the men on penile traction therapy experienced improved curvature (mean -17.2 degrees in 28.2% of responders) while 94% achieved increased length (1.6 cm in 10.9%). Counter bending and the white line indicator improved efficacy, validating key device innovations. Of men who had previously used other penile traction therapy devices 100% preferred the RestoreX device. CONCLUSIONS: Penile traction therapy with the RestoreX device for 30 to 90 minutes per day was safe, and resulted in significant and clinically meaningful improvements in penile curvature and length in men with Peyronie's disease, and in erectile function in men with erectile dysfunction and Peyronie's disease with no significant adverse events. To our knowledge these data represent the only reported improvements for any device used less than 3 to 8 hours per day.

What role do pharmaceuticals play in the treatment of Peyronie's disease and is there a need for new emerging drugs?

INTRODUCTION: Finding novel medical treatment for Peyronie's disease (PD) has suffered from similar limitations and difficulties as other fibrotic diseases.Areas covered: Underlying fibrosis, there is a vastly complex intertwining of several pathways. Focusing on a single target during antifibrotic drug development has not led to the development of many efficacious drugs, especially in PD. Inhibiting one cog in this large machinery usually leads to activation of compensatory mechanisms.Expert opinion: Novel strategies in drug discovery such as phenotypical drug screening and gene expression profiling technologies could provide a solution for this impasse.

Optimizing collagenase Clostridium histolyticum therapy for Peyronie's disease using a novel approach with percutaneous needle tunnelling.

OBJECTIVES: To compare the efficacy and safety of a combined treatment of percutaneous needle tunnelling (PNT) and a modified collagenase Clostridium histolyticum (CCH) protocol (PNT/CCH) vs the modified protocol alone (CCH) in the treatment of Peyronie's disease (PD). PATIENTS AND METHODS: A prospective registry of patients treated with a modified CCH protocol was maintained between June 2014 and February 2018. The last 50 patients received PNT as an adjuvant therapy (PNT/CCH), and their data were compared with those of the other 94 patients treated previously (CCH). PNT involves the creation of multiple holes made percutaneously in the plaque before each injection. The modified protocol consisted of two collagenase injections, at 1-week intervals, followed by penile modelling. Patients used penile traction therapy, tadalafil and pentoxifylline for the next 2 months and were followed up for 6 months. The main outcome was improvement of curvature. Secondary outcomes were improvements in erectile function, PD symptoms, stretched penile length and satisfaction. RESULTS: Improvement in curvature was greater in patients in the PNT/CCH group than in the CCH group (mean ± sd 19.2 ± 6.1° vs 12.7 ± 5.0°; P < 0.001 [36.2 ± 12.5% vs 28.1 ± 14.5%; P = 0.001]). Compared with baseline, both interventions were associated with significant improvement in secondary outcomes. The main complications were ecchymosis, bruising and penile pain, with no significant differences between groups. CONCLUSIONS: Treatment of PD with CCH using our modified protocol in combination with PNT is safe and more effective than the modified protocol alone, with the potential for improved cost-effectiveness.

Penile traction therapy with the new device 'Penimaster PRO' is effective and safe in the stable phase of Peyronie's disease: a controlled multicentre study.

OBJECTIVES: To evaluate the efficacy and safety of a new penile traction device (PTD), 'Penimaster PRO', in a group of patients with stable Peyronie's disease (PD) compared with a non-intervention group in a multicentre study. MATERIAL AND METHODS: A total of 93 patients with chronic stable PD (without erectile dysfunction, with no significant pain, and with a unidirectional curvature of at least 45° being stable for > 3 months) were recruited and followed for a 12-week period. Of these patients, 47 were randomly assigned to the Penimaster PRO group (PG) and 46 to the non-intervention group (NIG). Patients were asked to apply the PTD 3-8 h a day for 12 consecutive weeks, with specific instructions regarding the progressive increase of traction force applied to the penis over time. The primary outcome of the study was the change in the degree of curvature measured in the fully erect state after intracavernosal injection of alprostadil at baseline, 1, 2 and 3 months. Other variables, such as the type of curvature, stretched penile length (SPL), Peyronie's Disease Questionnaire (PDQ) scores, erectile function domain of the International Index of Erectile function (IIEF-EF) score and adverse events (AEs) were also assessed in each visit. RESULTS: Forty-one patients in the PG and 39 in the NIG completed the study. There was an overall reduction in curvature of 31.2° (P < 0.001) at 12 weeks compared to baseline in the PG, representing a 41.1% improvement from baseline, which significantly correlated with the number of daily hours the device was applied in a dose-dependent manner. Those patients using the device < 4 h/day experienced a reduction of 15°-25° (mean 19.7°, 28.8% improvement; P < 0.05), while patients using the device > 6 h/day experienced greater curvature reduction, ranging from 20° to 50° (mean of 38.4°, 51.4% improvement; P < 0.001). In contrast, no significant changes in curvature were observed in the NIG. Furthermore, SPL increased significantly in the PG compared to baseline and compared with the NIG, ranging from 0.5 to 3.0 cm (mean 1.8 cm; P < 0.05). The IIEF-EF score also improved in patients in the PG (by a mean of 5 points). Mild AEs occurred in 43% of patients, such as local discomfort and glans numbness. CONCLUSION: The use of the Penimaster PRO PTD, a non-invasive treatment, should be offered to patients with stable PD for 3 consecutive months before performing any corrective surgery, as this provided a significant reduction in the curvature, an increase in penile length and a significant improvement of the symptoms and bother induced by PD.

The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity.

INTRODUCTION: Biothesiometry allows for evaluation of penile vibratory sensitivity and can be used as a non-invasive and rapid surrogate test of penile sexual sensitivity. However, no standardized measurement methodology currently exists. AIM: To describe and optimize a novel, standardized biothesiometry parameter-the penile sensitivity ratio (PSR). METHODS: We reviewed all biothesiometry data from men presenting to our institution from July 2013-May 2017. 3 iterations of the PSR were evaluated using the threshold for vibratory detection from a combination of different input variables including the penile glans, penile shaft, index finger, and thigh. Numerator values for the PSR included the penile glans and penile shaft, whereas denominator inputs included the index finger and thigh. PSR is inversely correlated with penile sensitivity. MAIN OUTCOME MEASURE: The primary outcome measure was the association between reported diminished penile sensitivity and PSR value. Secondary outcome measures were the association between PSR and age, diabetes, ejaculatory dysfunction, and Peyronie's disease (PD). RESULTS: Biothesiometry data were evaluated from 1,239 men. Mean age was 53.2 years (SD 14.0 years). Diabetes was present in 7.4% (n = 92); 52.0% (n = 644) had PD. Ejaculatory dysfunction was identified in 15.8% (n = 196), with 12.2% (n = 151) having premature ejaculation and 3.6% (n = 45) reporting delayed ejaculation. Decreased penile sensitivity was reported in 20.3% (n = 252). 3 PSR iterations were analyzed to identify associations with decreased penile sensation. On univariate and multivariate analysis controlling for age, diabetes, ejaculatory dysfunction, and PD, only the PSR iteration, which included data from the penile glans and finger (PSRG/F), was significantly different between patients reporting diminished penile sensitivity and those without reported diminished sensitivity (univariate P < .01, multivariate P = .03). On univariate analysis, a higher PSRG/F was associated with older age (P < .01) and diabetes (P < .01), whereas men with PD had a lower PSRG/F (P < .01). On multivariate analysis, PSRG/F remained increased for age (P < .01) and decreased for PD (P = .01); however, there was no association with diabetes (P = .12). No association existed between ejaculatory function and PSRG/F on univariate (P = .25) or multivariate analysis (P = .35). CLINICAL IMPLICATIONS: The PSR may be used as a standardized biothesiometry parameter to evaluate penile sensitivity. STRENGTH & LIMITATIONS: This study included a large cohort of men undergoing biothesiometry (n = 1,239); however, it is limited by the multifactorial nature of perceived diminished penile sensitivity. CONCLUSION: The PSR using penile glans and index finger input variables is a non-invasive, painless, office-based, standardized biothesiometry parameter that is a clinically useful tool for measuring penile sexual sensitivity. Wiggins A, Farrell MR, Tsambarlis P, et al. The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity. J Sex Med 2019;16:447-451.

Testosterone Levels Are Not Associated With Magnitude of Deformity in Men With Peyronie's Disease.

INTRODUCTION: There are some data suggesting that there is a relationship between the magnitude of Peyronie's disease (PD)-associated penile curvature and low serum testosterone. AIM: To evaluate the relationship between PD associated penile deformity and total testosterone (TT) and free testosterone (FT) levels. METHODS: We identified patients diagnosed with PD who had early morning TT measurements. Because laboratories have different reference values, we analyzed testosterone values 2 ways, as raw values and as standardized values (TT and FT values converted into z-scores for each laboratory). Deformity assessment was conducted during an intracavernosal injection-induced rigid erection. The association between T levels and magnitude of penile curvature was analyzed in a number of ways. First, an independent measure t-test tested differences in curvature degree by TT groups (low T: <300 ng/dL; normal T: ≥300 ng/dL). Second, an association was sought between T levels based on quartiles of the normal range (<300, 300-450, 450-600, and >600 ng/dL). These analyses were conducted for both TT and FT levels and using both raw and standardized T values. Third, multivariable analysis using multiple linear regression was performed in an attempt to define predictors of the degree of penile curvature. Factors entered into the model included: TT level, FT level, patient age, race (white vs other), number of co-morbidities, body mass index, presence of erectile dysfunction, duration of PD, and prostatectomy (yes vs no). MAIN OUTCOME MEASURES: The relationship between T levels and the magnitude of penile curvature. RESULTS: 184 subjects met all study criteria. Average age was 54 ± 12 years. Mean TT level was 425 ± 176 ng/dL, and mean curvature magnitude was 35° ± 19°. The percent of subjects in the first through fourth TT quartiles was 26%, 34%, 24%, and 16%. As a continuous variable, there was no association between TT levels (r = -0.01, P = .95) or FT levels (r = -0.08, P = .30) and the curvature magnitude. When examining TT groups, there was no difference in mean curvature between the low TT group and the normal TT group (35.4° ± 17° vs 34° ± 20°, P = .70). When analyzing the TT and FT levels standardized into z-scores, there was no association between degree of curvature and TT z-scores (r = -0.003, P = .95) and FT z-scores (r = -0.08, P = .43). There was also no association between testosterone levels and degree of curvature in the multivariable model. CONCLUSIONS: There does not appear to be any association between testosterone levels and the magnitude of PD-associated penile deformity. Mulhall JP, Matsushita K, Nelson CJ. Testosterone Levels Are Not Associated With Magnitude of Deformity in Men With Peyronie's Disease. J Sex Med 2019;16:1283-1289.

The Surgical Treatment of Peyronie's Disease in the Older Man: Patient Characteristics and Surgical Outcomes in Men 65 and Older.

INTRODUCTION: Surgery remains the gold standard for the correction of penile deformities secondary to Peyronie's disease (PD). Nevertheless, there is no published data on the surgical treatment of PD in older men. AIM: Considering the aging national and international population, we sought to evaluate the pre-operative characteristics and surgical outcomes of men aged 65 or older who underwent surgical treatment for PD at our tertiary care institution. METHODS: We retrospectively reviewed the charts of all men 65 years or older who underwent surgery for PD from January 2010 to September 2017. We compared men who underwent penile prosthesis implantation with straightening maneuvers (PP+SMs), tunica albuginea plication (TAP), and plaque partial excision with grafting (PEG). MAIN OUTCOME MEASURE: The main objective of this study was to find the baseline pre-operative patient characteristics and postoperative patient-reported outcomes. RESULTS: A total of 86 men with a median age of 68 years underwent surgery during the study period. 39 men underwent PP+SM (45%), 25 men a TAP (29%), and 22 men a PEG (26%). The mean curvature for all men was 59.9 ± 22.0° (range 0-105°). Those who underwent a PEG had a mean ± SD degree of curvature of 78.6 ± 16.6°, significantly higher than those who underwent PP+SM or TAP (49.1 ± 20.2° and 61.4 ± 17.4°, respectively; P < .001). Moreover, men who underwent a PEG had significantly more complex penile deformities (eg, narrowing with hinge effect) and better reported baseline erectile function compared with men who underwent PP+SM or TAP. Overall, 95% of all men reported having a functionally straight penis postoperatively with 94% engaging in penetrative intercourse at last follow-up. Overall, patient-reported satisfaction was 85% with a median follow-up of 43.5 months. CLINICAL IMPLICATIONS: Our findings suggest that the surgical treatment of PD in older men is safe, effective, and associated with high patient satisfaction. Although this represents a surgical series susceptible to selection bias, it underscores the importance of patient selection and counseling in achieving good surgical outcomes. STRENGTHS & LIMITATIONS: Our study is the first to report on outcomes of surgical treatment of PD in an elderly patient population with relatively long-term follow-up. Our limitations include a small sample size, single operating surgeon, and the lack of a younger comparison group. CONCLUSION: Despite an aging global population, surgery remains a viable and reliable option for the properly selected and counseled older men with PD. Abdelsayed GA, Setia SA, Levine LA. The Surgical Treatment of Peyronie's Disease in the Older Man: Patient Characteristics and Surgical Outcomes in Men 65 and Older. J Sex Med 2019;16:1820-1826.

Comparative Cost-effectiveness of Surgery, Collagenase Clostridium Histolyticum, and Penile Traction Therapy in Men with Peyronie's Disease in an Era of Effective Clinical Treatment.

BACKGROUND: Traditionally, surgery has been considered the gold standard treatment for Peyronie's disease (PD). Less-invasive alternatives, such as collagenase Clostridium histolyticum (CCH) and traction therapy, have been proposed and proven effective. AIM: To compare cost-effectiveness of management options for PD. METHODS: A Markov analytic model was created to compare the cost-effectiveness of treatment with a novel traction device, RestoreX (RXPTT), vs CCH vs surgery. Outcomes were derived from single-institution, prospective data of 63 men treated with RXPTT, 115 with CCH, and 23 with plication or incision and grafting. Costs were based on 2017 Medicare reimbursement and utility values from the literature. MAIN OUTCOME MEASURES: Model outcomes included complications for each treatment arm, as well as the probability of success, which was defined as ≥20% improvement in curvature. Univariable and multivariable sensitivity analyses were performed to test the robustness of the model. RESULTS: Overall success rates were 96% (surgery), 66% (CCH), and 48% (RXPTT). At 10 years after treatment, RXPTT was the most cost-effective, with mean costs per patient of $883 (RXPTT), $11,419 (surgery), and $33,628 (CCH). CCH and surgery both resulted in a gain of quality adjusted life years (QALYs) relative to RXPTT (9.44 and 9.36 vs 9.27, respectively). Sensitivity analysis demonstrated greater cost-effectiveness for surgery if lower (≤46%) rates of postoperative erectile dysfunction or length loss (≤3%). CCH became more cost-effective at lower costs (≤$16,726) or higher success rates (≥76%). On multivariable sensitivity analysis at a willingness to pay threshold of $100,000/QALY, the most cost-effective strategy was RXPTT in 49%, surgery in 48%, and CCH in 3% of simulations. At a willingness to treat threshold of $150,000/QALY, the most cost-effective treatment option was RXPTT in 33%, surgery in 55%, and CCH in 12% of simulations. CLINICAL IMPLICATIONS: In an era of value-based care, this model can guide cost-effective treatment selection on the basis of provider, patient, and payer characteristics. STRENGTHS & LIMITATIONS: The current study represents the first cost-effectiveness comparison of treatment modalities for PD and is strengthened by prospective data collection, large CCH and traction sample sizes, and robust sensitivity analyses. Consistent with cost-effective models, the model is limited by assumptions and may not apply to all scenarios. CONCLUSIONS: RXPTT represents a more cost-effective method for achieving ≥20% curvature improvement compared with surgery or CCH. Depending on treatment goals, rate of surgical complications, and willingness to pay threshold, surgery and CCH may become more cost-effective in select scenarios. Wymer K, Kohler T, Trost L. Comparative Cost-effectiveness of Surgery, Collagenase Clostridium Histolyticum, and Penile Traction Therapy in Men with Peyronie's Disease in an Era of Effective Clinical Treatment. J Sex Med 2019;16:1421-1432.

Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate. AIM: To compare the efficacy of different classes of intralesional therapy with a network meta-analysis (NMA) method. METHODS: The search was conducted using documents published in PubMed, Scopus, and Web of Science databases until September 30, 2017. We included randomized controlled trials comparing at least 1 intralesional therapy with a placebo therapy or with another drug for the treatment of PD. All intralesional therapies have been considered: collagenase Clostridium histolyticum (CCH), hyaluronic acid, verapamil, and interferon α-2b. MAIN OUTCOME MEASURE: Outcomes of the study are the mean change in penile curvature (PC) and in erectile function (EF) assessed with the International Index of Erectile Function questionnaire. RESULTS: In total, 8 comparisons matched with the inclusion criteria, which includes 1,050 patients. With regard to PC (degree) improvement, hyaluronic acid and verapamil showed worse outcomes when compared with CCH (-6.66 and -2.30) and interferon α-2b (-6.75 and -2.38). When considering improvement in EF, hyaluronic acid, verapamil and interferon α-2b showed a slight increase in mean change when compared with CCH (+2.39, +1.77, and +0.65). Moreover, verapamil and interferon α-2b showed slightly worse mean change in comparison to hyaluronic acid (+0.62 and +1.74), whereas interferon α-2b was worse than verapamil (-1.12). CLINICAL IMPLICATIONS: Based on this NMA, empirical therapy for PD should be avoided to offer the patients the best treatment in terms of level of evidence. STRENGTHS & LIMITATIONS: In this NMA, we have provided, for the first time, evidence of the efficacy between different intralesional therapies for the treatment of PD. We were not able to compare all specific outcomes (ie, pain, plaque size, patient satisfaction) of PD, because of the lack of homogeneity across relevant studies. Moreover, because of the few included studies, a meta-regression analysis of predictive factors of treatment response was not calculated. CONCLUSION: This is the first meta-analysis comparing all available intralesional treatments for PD. CCH and interferon α-2b showed the best outcome in terms of PC, whereas hyaluronic acid was most efficient in relation to EF. Russo GI, Cacciamani G, Cocci A, et al. Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis. J Sex Med 2019;16:289-299.

A snapshot of intralesional verapamil injection in the treatment of Peyronie's disease today.

Studies assessing the efficacy of intralesional verapamil injection in the treatment of Peyronie's disease have yielded mixed results. The purpose of this meta-analysis is to systematise the existing literature on the efficacy of intralesional verapamil injection when used in the treatment of Peyronie's disease. The treatment outcomes of seven different study groups identified by computerised literature search were compared with natural history outcomes and data from control groups of three studies involving placebo saline injection. An exploratory meta-analysis was performed on the data due to differing patient populations, treatment protocols, and inconsistent selection and reporting of outcomes. Intralesional verapamil injection significantly improved sexual function (p < .0005) and penile curvature (p < .005) in individuals with Peyronie's disease. Decreases in pain may be significant after therapy but are questionable. The effect of verapamil on plaque size remains less impressive (p > .05). Intralesional verapamil injection has promise to positively impact a number of clinical outcomes of Peyronie's disease; however, a large, multicentre, randomised, controlled study with reliable protocols is needed to confirm the efficacy of treatment.

Predictors of treatment success after collagenase Clostridium histolyticum injection for Peyronie's disease: development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study.

OBJECTIVE: To build a nomogram able to predict treatment success after collagenase Clostridium histolyticum (CCH) for Peyronie's disease (PD). MATERIALS AND METHODS: Between November 2016 and November 2017, we enrolled 135 patients with PD into a multicentre single-arm prospective study. All patients enrolled received CCH treatment. Success of therapy was defined as a decrease in penile curvature (PC) of ≥20° from baseline. Treatment satisfaction was assessed using a scale from 1 to 10, and high satisfaction was arbitrarily defined as a score of ≥8. Calcification level was classified as: absence of calcification; low perilesional calcification; and high calcification. RESULTS: The median (interquartile range [IQR]) patient age was 56.0 (45.0-65.0) years and the median (IQR) was PC was 30 (30.0-60.0)°. After the treatment protocol, we observed a significant median change in PC of -20.0° (P < 0.01). The median (IQR) PC improvement was 44 (28.0-67.0)%. Overall median (IQR) satisfaction score was 8.0 (7.0-9.0). Treatment efficacy was reported in a total of 77 patients (57.04%). When analysing factors associated with PC improvement after treatment, we found that baseline PC (odds ratio [OR] 1.14; P < 0.01), basal plaque (OR 64.27; P < 0.01), low calcification (OR 0.06; P < 0.01) and high calcification (OR 0.03; P < 0.01) were significant predictors of PC improvement. The c-index for the model was 0.93. CONCLUSIONS: Patients with longer PD duration, greater baseline PC and basal plaque location had a greater chance of treatment success. These results could be applied to clinical practice before external validation of our nomogram.

Penile Size Restoration With Nondegloving Approach for Peyronie's Disease: Initial Experience.

INTRODUCTION: The sliding technique (ST), commonly done with a subcoronal circumcising incision with penile degloving, has been used to restore penile size in patients with severe Peyronie's disease (PD) and erectile dysfunction, but with a potential risk of ischemic injury to the glans penis. AIM: To provide detailed surgical techniques regarding the nondegloving ventral incision and report our initial experience with this approach to perform the ST and penile prosthesis placement in patients with severe PD. METHODS: This was a retrospective review of patient outcomes after penile prosthesis placement with penoplasty for severe PD and erectile dysfunction from January 2015 to December 2017. MAIN OUTCOME MEASURES: Primary outcomes included straightening rates, penile measurement, along with immediate and late complications. Secondary outcomes include operative time and overall patient satisfaction. RESULTS: 12 Patients had significant penile atrophy and/or curvature >60 degrees and underwent inflatable penile prosthesis placement with grafting procedure. Significant penile atrophy was determined by a combination of the patient's subjective report and the surgeon's objective assessment through stretched penile length. 7 (58.3%) of those patients underwent ST, of which the last 5 had the procedure performed through a nondegloving ventral incision. Mean degree of curvature prior to ST was 66 degrees (45-90 degrees). Mean penile length gain was 2.6 cm (2.0-3.0 cm). At a mean follow-up of 15.5 months (3-31 months), only 1 patient had minimal residual curvature of 15 degrees. There were no vascular complications. CLINICAL IMPLICATIONS: This nondegloving technique theoretically maintains blood flow continuity to the glans penis by preserving the continuity of the skin, dartos fascia, and neurovascular bundle. STRENGTHS & LIMITATIONS: Strengths of this study include the novel nature of this approach, no incidence of vascular complications, and adaptability to other grafting procedures during penile prosthesis placement. Limitations include the use of 5-item International Index of Erectile Function scores to assess preoperative erectile function on PD, small population, longer incision, and a possible steep learning curve. CONCLUSION: While ischemic complications of ST and penile prosthesis implantation are rare, there are reports of ischemic injury in patients undergoing a subcoronal circumcising incision with penile degloving. The non-degloving technique with ventral incision provides for an alternative method for ST and penile prosthesis placement to maintain dartos and skin continuity to the glans penis while still allowing for adequate surgical exposure. Clavell-Hernández J, Wang R. Penile Size Restoration With Nondegloving Approach for Peyronie's Disease: Initial Experience. J Sex Med 2018;15:1506-1513.