Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease

BackgroundPeyronie’s disease (PD), defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis, is a chronic condition that afflicts 3% to 13% of the US male population; there is no current research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD.AimTo examine the efficacy and safety of CCH in the treatment of acute-phase PD.MethodsWe retrospectively reviewed the records for all patients treated with CCH for PD from April 2014 through April 2017. Patients who reported penile pain and duration of PD no longer than 12 months at presentation qualified as being in the acute phase of PD. The primary outcomes of interest were final changes in curvature after CCH treatment regardless of the number of CCH cycles received and frequency of treatment-related adverse events.OutcomesParameters of efficacy and safety were compared between acute- and stable-phase PD.ResultsA total of 162 patients were included in the study, of which 36 (22%) qualified as having acute-phase PD (group 1) and the remaining 126 (78%) qualified as having stable-phase PD (group 2). Median duration of PD was 8.5 months (range = 1–12) for group 1 and 18 months (range = 1–492) for group 2. There was no significant difference in final change in curvature between the acute and stable phases of PD (16.7° vs 15.6°; P = .654). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12 patients, 10%; P = .778).Clinical ImplicationsCCH therapy is as safe and efficacious in acute-phase PD as it is in stable-phase PD.Strengths and LimitationsThis is the first report that assesses the safety and efficacy of CCH therapy focusing on acute-phase PD. This study was composed of a large cohort of patients receiving CCH therapy in acute- and stable-phase PD. Limitations include bias associated with retrospective studies, a small sample, and a single-center setting.ConclusionsAlthough CCH is not clearly indicated for treatment during the acute phase of PD, these results suggest that CCH use during this phase can be effective and safe. There was no statistically significant difference in final change in curvature or treatment-related adverse events after CCH therapy delivered between the acute and stable phases of PD.Nguyen HMT, Anaissie J, DeLay KJ, et al. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease. J Sex Med 2017;14:1220–1225.     

Outcomes of RestoreX Penile Traction Therapy in Men With Peyronie’s Disease: Results From Open Label and Follow-up Phases

BackgroundA randomized, controlled clinical trial evaluating the efficacy of RestoreX traction therapy in men with Peyronie’s disease (PD) has been completed, with the 3-month results previously reported. The present study presents outcomes from the open-label and follow-up phases of the original trial.AimTo report 6-month (open-label phase) and 9-month (follow-up phase) outcomes from a randomized, controlled trial (NCT03389854).MethodsA randomized controlled trial was performed from 2017 to 2019 in 110 all-comer men with PD. Men were randomized 3:1 to RestoreX (PTT) or no therapy (control) for 3 months, followed by 3-month open-label and follow-up phases. Key outcomes included adverse events (AEs), changes in penile curvature and length, erectile function, and standardized and nonstandardized assessments of PD.OutcomesThe primary outcomes are safety, penile length, penile curvature, Peyronie’s Disease Questionnaire, International Index of Erectile Function, and satisfaction.Results6-month (n = 64) and 9-month (n = 63) outcomes were reported, with a mean duration of PTT use of 31.1 minutes. No significant AEs were reported, with temporary erythema and discomfort being most common and resolving within minutes. On intent-to-treat analysis, control-to-PTT men experienced significant length (1.7–2.0 cm) and curvature improvements (18–20%). PTT-to-PTT men also achieved additional length (0.6–0.8 cm) without further curvature improvements. An as-treated analysis of PTT use ≥15 minute/day demonstrated 2.0- to 2.3-cm length gains (largest of any PTT to date) and 18–21% curve improvement. All sexual function domains of the International Index of Erectile Function and Peyronie’s Disease Questionnaire were significantly improved (except orgasmic domain). 95% of men treated for 6 months experienced length gains (mean 2.0–2.2 cm), and 61% had curve improvements (16.8–21.4° [32.8–35.8%]). RestoreX was preferred 3–4:1 over all other PD treatments, and 100% preferred it over other PTT devices.Clinical ImplicationsUse of RestoreX 30 minutes daily results in significant length and curve improvements in PD men without significant AEs.Strengths & LimitationsStrengths include largest randomized study of PTT, blinded assessments, and inclusion of all-comers with few restrictions; limitations include sample size that precludes comparisons between treatment cohorts and lack of long-duration (>3–9 hours) treatment arm.ConclusionPTT with RestoreX results in significant improvements in length, curve, and subjective and objective measures of sexual function without significant AEs. RestoreX PTT represents a safe, conservative, low-cost option for managing men with PD.Joseph J, Ziegelmann M, Alom M, et al. Outcomes of RestoreX Penile Traction Therapy in Men With Peyronie’s Disease: Results From Open Label and Follow-up Phases. J Sex Med 2020;17:2462–2471.     

Increased Risk of Incident Disease in Men with Peyronie’s Disease: Analysis of U.S. Claims Data

Background

The subsequent health risks associated with Peyronie’s disease (PD) are unknown.

Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie’s Disease

BackgroundPrevious studies of penile traction therapy (PTT) devices have demonstrated limited/no efficacy when combined with intralesional therapies for Peyronie’s disease (PD). Recently, randomized data have demonstrated the efficacy of a novel PTT device, RestoreX, developed in cooperation with the Mayo Clinic, in men with PD.AimTo assess the safety and efficacy of treatment with the RestoreX device plus collagenase Clostridium histolyticum (CCH) compared with CCH alone and CCH with other PTT devices.MethodsA prospective registry has been maintained of all men undergoing CCH injections for PD between March 2014 and January 2019. Assessments were performed at baseline, during each series, and after completion of treatment. Those completing therapy (8 injections or sooner if satisfied) were categorized into group 1 (CCH alone), group 2 (CCH plus any PTT device other than RestoreX), or group 3 (CCH plus RestoreX).OutcomesChanges in penile length, curvature, and subjective perception and the occurrence of adverse events.ResultsOf 287 men with data on PTT use, 113 had completed therapy with all objective data available and compose the current cohort. Baseline demographic and pathophysiological variables were similar among the 3 groups except penile length and previous PD medications. Following treatment, group 3 demonstrated significantly greater improvements in curvature (mean, 20.3°/31% for group 1, 19.2°/30% for group 2, and 33.8°/49% for group 3), length (-0.7 cm/-4%, -0.4 cm/-2%, and +1.9 cm/+17%, respectively), and subjectively estimated curvature improvement (44%, 32%, and 63% respectively), despite shorter daily PTT use (0.9 vs 1.9 hours/day). Group 3 was more likely than the other groups to experience ≥20°, ≥20%, and ≥50% curvature improvements, ≥1 cm length gain, and ≥20% length improvement. All results were statistically significant for group 3 versus groups 1 and 2, but not between groups 1 and 2, even after controlling for baseline features and isolating a subset of ≥3 hours/day PTT use (group 2). Group 3 was 6.9 times more likely to achieve ≥20° curvature improvement, and 3.5 times more likely to achieve ≥50% curvature improvement, and 10.7 times more likely to experience ≥20% length improvement. Adverse events were similar among the 3 groups.Clinical ImplicationsUse of the RestoreX device enhances mean curvature outcomes by 71% and increases penile length in men with PD receiving CCH therapy.Strengths & LimitationsStudy strengths include a prospective registry, consistent assessments, the largest single-site series with complete posttreatment outcomes reported to date, the largest PTT series reported to date, and a true-to-life clinical design. Limitations include the nonrandomized methodology and single-site setting.ConclusionThe combination of RestoreX and CCH is associated with significantly greater curvature and length improvements compared with CCH alone or CCH with other PTT devices.Alom M, Sharma KL, Toussi A, et al. Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie’s Disease. J Sex Med 2019;16:891–900.     

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

IntroductionThere are some data suggesting that there is a relationship between the magnitude of Peyronie’s disease (PD)–associated penile curvature and low serum testosterone.AimTo evaluate the relationship between PD associated penile deformity and total testosterone (TT) and free testosterone (FT) levels.MethodsWe 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 MeasuresThe relationship between T levels and the magnitude of penile curvature.Results184 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.ConclusionsThere 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.     

Peyronie’s Disease and the Female Sexual Partner: A Comparison of the Male and Female Experience

BackgroundPeyronie’s disease (PD) is characterized by penile pain, deformity, and sexual dysfunction, often resulting in an impaired sexual experience and significant psychological bother for the patient. However, there are limited data on the impact of PD on female sexual partners (FSPs).AimTo compare the psychosexual experience of men with PD and their FSPs.MethodsWe retrospectively reviewed all prospectively enrolled men and their FSPs who presented for initial PD evaluation to our sexual health clinic from July 2018 to February 2020. All men completed a PD-specific survey and the PD questionnaire (PDQ). If the patient was accompanied by an FSP during initial evaluation, she completed the PDQ for Female Sexual Partners and Female Sexual Function Index. We further queried our database that included information on patient demographics and clinical characteristics.OutcomesThe main outcome of this study is retrospective comparison of responses with the PDQ and PDQ for Female Sexual Partners.ResultsData were available for 44 men with PD (median age, 56 years; interquartile range, 49–63) and their FSPs (median age, 54 years; interquartile range, 50–61). The majority of men presented in the chronic phase (35 of 44, 79.5%), and median objective composite curvature was 75° (interquartile range, 50–90°). Owing to PD, female and male partners reported similar difficulty with vaginal intercourse (VI) (74.3% vs 81.5%, P = .555), decreased frequency of VI (70.6% vs 85.2%, P = .228), and at least moderate discomfort/pain with VI (48.6% vs 33.3%, P = .232). FSPs were “very” or “extremely” bothered by the appearance of their partner’s erect penis less often than male partners (20.0% vs 59.3%, P < .001). FSPs were “very” or “extremely” bothered by their partner’s PD during VI less often than men with PD (32.3% vs 65.2%, P = .017). Few FSPs (22.9%) had “severe” or “very severe” concern with damaging their partner’s penis during VI.Clinical ImplicationsThe sexual experience for men with PD and their FSPs differs, thus emphasizing the importance of active engagement of both men with PD and FSP during initial PD evaluation.Strengths and LimitationsThis initial study draws data from a single, high-volume men’s health clinic with a limited sample size. Survey responses may have been shared by patients with PD and their FSPs.ConclusionPD impacts the sexual experience for both men and FSPs. A similarly large proportion of men with PD and FSP noted decreased frequency of and difficulty with vaginal intercourse. Yet, FSPs were less bothered by the appearance of the erect penis and the deformity during VI compared with men.Farrell MR, Ziegelmann MJ, Bajic P, et al. Peyronie’s Disease and the Female Sexual Partner: A Comparison of the Male and Female Experience. J Sex Med 2020;17:2456–2461.     

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

BackgroundTraditionally, 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.AimTo compare cost-effectiveness of management options for PD.MethodsA 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 MeasuresModel 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.ResultsOverall 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 ImplicationsIn an era of value-based care, this model can guide cost-effective treatment selection on the basis of provider, patient, and payer characteristics.Strengths & LimitationsThe 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.ConclusionsRXPTT 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.     

Validity and Reliability of a Smartphone Application for the Assessment of Penile Deformity in Peyronie’s Disease

IntroductionAvailable methods to evaluate men with Peyronie's disease (PD) are limited by the inability to accurately and reproducibly measure penile deformity.AimThe study aims to evaluate the performance of a smartphone application for the measurement of penile curvature and narrowing.MethodsA smartphone application, the University of Washington Peyronie's Examination Network (UWPEN), was developed for this purpose. To assess penile curvature, 15 single cylinders of malleable penile prostheses were molded to varying curvature angles. Three blinded observers nonsequentially measured the angle of curvature for each prosthetic cylinder using a protractor, goniometer, and UWPEN. To assess girth narrowing, six clay models of the penile shaft were constructed to represent conditions of normal, partial hourglass, circumferential hourglass, and pencil narrowing. Girth was measured using a ruler and UWPEN by the same blinded observers.Main Outcome MeasuresStatistical analyses compared intertest, interobserver, and intraobserver reliability using the interclass correlation coefficient (ICC). An ICC above 0.75 indicates excellent reproducibility among measurements.ResultsIntertest reliability for angle measurements yielded an ICC for the three methods of 1.000. Separately, the ICC for UWPEN vs. the goniometer and protractor was 0.999 and 0.999, respectively. The interobserver ICC for UWPEN, goniometer, and protractor was 0.998, 0.999, and 1.000, respectively. Intertest reliability for girth narrowing measurements yielded an ICC of 0.991. The interobserver ICC for girth narrowing for UWPEN and the ruler was 0.978 and 0.986, respectively. Intraobserver ICC for angle measurements and girth narrowing showed high reliability for all observers and methods.ConclusionsThe performance of UWPEN is comparable with and highly correlated with angle measurements obtained from the goniometer and protractor as well as with girth narrowing measurements obtained from a ruler. Measurements are reproducible among different observers. UWPEN may provide a noninvasive, accurate, reliable, and widely accessible method to characterize and track PD over time. Hsi RS, Hotaling JM, Hartzler AL, HoltSK, and Walsh TJ. Validity and reliability of a smartphone application for the assessment of penile deformity in Peyronie's disease.     

Effect of Penile Traction and Vacuum Erectile Device for Peyronie’s Disease in an Animal Model

BackgroundPenile traction therapy with the use of a traction device (TD) or vacuum erectile device (VED) has been studied as local modalities for Peyronie’s disease (PD).AimTo identify changes of penile curvature, erectile function, and possible cellular and molecular mechanisms between the TD and VED in a rat model of PD.MethodsPeyronie’s plaque was induced in 30 adult male rats. Then, rats were randomly divided into control (PD without treatment), VED, and TD groups. In the VED group, vacuum pressure was applied to the cylinder to induce penile engorgement inside the cylinder for 1 minute. The penis was allowed to deflate completely for another 1 minute. This was repeated for five cycles (inflate and deflate). In the TD group, the rat penis was straightened by a suspended tension gauge at the same tension by clamping the prepuce. This was performed three times per day at 20 minutes per session, with 5-minute intervals between sessions. The entire treatment duration was 4 weeks.OutcomesPenile curvature, intracavernosal pressure, and mean arterial pressure were measured. Immunohistochemistry for α-smooth muscle actin, transforming growth factor-β1 and mothers against decapentaplegic homolog 2/3 were performed.ResultsThe TD and VED groups had less penile curvature compared with the control group (15.3 ± 5.3° for TD, 28.4 ± 6.8° for VED, 38.6 ± 10.5° for control; P < .001 for TD vs control, P < .05 for VED vs control). The TD group also had less penile curvature compared with the VED group (P < .05). The VED group had a higher ratio of intracavernosal pressure to mean arterial pressure compared with the two other groups (0.56 ± 0.10 for VED, 0.38 ± 0.06 for TD, 0.32 ± 0.07 for control; P < .001). The immunohistochemistry results showed the VED group had more preserved α-smooth muscle actin with less transforming growth factor-β1 and mothers against decapentaplegic homolog 2/3 than the TD and control groups in the corpus cavernosa.Clinical TranslationVarious benefits can be observed with the TD and VED for the treatment of PD.Strengths and LimitationsThis study explored the mechanism and benefits of TD and VED therapies for the treatment of PD. The rat model might not represent the human condition.ConclusionPenile traction therapy with the TD or VED is beneficial to decrease penile curvature in animal models of PD. The underlying mechanism could be related to antiapoptosis, antifibrosis, and smooth muscle preservation.Lin H, Liu C, Wang R. Effect of Penile Traction and Vacuum Erectile Device for Peyronie’s Disease in an Animal Model. J Sex Med 2017;14:1270–1276.     

The Partner’s Presence in the Sex Research Lab Differentially Affects Sexual Arousal in Women and Men

IntroductionThe present study addressed the ecological validity of the individual‐focused experimental paradigm in sex research.AimThe aim of this study was to investigate the effect of partner presence vs. absence in the laboratory testing situation, and of manipulation of attentional focus, on genital and subjective sexual arousal of healthy women and men.MethodsSexually functional heterosexual men (n = 12) and women (n = 12) and their partners participated in this study. During partner presence, the partner sat opposite to the participant; self‐focused attention was experimentally manipulated by introducing, respectively, a semi‐reflecting glass pane, and a wall‐mounted camera.Main Outcome MeasuresPerceived state self‐focused attention and genital and subjective sexual arousal during presentation of audiovisual erotic film stimuli were assessed.ResultsPartner presence resulted in higher perceived self‐focus (η_p² = 0.22) and lower genital responses to erotic stimulation (η_p² = 0.21). The interaction of partner presence and increased self‐focused attention differentially affected genital arousal in female and male participants (η_p² = 0.38). The mean genital response in men was lower during private self‐focus than during non‐self‐focus with the partner present but was higher during private self‐focus with the the partner absent (η_p² = 0.23). The genital response in women to public self‐focus was lower than to private self‐focus and to non‐self‐focus with their partner present (η_p² = 0.36). With the partner absent, the genital response in women to private self‐focus was lower than to non‐self‐focus (η_p² = 0.23). Retrospective subjective arousal of women was higher with partner present (M = 3.2) than with partner absent (M = 2.9), whereas men reported higher retrospective subjective arousal with their partner absent (M = 3.5) than present (M = 3.1).ConclusionsThese findings suggest that mere presence of the partner impacts the sexual response differentially in women and men. Enhancing the ecological validity of the individual‐based laboratory paradigm for sex research warrants closer examination in future research. van Lankveld J, Hubben D, Dewitte M, Dingemans ME, den Butter C, and Grauvogl A. The partner's presence in the sex research lab differentially affects sexual arousal in women and men. J Sex Med 2014;11:697–708.     

Penile Sensory Changes After Plaque Incision and Grafting Surgery for Peyronie’s Disease

Introduction

Plaque incision and grafting (PIG) for Peyronie’s disease (PD) is not devoid of complications such as erectile dysfunction and penile sensory changes.

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.