Treatment of Peyronie's Disease With Collagenase Clostridium histolyticum and Vacuum Therapy: A Randomized,Open-Label Pilot Study

BackgroundCollagenase Clostridium histolyticum (CCH) is indicated for the treatment of penile curvature in adult men with Peyronie's disease (PD) with palpable plaque and curvature deformity of at least 30° at the start of therapy.AimTo evaluate the efficacy and safety of CCH plus vacuum-pump therapy with and without penile modeling for the management of PD.MethodsAdult men with PD and penile curvature of at least 30° were randomly assigned to receive CCH 0.58 mg plus vacuum therapy alone (n = 15) or with penile plaque modeling (n = 15). Patients received no more than four treatment cycles (cycle = ∼6-week duration), each consisting of two intralesional injections of CCH administered 24 to 72 hours apart. Vacuum therapy was applied twice daily from 14 days after the second injection of each cycle until the following cycle. Modeling was performed 24 to 72 hours after the second injection of each cycle.OutcomesThe primary end point was change in penile curvature from baseline to week 36; additional end points included changes in Peyronie's Disease Questionnaire (PDQ) domain scores, composite response (≥20% decrease in penile curvature and decrease in PDQ bother score ≥ 1 point), and global response (small but important, moderate, or much improvement in the Global Assessment of PD).ResultsAt week 36, improvement in penile curvature from baseline was similar in the two groups (mean change from baseline = −23.7° [SD = 10.9] for CCH + vacuum + modeling and −23.3° [SD = 7.2] for CCH + vacuum; between-group difference = −0.3°, 95% CI = −7.3 to 6.6). Improvements in most PDQ domains, including bother, were observed from baseline to week 36 in the two groups. Most patients were composite (66.7% and 84.6% with CCH + vacuum + modeling and CCH + vacuum, respectively) and global (86.7% and 92.3%, respectively) responders. The most common adverse events were penile contusion, penile swelling, and penile pain.Clinical ImplicationsVacuum-pump therapy administered alone or in combination with modeling after CCH treatment could improve PD symptoms.Strengths and LimitationsThis was a pilot study with a small sample and limited follow-up duration.ConclusionCCH and vacuum-pump therapy (alone or combined with modeling) could be an appropriate consideration for men with PD and warrants further investigation.Ralph DJ, Abdel Raheem A, Liu G. Treatment of Peyronie's Disease With Collagenase Clostridium histolyticum and Vacuum Therapy: A Randomized, Open-Label Pilot Study. J Sex Med 2017;14:1430–1437.     

Clinical Safety and Effectiveness of Collagenase Clostridium Histolyticum Injection in Patients with Peyronie's Disease: A Phase 3 Open‐Label Study

IntroductionCollagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration‐approved, intralesional treatment for Peyronie's disease (PD).AimThe aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD.MethodsThis phase 3, open‐label study enrolled subjects who were CCH‐naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24–72 hours apart, and plaque modeling 24–72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles.Main Outcome MeasuresThe co‐primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0–16) from baseline to week 36.ResultsOf the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronie's Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment‐related AEs, two penile hematomas and one corporal rupture; all resolved with treatment.ConclusionsPotentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open‐label study support the use of CCH in the treatment of PD. Levine LA, Cuzin B, Mark S, Gelbard MK, Jones NA, Liu G, Kaufman GJ, Tursi JP, and Ralph DJ. Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: A phase 3 open‐label study. J Sex Med 2015;12:248–258.     

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.     

Surgical Correction of Persistent Peyronie's Disease Following Collagenase Clostridium Histolyticum Treatment

IntroductionCollagenase clostridium histolyticum (CCH) is an Food and Drug Administration‐approved intralesional injection for treatment of Peyronie's disease (PD) that has been shown to reduce penile curvature deformity and PD symptom bother in phase 2b and phase 3 placebo‐controlled clinical trials. For some patients, nonsurgical treatment with CCH may not sufficiently improve penile curvature, and surgical correction may be pursued following CCH therapy.AimThis study aims to examine intraoperative and postsurgical outcomes of surgical correction of persistent penile curvature in patients with PD who had previously received CCH.MethodsRetrospective chart review was used to identify patients with PD who had received CCH intralesional injection within either the phase 2b or phase 3 CCH clinical trials and then underwent surgical correction due to remaining penile curvature. Surgical techniques used were partial plaque excision and grafting (PEG) and/or tunica albuginea plication (TAP).Main Outcome MeasuresPrimary assessments included pre‐ and postsurgery penile curvature, erectile rigidity, stretched penile length, intraoperative time, and occurrence of adverse events.ResultsSeven men were identified who underwent surgical straightening with TAP or PEG following CCH treatment. Mean number of days from the final CCH injection to surgery was 182 (standard deviation 118; median 127 days). Average penile curvature prior to surgical straightening was 58°. No anatomical difficulties or complications secondary to the effects of prior CCH treatment occurred during surgery. Intraoperative time was representative of standard TAP and PEG surgeries (range 88–146 minutes). All men reported penile curvature <20° postsurgery. One patient experienced a postsurgery subgraft hematoma that required aspiration. There were no postsurgery reports of decreased penile sexual sensation and no occurrence of vascular compromise or decreased penile rigidity.ConclusionThis initial case series supports the hypothesis that prior CCH treatment is not a contraindication to PEG or TAP surgery in the treatment of penile curvature in patients with PD. Levine LA and Larsen SM. Surgical correction of persistent Peyronie's disease following collagenase clostridium histolyticum treatment. J Sex Med 2015;12:259–264.     

Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes

BackgroundA subset of patients with Peyronie's disease (PD) treated with collagenase clostridium histolyticum (CCH) experience persistent bother and some require surgery.AimWe characterize patients experiencing persistent bother after CCH treatment and identify associations and predictors of surgical intervention/outcomes.MethodsWe retrospectively identified patients with PD from October 2014 to October 2019 and identified those presenting with persistent bother after CCH treatment by other urologists. Intracavernosal injection and penile Doppler ultrasonography were performed, and subsequent interventions/outcomes were recorded. Baseline characteristics were compared with Student t-test and chi-square test. Predictors of surgical intervention and complications were assessed using multivariable logistic regression.OutcomesThe primary outcome was surgery after CCH treatment. Secondary outcomes included worsened erectile function, sensory deficits, and penile length change.ResultsOf 573, 67 (11.7%) patients with PD had undergone prior CCH treatment with median 6 injections (range 2–24). Mean post-CCH PD Questionnaire bother score was 10.1 (SD: 3.1), and total International Index of Erectile Function-5 was 15.3 (SD: 8.7). Mean PD duration was 27.8 (SD: 35.7) months, with a mean composite curvature (MCC) of 69.0° (SD: 33.8) measured after injection. Of 67, 44 (65.7%) patients had MCC >60°. Of 67, 52 (77.6%) patients had indent, narrowing, or hourglass and 26 (38.8%) had hinge effect (buckling of the erect penis with axial pressure) on examination. Calcification was identified in 26 of 67 (38.8%) patients, with grade 3 calcifications comprising 6 of 23 (26.1%) patients. Of 67, 33 (49.3%) patients underwent surgery, with 20 (60.1%) undergoing partial plaque excision and grafting with/without tunica albuginea plication, 6 (18.2%) undergoing tunica albuginea plication alone, and 7 (21.2%) undergoing penile prosthesis with plaque incision and grafting. Surgical patients had greater mean curvature (82.6 vs 55.4, P = .001) and were more likely to have hinge (54.5% vs 20.6%, P = .005). On multivariable analysis, MCC ≥60° predicted patient’s decision for surgery (odds ratio: 2.99, P < .01, 95% confidence interval: 1.62–4.35). There were no associations between surgical complications and number of injections or CCH-associated adverse events.Clinical ImplicationsPatients presenting with persistent bother after CCH treatment often have narrowing and calcifications (despite calcifications being a contraindication to CCH treatment), and those who have hinge or severe curvature are more likely to undergo surgery with low rates of complications.Strengths/LimitationsThis study's generalizability is limited by selection bias, but useful data are provided for patient counseling.ConclusionPatients with persistent bother after CCH treatment had high rates of indentation/narrowing, plaque calcifications, and MCC >60° at completion of CCH treatment. Surgical intervention is more common with hinge and is safe and feasible in these patients, with low rates of complications. These findings suggest possible negative prognostic factors for CCH treatment, which merit further investigation.Bajic P, Wiggins AB, Ziegelmann MJ, et al. Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes. J Sex Med 2020;17:1005–1011.     

Baseline Characteristics from an Ongoing Phase 3 Study of Collagenase Clostridium Histolyticum in Patients with Peyronie's Disease

IntroductionPeyronie's disease (PD) is a localized penile collagen disorder of the tunica albuginea associated with significant physical deformity and psychological impairment. Current understanding of pretreatment characteristics in patients with chronic PD is limited by small samples, varied quality of assessments, and the lack of a PD‐specific, validated measure of the psychosexual impact of PD.AimsReporting baseline demographic and disease characteristics of the large multinational cohort of subjects with chronic PD who participated in the collagenase clostridium histolyticum (CCH, an investigational intralesional injection and minimally invasive intervention) phase 3 clinical study program. Findings from well‐defined assessments, including the Peyronie's Disease Questionnaire (PDQ), the first validated PD‐specific patient‐reported measure of psychosexual impact, are reported.MethodsSubjects included men ≥18 years old with PD symptoms ≥12 months and penile deformity between 30° and 90°. Analysis data included demographics, disease history, and psychosexual impact.Main Outcome MeasuresPenile deformity, disease symptoms, the International Index of Erectile Function, and the PDQ were assessed.ResultsEight hundred thirty‐two subjects were enrolled from 64 sites across the United States and Australia. The mean age was 57.7 years; mean PD duration was 4.1 years. The majority of subjects had penile deformity ≤60° (77.3%); mean penile deformity was 50.5°. Subjects reported having intercourse a mean of 10.2 times in the previous 3 months, 70.8% reported difficulty in performing vaginal intercourse, and 80.4% reported less frequent vaginal intercourse. Approximately 71.5% of subjects with severe (>60°) and 58.1% of subjects with mild/moderate (≤60°) penile deformity were “very bothered” or “extremely bothered” upon last look at their erect penis (P = 0.0041), as measured by the PDQ.ConclusionsThese data add to the body of knowledge regarding the clinical impact of chronic phase PD, including the PD-specific patient-reported psychosexual symptoms, using a large multinational chronic PD cohort in the CCH phase 3 clinical program. Gelbard M, Hellstrom WJG, McMahon CG, Levine LA, Smith T, Tursi J, Kaufman G, and Goldstein I. Baseline characteristics from an ongoing phase 3 study of collagenase clostridium histolyticum in patients with Peyronie's disease. J Sex Med 2013;10:2822–2831.     

Evaluating the Impact of Penile Girth Discrepancy on Patient Bother in Men With Peyronie's Disease: An Observational Study

BackgroundMen with Peyronie's disease (PD) may experience penile narrowing. Little data on penile girth changes and their psychosocial impact exist.AimTo assess girth discrepancy in men with PD and its association with patient bother.MethodsThis was a retrospective observational study. All patients with PD at our institution who were seen in the sexual medicine clinic and who completed 3 validated instruments the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire, and a depression questionnaire, the Center for Epidemiologic Studies Depression Scale (CES-D), and a curvature assessment were included. Patient and PD characteristics are described. Associations of instability and bother to girth differences are assessed. 2 outcomes for girth differences are classified as (i) girth difference of ≥ 1 cm vs less and (ii) girth differences of ≥10% vs less. Unadjusted and adjusted effects of PD and patient characteristics are assessed on the outcome of high bother using logistic regression models.OutcomesThe main outcomes of this study were penile girth changes, instability, and questionnaire scores. High bother was defined as a PDQ bother score of ≥9.ResultsA total of131 men had midshaft curvature and were the focus of the study. Their mean age was 59 ± 9 (range 31–78) years. PD duration was 16 ± 25 (range 1–180) months, with a mean degree of primary curvature of 37 ± 20^o. Mean girth difference between base and point of maximum curvature was 0.78 ± 0.53 cm equating to a mean girth difference at point of maximum curvature of 6 ± 4%. Instability was present in 53% of men. There were 54 men with a girth difference of ≥ 1 cm and 23 men with a ≥10% change in girth. There was no difference in CES-D, SEAR, or PDQ domain scores or high bother in men with significant girth changes. Univariable analysis of predictors of high bother included the degree of curvature (odds ratio [OR]: 1.06; P < .001), instability (OR 6.62; P < .001), CES-D sum (OR 1.09; P = .002), and SEAR score (OR 0.96; P = .001). On multivariate analysis, only the degree of primary curvature was predictive of high bother (OR 1.06; P < .001).Clinical ImplicationsPenile girth changes have little impact on overall psychosocial well-being. The degree of penile curvature is the primary predictor of patient bother.Strengths and LimitationsStrengths include a large patient population and use of validated questionnaires. Limitations include single-center, retrospective study and subjective instability grading.ConclusionsPenile girth discrepancy in men with PD has limited psychosocial impact. Clinically significant bother was associated with the degree of primary curvature.Salter CA, Nascimento B, Terrier, JE, et al. Evaluating the Impact of Penile Girth Discrepancy on Patient Bother in Men With Peyronie's Disease: An Observational Study. J Sex Med 2020;17:1560–1565.     

Correlation of Degree of Penile Curvature between Patient Estimates and Objective Measures among Men with Peyronie's Disease

IntroductionAmong men with Peyronie's disease (PD), the degree of penile curvature has significant implications on psychological well-being, sexual function, treatment planning, and posttherapy evaluations.AimThe primary objective of the current study was to correlate patients' estimates of penile angulation with objective measures.Main Outcome Measures(i) Proportion of patients over- or underestimating their actual degree of curvature; and (ii) degree differences between patient estimates and objective measures of penile curvature.MethodsAt baseline, patients with established PD were asked to provide a “best estimate” of their degree of penile curvature. Objective measures of penile angulation were then performed using standardized photographs and protractor-based measurement of penile curvature during full erection. Correlations were performed between patient estimates of penile curvature and objective measures of penile angulation.ResultsEighty-one men with established PD and a mean age of 52 years (range: 20–72 years) were prospectively evaluated. Mean duration of disease was 33 months (range: 6–276 months), and mean plaque size was 1.4 cm ± 0.1 standardized error (SE). The proportion of patients with dorsal, lateral, and ventral curvatures was 39%, 57%, and 4%, respectively. Patient estimates of baseline penile curvature (mean 51 degrees ± 3.1 SE) differed significantly from objective measurements (mean 40 degrees ± 2.4, P = 0.001). A significantly higher proportion of patients overestimate their actual degree of penile curvature (54% overestimate, 26% underestimate, and 20% are accurate within 5 degrees, P = 0.002). Compared with objective measures, patients' estimates of degree of penile curvature differed by an average of 20 degrees ± 2.2 SE.ConclusionsPatients with PD tend to overestimate their degree of penile curvature. Objective measurement of penile angulation is necessary to accurately counsel patients regarding disease severity, recommend appropriate treatment strategies, and objectively evaluate outcomes following therapy. Bacal V, Rumohr J, Sturm R, Lipshultz LI, Schumacher M, and Grober ED. Correlation of degree of penile curvature between patient estimates and objective measures among men with Peyronie's disease. J Sex Med 2009;6:862–865.     

Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men

BackgroundIt is currently unclear if men with Peyronie's Disease (PD) who achieve minimal benefits with the first 2 series of Collagenase Clostridium Histolyticum (CCH) injections should continue with additional injections.AimTo analyze curvature improvements from the final two series of CCH injections based on amount of improvement during the first 2 series.MethodsA prospective registry was analyzed of all men undergoing CCH injections for PD at a single institution. Men were included if they had completed a full 4 series (8 injections) of CCH and had baseline, interval (after 2 series), and/or final (after 4 series) curvature assessments available. Men were stratified into cohorts using baseline-to-interval assessments of ≤10° (or ≤20%) and >10° (or >20%), and improvements were compared using interval-to-final assessments.OutcomesThe primary outcome was interval-to-final curvature improvements stratified by ≤10°/>10° or ≤20%/>20% improvements achieved during the baseline-to-interval period. Secondary outcomes included analyses of demographic and pathophysiologic variables to determine associations with significant improvements during the final 2 CCH series.ResultsA total of 296 PD men were identified as receiving at least one CCH injection, of whom 175 had baseline-to-interval, 84 interval-to-final, and 115 with baseline-to-final measurements. Mean age was 56.6, PD duration 28.6 months, baseline curvature 63.4°, hourglass deformity 36.2%, and calcification 20%. Mean overall curve improvement was ?21.5° (33.1%). Among men who experienced ≤20% improvements after 2 series, the mean subsequent curvature change was -24.6% during the final two series (vs +4.3% of those with >20% initial improvement, P< .001), and they were 2.7x more likely to experience >20% subsequent curve improvements. Thirty-one percent of those who achieved >10° during the first 2 series experienced benefits during the final 2 series compared to 70% of men who had ≤10° improvement initially. No demographic or pathophysiological variables predicted likelihood for improvements during the final 2 series of injections.Clinical ImplicationsMen who fail to achieve significant benefits with 2 series of CCH injections may benefit from completing the final 2 series.Strengths and LimitationsStrengths including a relatively large, prospective series. Limitations include a single center, nonrandomization, nonblinded assessments, and restriction to men who completed eight injections.ConclusionsIn the current series, approximately 2/3 of men who fail to achieve >10° or 20% curve improvements with an initial 2 series of CCH injections achieved >10° or 20% improvements with the subsequent 2 series.Alom M, Burgon H, Ziegelmann M, et al. Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men. J Sex Med 2021;18:1092–1098.     

Comparative Analysis of Tunical Plication vs. Intralesional Injection Therapy for Ventral Peyronie's Disease

IntroductionApproximately 10% of Peyronie's disease (PD) patients present with ventral curvatures and, as such, there is a paucity of data describing the optimal approach for treatment.AimThis study aims to compare the outcomes of surgery (tunical plication [TP]) and intralesional injection (ILI) therapy (interferon‐α2b) in men with ventral PD.Materials and MethodsRetrospective data were collected from two centers: Tulane University (ILI) and Technical University of Munich (TP). Collected variables included patient demographics, pre‐ and post‐treatment sexual function, rigorous penile measurements (curvature, length, and penile vascular findings), and post‐treatment outcomes.ResultsA total of 35 patients with ventral PD (21 ILI and 14 TP) were included in the study. There were no significant differences between the two groups prior to the interventions. There was a significantly better improvement in mean curvature with TP (46.4 degrees) as compared with ILI (9.3), P < 0.0001. TP was also associated with a significantly higher rate of ≥20% improvement in curvature as compared with ILI (100% vs. 67%, P = 0.027). Although there was no significant difference in post‐treatment change in Sexual Health Inventory for Men (SHIM) scores between the groups, 36% of the ILI patients noted an improved SHIM score as compared with none in the TP group. Erect penile length was preserved or improved in 67% of the ILI group vs. 14% of the TP group, P = 0.005.ConclusionsTP confers a better overall improvement in penile curvature as compared with ILI in patients with ventral PD. Preserved or improved erect penile length and SHIM scores may be observed in patients undergoing ILI. Yafi FA, Hatzichristodoulou G, Knoedler CJ, Trost LW, Sikka SC, and Hellstrom WJG. Comparative analysis of tunical plication vs. intralesional injection therapy for ventral Peyronie's disease. J Sex Med 2015;12:2492–2498.     

Responsiveness of the Peyronie's Disease Questionnaire (PDQ)

IntroductionIn order to reliably assess treatment effectiveness, patient-reported outcome instruments must demonstrate adequate psychometric properties.AimTo assess the responsiveness of the Peyronie's Disease Questionnaire (PDQ) using data from two Phase 3 trials of collagenase clostridium histolyticum for Peyronie's disease (PD).MethodsBoth trials recruited adult males with PD who were in a stable relationship with a female partner for at least 3 months. Patients completed the PDQ, International Index of Erectile Function (IIEF), and a global assessment of PD (GAPD) questionnaire at baseline and Weeks 24 and 52. Anchor- and distribution-based methods were used to evaluate the responsiveness of the PDQ.Main Outcome MeasurePeyronie's Disease Questionnaire.ResultsThe number of men available with baseline and Week 52 data was 267 for Study 1 and 270 for Study 2. The mean age was 58.0 for Study 1 and 57.4 for Study 2; the majority were white (95.2% and 97.3%, respectively). Mean PDQ subscale change scores from baseline to Week 52 for both studies ranged from −1.5 to −4.6 (P < 0.0001). In Study 1, effect sizes were moderate to large on the Psychological and Physical Symptoms (−0.56) and Symptom Bother subscales (−0.84). For patients with penile pain at baseline, the effect size was large (−1.05) for the Penile Pain subscale. Similar effect sizes were seen in Study 2. The Psychological and Physical Symptoms and Symptom Bother subscales significantly discriminated patient improvement ratings of GAPD and degree of penile curvature at Weeks 24 and 52.ConclusionsThe PDQ is highly responsive to change in men with PD. Coyne KS, Currie BM, Thompson CL, and Smith TM. Responsiveness of the Peyronie's Disease Questionnaire (PDQ). J Sex Med 2015;12:1072–1079.     

Concordance Between Patient and Physician Assessment of the Magnitude of Peyronie's Disease Curvature

IntroductionThe magnitude of penile deformity is a critically important factor in Peyronie's disease, as it is associated with increased difficulty in penetrative sexual intercourse and in turn with negative psychosocial consequences. Deformity magnitude also influences treatment choice when surgical correction is indicated.AimTo determine the concordance between patient and physician assessment of magnitude of penile curvature in men with Peyronie's disease.MethodsPatient assessment of curvature was obtained at initial interview. Physician assessment was performed using intracavernosal injection-assisted erection using a goniometer applied during excellent penile rigidity.Main Outcome MeasuresPatient and physician assessments of penile curvature.ResultsThe sample consisted of 192 men with a mean age of 54 ± 12 years old. Mean curvature on patient and physician assessment was 33 ± 17 and 36 ± 18 degrees, respectively. Only 49% of patients (94) correctly assessed their curvature, whereas 35% underestimated and 16% overestimated it.ConclusionsOnly half of PD patients accurately assess their penile curvature, with more than twice as many patients underestimating it than overestimating it. These data suggest that patient self-reporting of penile curvature should not be used as a clinical marker or end point in Peyronie's disease trials. Matsushita K, Stember DS, Nelson CJ, and Mulhall JP. Concordance between patient and physician assessment of the magnitude of Peyronie's disease curvature. J Sex Med 2014;11:205–210.     

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Use of Penile Extender Device in the Treatment of Penile Curvature as a Result of Peyronie's Disease. Results of a Phase II Prospective Study

IntroductionPilot experiences have suggested that tension forces exerted by a penile extender may reduce penile curvature as a result of Peyronie's disease.AimTo test this hypothesis in a Phase II study using a commonly marketed brand of penile extender.MethodsPeyronie's disease patients with a curvature not exceeding 50° with mild or no erectile dysfunction (ED) were eligible. Fifteen patients were required to test the efficacy of the device assuming an effect size of >0.8, consistent with an “important” reduction in penile curvature. Changes in penile length over baseline and erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) constituted secondary end points.Main Outcome MeasuresPatients were counselled on the use of the penile extender for at least 5 hours per day for 6 months. Photographic pictures of the erect penis and measurements were carried out at baseline, at 1, 3, 6, and 12 months (end of study). The IIEF-EF domain scores were administered at baseline and at the end of study. Treatment satisfaction was assessed at end of study using a nonvalidated institutional 5-item questionnaire.ResultsPenile curvature decreased from an average of 31° to 27° at 6 months without reaching the effect size (P = 0.056). Mean stretched and flaccid penile length increased by 1.3 and 0.83 cm, respectively at 6 months. Results were maintained at 12 months. Overall treatment results were subjectively scored as acceptable in spite of curvature improvements, which varied from “no change” to “mild improvement.”ConclusionsIn our study, the use of a penile extender device provided only minimal improvements in penile curvature but a reasonable level of patient satisfaction, probably attributable to increased penile length. The selection of patients with a stabilized disease, a penile curvature not exceeding 50°, and no severe ED may have led to outcomes underestimating the potential efficacy of the treatment. Gontero P, Di Marco M, Giubilei G, Bartoletti R, Pappagallo G, Tizzani A, and Mondaini N. Use of penile extender device in the treatment of penile curvature as a result of Peyronie's disease. Results of a phase II prospective study. J Sex Med 2009;6:558–566.     

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.     

Five-year follow-up of Peyronie's graft surgery: outcomes and patient satisfaction

IntroductionGraft surgery for Peyronie's disease (PD) is associated with significant long‐term risks.AimTo evaluate the clinical and functional outcomes of graft repairs with a minimum of 5‐year follow‐up.MethodsA retrospective review of database and third party telephone survey was undertaken in all men who underwent reconstructive graft procedures for PD between May 1999 and May 2005.Main Outcome MeasuresPatient demographics, International Index of Erectile Function (IIEF‐5) scores, and penile Doppler ultrasonography were performed preoperative. Follow‐up assessments included surgical outcomes and overall patient satisfactions.ResultsA total of 86 patients with an average age of 54.6 (34 to 73) years underwent Peyronie's graft repair. The average follow‐up was 98 (61 to 120) months. Twenty patients received dermal graft whereas 33 patients underwent Tutoplast graft and 33 patients had Stratasis small intestinal submucosa graft. Penile curvature greater than 60 degrees was more common in the Tutoplast and Stratasis groups. Twelve patients used phosphodiesterase type 5 inhibitors or intracavenous agents preoperatively. At the time of review, only 46 (53%) patients were able to be contacted and consented for telephone interview. Although 6 months of postoperative follow‐up showed excellent resolution, or significantly less, penile curvature, this figures decreased to 50% in dermal, 87% in Tutoplast, and 76% in Stratasis patients. Further penile length shortening was also reported on patient self‐assessment at the recent follow‐up. Worsening of IIEF‐5 scores were noted with the development of erectile dysfunction was more pronounced in the diabetic cohort (P < 0.01). The overall satisfaction on a 5‐point scale was 2.6 with more than 65% of patients dissatisfied with the outcomes of the Peyronie's graft surgery.ConclusionsThe recurrence of penile curvature, penile length loss, and the new‐onset of ED are not uncommon sequelae and are associated with a significant patient dissatisfaction rate when a 5‐year follow‐up is achieved. Chung E, Clendinning E, Lessard L, and Brock G. Five‐year follow‐up of Peyronie's graft surgery: Outcomes and patient satisfaction.     

High Patient Satisfaction of Inflatable Penile Prosthesis Insertion with Synchronous Penile Plication for Erectile Dysfunction and Peyronie's Disease

IntroductionTwenty to thirty percent of patients with Peyronie's disease (PD) have erectile dysfunction (ED) refractory to medical therapy and may benefit from a combined procedure addressing both conditions.AimThe aim of this study was to show the efficacy of inflatable penile prosthesis (IPP) insertion and synchronous penile plication for correcting penile curvature and ED in patients with PD.MethodsA retrospective review was performed of all patients who underwent IPP insertion with synchronous penile plication at our tertiary care center between 2010 and 2013. All patients received an intraoperative saline intracorporal injection to induce an artificial erection. After the tunica albuginea was exposed via a standard transverse scrotal incision over the proximal penile shaft, the incision was retracted distally and/or laterally as needed for plication suture placement. Plication sutures were placed in parallel opposite the angle of greatest curvature. The incision was returned proximally to the standard penoscrotal junction for IPP insertion. Demographic and surgical data were collected from the patients' medical records. Patient satisfaction was assessed postoperatively using a nonvalidated questionnaire.Main Outcome MeasuresThe focus of this study was surgical outcomes, both technical and patient-reported satisfaction.ResultsEighteen patients with a mean age of 63 years underwent IPP insertion with synchronous penile plication. Patients presented with dorsal (n = 11), lateral (n = 2), and biplanar curvature (n = 5). Mean preoperative curvature was 39 degrees (range 30–60) and was corrected on average to <5 degrees (range <5–12) using a median of four plication sutures (range 3–6). Among 15 patients completing a postoperative satisfaction survey at a mean of 11 months, all reported improvement in their overall condition and penile curvature; one with biplanar deformity reported minor residual curvature. None reported continued pain or required suture release.ConclusionsIPP insertion with synchronous penile plication for the correction of ED and PD is effective and results in high patient satisfaction. Chung PH, Scott JF, and Morey AF. High patient satisfaction of inflatable penile prosthesis insertion with synchronous penile plication for erectile dysfunction and Peyronie's disease. J Sex Med 2014;11:1593–1598.     

Multicenter Experience Using Collagen Fleece for Plaque Incision With Grafting to Correct Residual Curvature at the Time of Inflatable Penile Prosthesis Placement in Patients With Peyronie's Disease

BackgroundAdjuvant maneuvers are often necessary to correct residual curvature during inflatable penile prosthesis (IPP) placement in patients with Peyronie's disease (PD).AimWe present our multicenter experience using collagen fleece as graft material for plaque incision and grafting (PIG) during IPP placement in patients with moderate to severe PD.MethodsWe retrospectively reviewed 51 patients with IPP from 3 sites who underwent PIG with Tachosil (Baxter, IL) collagen fleece. Coloplast (Minneapolis, MN) IPP devices were used. Factors associated with residual curvature, revision, and patient satisfaction were performed using chi-squared analysis.OutcomesWe evaluated postoperative outcomes including factors associated with residual curvature, revision, and patient satisfaction.ResultsThe mean compound curvature was 69.6°. The mean follow-up was 10.6 (range 1–38) months. All patients reported erections sufficient for penetrative intercourse at the last follow-up. Residual curvature <15° was noted in 6 of 51 (12%) patients. 3 patients required device revision. 2 patients experienced temporary glanular paresthesia, and no patients experienced device infection.Clinical ImplicationsIn our multicenter study, patients experienced substantial curve correction with minimal complications, and in the few patients who had persistent mild curvature, severe preoperative curvature (>60°) was found to be the only risk factor.Strengths & LimitationsOur study represents the largest series of patients coming from multiple centers undergoing surgical correction of PD with IPP and collagen fleece grafting. Limitations of this study include the retrospective study design, lack of a comparison group, and modest follow-up.ConclusionPIG using collagen fleece is a safe and effective means of correcting residual curvature after IPP placement in patients with moderate to severe PD.Hatzichristodoulou G, Yang DY, Ring JD, et al. Multicenter Experience Using Collagen Fleece for Plaque Incision With Grafting to Correct Residual Curvature at the Time of Inflatable Penile Prosthesis Placement in Patients With Peyronie's Disease. J Sex Med 2020;17:1168–1174.     

Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach

IntroductionThe conception of collagenase Clostridium histolyticum (CCH) as treatment for Peyronie's disease (PD) was a vital first step in providing a nonsurgical, minimally invasive FDA-approved treatment for men with PD.AimTo review the origins, clinical research history, and ultimately FDA approval of collagenase as PD treatment.MethodsA PubMed search using (Peyronie's or Peyronie) AND collagenase, and limited to clinical research studies, returned nine papers that were examined in the current review.ResultsCollagenase as a PD treatment arose in response to a lack of effective nonsurgical treatments and the incomplete understanding of underlying PD etiology. Awareness of dense collagen in PD scarring and parallel initial exploration of collagenase to treat herniated lumbar discs coincided with and inspired laboratory-based investigation of collagenase effects on excised PD plaque tissue. The foundational conceptual work and the critical development of purified injectable collagenase allowed the pursuit of clinical studies. Progression of clinical studies into large-scale robust trials culminated in two important outcomes: development of the first validated, PD-specific measure of psychosexual function, the Peyronie's Disease Questionnaire, and the first FDA-approved treatment for PD.ConclusionsCollagenase therapy began as an attempt to modify the structure of PD-related tunica albuginea scarring, despite the lack of a fundamental understanding of the scar's origin. If we wish to advance PD treatment beyond this first effective step, the future needs to bring us full circle to the starting point: We need a greater understanding of the control of collagen deposition and wound healing in men with PD. Gelbard MK, Chagan L, and Tursi JP. Collagenase Clostridium histolyticum for the treatment of Peyronie's disease: The development of this novel pharmacologic approach. J Sex Med 2015;12:1481–1489.     

Surgical Reconstruction of Penile Curvature due to Peyronie's Disease by Plaque Incision and Buccal Mucosa Graft

Background/aimWe aimed to evaluate the effectiveness and safety of penile plaque incision and buccal mucosa grafting in patients with stable-phase Peyronie's disease (PD).MethodsThis was a prospective evaluation of patients with stable-phase PD who were treated by plaque incision and buccal mucosa grafting. Preoperative evaluation included International Index of Erectile Function Questionnaire (IIEF-5), measurement of erect penile length, and penile Doppler ultrasound during prostaglandin-induced erection. At 3- and 24-month follow-up visits, penile length and residual curvature were measured along with penile Doppler ultrasound and IIEF5 questionnaires. Patient and sexual partner satisfaction were also assessed at 24-month-visit.ResultsThe study was completed with 20 patients (mean age 46.5 ± 9.9 years). Dorsal curvature was the most frequent site of curvature (45%). The median curvature at preoperative evaluation was 45°(range 40-90°). The postoperative median curvatures were 5°(5-10, IQR) and 7°(5-10, IQR) at 3- and 24-month postoperatively, respectively. Success rate was 95% at 3-month and 90% at 24-month. There was no significant penile shortening. The mean IIEF-5 score was 17.5 ± 2.2 at preoperative evaluation. The median IIEF-5 scores were calculated as 20.1 ± 2.2 and 21.3 ± 2.2 at 3-month and 24-month visits, respectively (p<0.0001). Compared with baseline IIEF-5 score, both postoperative IIEF-5 scores were significantly higher. There was no de novo erectile dysfunction. There were no serious complications during and after the surgery. Ten percent of patients were poorly satisfied with the results of the surgery.ConclusionCorporoplasty with buccal mucosa graft led to excellent structural and functional results and patient satisfaction.Ainayev Y, Zhanbyrbekuly U, Gaipov A, et al. Surgical Reconstruction of Penile Curvature due to Peyronie's Disease by Plaque Incision and Buccal Mucosa Graft. J Sex Med 2021;18:1308–1316.