Savage, J

Abstract Introduction Since FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. We therefore sought to compare key outcomes between the two therapies. Objective To compare the satisfaction and adverse event profiles between surgery and CCH injections for the treatment of PD. Methods A randomized, controlled trial is ongoing. Participants were randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil (CCH) or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD (Surgery). Objective, standardized, and non-standardized assessments were obtained at baseline and 3, 6, 12, 24, 36, 48, and 60 months post-treatment. Key outcomes included differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Results A total of 40 men were randomized with 24-month data available in 29. Mean age was 54.7 years, PD duration 37.4 months (mo), composite curvature 73.1 degrees (deg), and penile length 12.7 cm. All baseline variables were similar between cohorts. Regarding primary outcomes, at 24-months post-treatment, CCH men were more likely to report being very satisfied with treatment (62% vs 25%, p < 0.05). For secondary outcomes, only questionnaire data were captured at two years without objective measurements obtained. No differences were noted between groups regarding subscales of the IIEF, PDQ, Beck’s Depression Inventory, or SEP-2, however CCH men had better SEP-3 positive responses (62% vs 19%, p = 0.02), indicating improved ability to maintain erections sufficient for intercourse. Surgery men reported higher subjective rates of length loss compared to CCH (81% vs 15%, p < 0.001) and curvature recurrence (56% vs 8%, p < 0.01), but similar rates with changes in sensation, indentation/hourglass, and erectile function. Both groups indicated similar willingness to undergo the therapy again. Interestingly, at 2-years, the majority of men in the Surgery arm said that their initial preference for treatment was surgery (56%), which decreased from a peak 86% at 1-year. However, in reviewing baseline information, 72% of Surgery men actually preferred CCH at study onset, highlighting a significant recall bias towards whatever treatment one actually ended up receiving. Conclusions Preliminary data suggests that when compared to surgery at 24-months, CCH men were more likely to be very satisfied with therapy, have greater subjective length improvements and lower curvature recurrence rates. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: PathRight Medical.

ABSTRACT Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. Specifically, investigators have compared relative utilization, costs, and outcomes with varying conclusions. Objective To compare various objective and subjective outcome measures between men undergoing CCH or surgery for PD. Methods A randomized, controlled trial (NCT04786106) is ongoing at ***. Participants are randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD. Objective, standardized (International Index of Erectile Function [IIEF] and Peyronie's Disease Questionnaire [PDQ]), and non-standardized assessments are obtained at baseline, and post-treatment at 3, 6, 12, 24, 36, 48, and 60 months. Key outcomes include differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Curvature is measured in two planes and summed to provide a composite curvature. Penile length is measured from pubic symphysis to corona. All therapies were stopped prior to the 3-month time point (i.e. traction and sildenafil). Results A total of 32 men have been randomized to date (CCH=17, surgery=15), with 3-month data available on 8 men (CCH=4, surgery=4). Mean age at enrollment was 55.8 years (SD 14.4), PD duration 38 months (SD 49.5), curvature 74.1 degrees (SD 20.9), and penile length 12.5 cm (SD 1.5). All baseline variables were statistically similar between cohorts. Regarding the primary outcome, at 3 months post-treatment, CCH men reported higher overall satisfaction (not statistically significant; 50% very satisfied, 50% somewhat satisfied; surgery 100% somewhat satisfied, p=0.06). For secondary outcomes at 3 months, the median differences between CCH and surgery respectively were: IIEF-EFD (+4 vs +4, p=1.0), PDQ-physical (-10 vs -6.5, p=0.14, note: lower is better for PDQ scales), PDQ-pain (-12 vs 0.5, p=0.77), PDQ-bother (-9 vs -8, p=0.77), length change (+0.8 vs 0 cm, p=0.29), curvature absolute change (-22.5 vs -80 degrees, p=0.11), and curvature percentage improvement (41% vs 85%, p=0.11). An equal number of CCH and surgery men felt that treatment improved sexual function (75%) and their ability to have sex (100%) and were subjectively happy with their curvature (50%). Men in the surgery arm were more likely to report (note that some are not statistically significant) subjectively worsened erectile function (50% vs 0%, p=0.15), shorter penile length (75% vs 0%, p=0.02), lower satisfaction with penile length (50% satisfied vs 75%, p=0.46), improved hourglass (33% vs 0%, p=0.42), and were less likely to report that they would repeat treatment without reservation (50% vs 75%, p=0.11). When asked which treatment they would pick if they could start again, 100% of CCH men reported CCH and/or traction, while 50% of surgery men indicated surgery, 25% CCH, and 25% other (p<0.05). Conclusions The current data are too preliminary to draw any viable conclusions on differences between CCH and surgery for PD. Disclosure Work supported by industry: yes, by Endo Pharmaceutical.