53 Low-intensity Extracorporeal Shockwave Therapy as an Adjunct to Xiaflex® in the Treatment of Peyronie's Disease

Abstract

Introduction Low-intensity extracorporeal shockwave therapy (Li-ESWT) may have physiologic effects including neo-angiogenesis, upregulation of vasoactive endothelial growth factors, nerve recovery, reduction of fibrotic changes, cavernosal tissue remodeling, and reduction in sympathetic tone. Collagenase clostridium histolyticum (CCH) is the only US FDA-approved drug for the non-surgical treatment of Peyronie's disease (PD). Treatment is intended to be completed in conjunction with penile traction therapy, but studies have demonstrated poor patient compliance. New adjunct therapies that have synergistic effects when used in combination with CCH are desirable but have not been explored. Objective To study if Li-ESWT has additive, synergistic, or no effect when used in combination with CCH to treat PD-associated fibrosis and PD-associated erectile dysfunction. Methods 40 adult male Sprague-Dawley rats were divided evenly into five groups: sham (S), control (T), CCH only (XT), low setting Li-ESWT and CCH (XTL), and CCH and high setting Li-ESWT (XTH). Normal saline was injected sub-tunical in the sham group. Transforming growth factor beta-1 (TGF-B1) was injected into the tunica albuginea of the remaining groups to induce Peyronies-like fibrosis. After 4 weeks of TGF-B1 induction, CCH was injected in all three groups over two injections separated by 48 hours, and then treatment with Li-ESWT (UroGold™ 100) was initiated. Treatment was delivered biweekly for 3 weeks (6 total sessions). Device settings were 600 shocks at 3 Hz, at level 6 (0.093 mJ/mm2) for the XTL group and at level 12 (0.125 mJ/mm2) for the XTH group. After 10 weeks, erectile function was measured by ratio of intracavernosal pressure (ICP) to mean arterial pressure (MAP). Histological analysis by H&E, Trichome stain, and Western blot analysis of Collagen I (COL1A1), III (COL3A1), and alpha-smooth muscle actin (a-SMA) were also performed. Results There was no significant difference found in erectile function as measured by ICP/MAP between PD model and treatment groups (P > 0.05). Histological comparison showed no significant reduction of fibrosis when Li-ESWT was added to CCH, despite intensity, on microscopic examination. On Western blot analysis, there was a reduction of ∼500% in COL1A1 expression when the XT group was compared to the T group. While there was no significant change of COL1A1 between the XT group and the XTL group, there was found to be a decrease of ∼500% expression when the XT group was compared to the XTH group. Expression of COL3A1 in the treatment groups XTL and XTH was comparable to that of the XT group. There was no observable trend in a-SMA expression. Conclusions Different adjunct treatments to CCH need to be explored to augment the effect of the only approved non-surgical treatment for PD. Decreased COL1A1 expression seen in the XTH group, but not XTL, relative to the T group may suggest an energy-dependent effect to decrease fibrosis. Li-ESWT was hypothesized to be a promising candidate, but we have failed to show substantial benefit in our proposed setting. Disclosure Yes, this is sponsored by industry/sponsor: Sexual Medicine Society of North America Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals