(P13) penile shear wave elastography may predict the outcome of intra-cavernosal injection by Onabotulinumtoxin a (Botox) in management of men with erectile dysfunction and phosphodiesterase-5- 5 inhibitors non-responders

Abstract Background Erectile dysfunction (ED) is defined as failure to attain or maintain an erection for satisfactory sexual performance. Phosphodiesterase-5 inhibitors (PDE-5i) are considered a first-line treatment option for the management of (ED). In PDE-5i non-responders, different treatment modalities are available, including prostaglandin E1 (PGE1) intra-cavernosal injections (ICI), low intensity shockwave therapy and penile prosthesis implantation. Botulinum Neurotoxin (BoNT) is produced by anaerobic bacteria termed Clostridium botulinum, with seven different serotypes (BoNT A-G). BoNT-A is the most common form used clinically. Prolonged reduction of cavernosal smooth muscle tone may explain the observed clinical improvement after BoNT-A injection in ED patients. BoNT-A facilitates smooth muscle relaxation by inhibiting presynaptic release of pro-contractile norepinephrine from adrenergic neurons. Furthermore, BoNT-A inhibits acetylcholine release from cholinergic neurons, which inhibits nitric oxide (NO) synthase. Elastography is an emerging class of medical imaging that evaluates tissue stiffness. Tissue stiffness value (TSV) measured by Shear wave elastography (SWE) was found to be significantly higher in ED patients in comparison with controls, reflecting a different number and tone of cavernosal smooth muscles, and content of collagen fibres in corpora cavernosa. This study aimed to assess (SWE) ability to predict the outcome of BoNT-A in the management of men with ED and PDE-5i non-responders. Methods This prospective study was conducted between May 2023 and March 2024 in Cairo University Hospital and comprised twenty men presenting with ED and PDE-5i non-responders. It was registered under protocol record NCT06044883 and received approval by the local research ethical committee under code MS-191-2023. Each patient received a total of 100 U of Onabotulinumtoxin-A (Botox, Allergan Pharmaceuticals, NJ, USA) diluted in 2 ml of normal saline. Patients were instructed to resume sexual activity after one week using the maximum tolerable dose of PDE5-i. The International Index of Erectile Function (IIEF-5), Sexual Encounter Profile questions 2 and 3 (SEP-2 and SEP-3), and Erection Hardness Score (EHS), penile hemodynamic parameters using duplex ultrasound and mean tissue stiffness value (TSV) using (SWE) were measured before and after BoNT-A injection by 6 and 12 weeks. Ultrasonographic, duplex and elastography measurements were done using Aplio 500 (Toshiba Medical Systems, Japan) with a linear probe (7.5 − 13 MHz). Penile duplex ultrasound was done to evaluate hemodynamic parameters: peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI). Induced erection during penile duplex and (SWE) was done using 20 μg (PGE-1) (Alfaprostin, Rotabiogen Pharmaceuticals, Egypt). (SWE) Measurements were taken in the longitudinal plane at the mid-third of the penis. Three regions of interest (ROI) circle area elastography measurements were taken for each corpora cavernosa, and the arithmetic mean of the six readings was calculated. Mean (TSV) values were measured in kilo Pascal (kPa), with a higher value referring to a greater stiffness. Results After BoNT-A injection, 7/20 (35%) regained an erection sufficient for vaginal penetration by using maximum tolerable PDE-5i doses. A mean TSV value in the flaccid state of >12.7 kPa was found predictive of failure of regaining erection after BoNT-A injection with the aid of the maximum tolerable dose of PDE-5i (sensitivity = 100%, specificity = 54%, AUC = 0.86, (p 0.014). In contrast, mean TSV in PGE1 induced erection was not a significant predictor of regaining PDE-5i induced erection after BoNT-A injection (AUC = 0.53, p = 0.8). Conclusion Penile SWE could be used for evaluation of cavernosal tissue integrity and patient selection before BoNT-A injection in men with advanced ED and PDE-5i non-responders. This finding could be applied to avoid unnecessary BoNT-A injections in men with terminal forms of ED and less likely to benefit from this treatment modality.