Single Intrasphincteric Injection Of Autologous Adipose-derived Stem Cells To Treat Stress Urinary Incontinence After Radical Prostatectomy: A Pilot Study

Moussa M1, Dabboucy B1, Papatsoris A1, Moussa Y1, Fares Y1, Dellis A1, Issa H1, Bailly H1, Abou Chakra M1

Research Type

Clinical

Abstract Category

Male Stress Urinary Incontinence (Post Prostatectomy Incontinence)

Abstract 2
Best Urology
Scientific Podium Session 1
Thursday 8th September 2022
09:20 - 09:35
Hall D
Incontinence Clinical Trial Stress Urinary Incontinence Surgery
1. Lebanese University, Stem Cell Center, Beirut, Lebanon
Online
Presenter
M

Mohamad Moussa

Links

Abstract

Hypothesis / aims of study
Stress urinary incontinence (SUI) post radical prostatectomy (RP) is reported in up to one-third of patients. Depending on the degree of leakage and associated bother, many patients will seek definitive surgical management. Options for surgical management generally include a male sling (MS) or artificial urinary sphincter(AUS)[1]. In a systemic review including analysis of data of 4022 patients, the efficacy (0-1 safety pads) was on average 65.7% for AUS and 48.2% for MS. The overall complication rate of the 2 techniques was more than 10% [2]. Stem cell therapy is a promising treatment for many urological conditions. Intrasphincteric injections of Adipose-derived stem cells (ADSCs) may have a role in treating SUI post RP. The objective of this study was to assess the safety and efficacy of intrasphincteric ADSC injections to treat SUI post RP
Study design, materials and methods
Between January 2019 and December 2021, we performed a prospective trial that enrolled male patients with SUI post RP. A total of 10 patients were randomized into 1 of 2 groups: treatment group (received a single injection into the urethral rhabdosphincter 10ml of ADSC solution), or placebo group (single injection into the urethral rhabdosphincter of 10ml of normal saline). ADSCs were injected using a template showing 8 injections (1.25 ml/injection) throughout the rhabdosphincter, at 12,6,3,9,2,10,5, and 7 o’clock positions. Injections were delivered at a depth of 5 mm with a rigid scope under general anesthesia using a bladder injection needle 22Gauge  (tip length 4mm, working length 35cm). ADSCs solution was reconstituted in 5 ml of sterile saline. Liposuction was performed from the treatment group to isolate ADSCs. Briefly, the lipoaspirate was digested with collagenase, at 37 °C. Then it was washed 3 times with cold phosphate-buffered saline (PBS). The Stromal vascular fraction was plated into a culture flask. The medium was replaced every 3 days and cultured in expansion. The cells are used after confluence in the first passage. 
Inclusion criteria were: patients with an SUI for > 18 months after surgery, localized low to intermediate-risk prostate cancer before surgery, have no biochemical recurrence at study enrollment, the patient had no adjuvant chemotherapy or radiotherapy, all patients had pelvic floor training for > 6 months. All patients had office cystoscopy before entering the study to exclude bladder neck contracture or urethral stenosis.
Exclusion criteria were: patients taking anticholinergic medications for overactive bladder symptoms or taking a diuretic for heart failure, patients with urinary tract infection, patients with any neurologic disease that may affect bladder function.
Eligible participants were randomly assigned to one of the 2 groups by a computer-generated lottery. Both the urologists and the patients were blinded to the treatment assignments.
The amount of incontinence was evaluated with a 24-h pad weight test. This test was noted in each evaluation period ( baseline, 1, 3, 6, 12, and 18  months). Patients were allowed to use as many pads as they deemed necessary and were provided sealable bags labeled day 1, 2, and 3. They were asked to store their pads in the provided sealed bag in the refrigerator to minimize evaporation. The patient brings all pads to each clinical visit. Each soiled pad was weighed using a calibrated scale. The mean of 24-hour pad weight noted during the 3 days in each patient was calculated at baseline and during each clinical visit. Quality-of-life survey (International Consultation on Incontinence Questionnaire- Short Form (ICIQ-UI SF) was collected before therapy and during the follow-up visit. 
Incontinence has been categorized into three categories based on the gram (g) weight of urinary loss–mild SUI, or <100g/24 hours, moderate SUI, or 100–400g/24 hours, and high-grade, or >400g/24 hours to help classify the degree of incontinence [3].
The primary outcomes of our study were the change from baseline in the mean of the 24-h pad weight test. The secondary outcomes were the change from baseline in the mean of ICIQ-UI SF score. Safety assessments included any reported adverse events. 
The study was approved by our Institutional Review Board (N.05/2019). This trial was registered in the UMIN clinical trial registry (UMIN000047336). Written informed consent was taken by all the patients to participate in the study.
Results
The mean follow-up period was 22 months in the treatment group and 23 months in the placebo group. A total of 10 patients were included in the study. Most of the patients in both groups had ages between 60 and 70 years, had SUI  20 to 24 months post-surgery (Table 1).
A significant reduction of the mean 24-h pad weight test in g was noted in the treatment group. In this group, the mean 24-h pad weight decreased from 320 g (moderate SUI) at baseline to 70 g (mild SUI). In the placebo group, the mean 24-h pad weight test in g was not significantly changed (remain in the moderate SUI category). Significant improvements from baseline were noted for the mean ICIQ-UI SF score in the treatment group. In this group, the mean ICIQ-UI SF score decreases significantly from 19 at baseline to 8 at the end of therapy. In the placebo group, the mean ICIQ-UI SF score remains the same till the end of the study. The outcomes of the study are summarized in table 2.

There were no serious adverse events reported in the treatment or placebo group
Interpretation of results
Our study report that intrasphincteric ADSCs could improve SUI  progressively during the 18 months follow-up period, as determined by a decrease in 24-h pad weight test, and improved quality of life evaluated by a validated quality of life questionnaire.
We used the ICIQ-SF for the quality-of-life analysis and were able to prove quality-of-life improvement during the follow-up period in the treatment group
The main limitation of our study is the small sample size and relatively short-term follow-up
Concluding message
Findings from this study provide preliminary evidence in support of the safety and potential clinical utility of intrasphincteric ADSCs injections for the treatment of SUI post RP
Figure 1 Table 1. Patient demographic and other baseline characteristics
Figure 2 Table 2. The difference from Baseline in treatment and Placebo groups for results of mean of 24-h pad weight test and ICIQ-UI SF score
References
  1. Malik RD, Cohn JA, Fedunok PA, Chung DE, Bales GT. Assessing variability of the 24-hour pad weight test in men with post-prostatectomy incontinence. Int Braz J Urol. 2016;42(2):327-33
  2. Crivellaro S, Morlacco A, Bodo G, Agro' EF, Gozzi C, Pistolesi D, Del Popolo G, Ficarra V. Systematic review of surgical treatment of post radical prostatectomy stress urinary incontinence. Neurourol Urodyn. 2016;35(8):875-881
  3. Kumar A, Litt ER, Ballert KN, Nitti VW. Artificial urinary sphincter versus male sling for post-prostatectomy incontinence--what do patients choose? J Urol. 2009;181(3):1231-5
Disclosures
Funding None Clinical Trial Yes Registration Number UMIN Clinical Trials Registry (UMIN-CTR); (UMIN000047336) RCT Yes Subjects Human Ethics Committee Ethical committee of Al Zahraa Hospital, Beirut, Lebanon Helsinki Yes Informed Consent Yes
Citation

Continence 2S2 (2022) 100192
DOI: 10.1016/j.cont.2022.100192

28/04/2024 19:26:29