Hypothesis / aims of study
Stress urinary incontinence (SUI) commonly occurs in women after delivery, neurogenic lower urinary tract dysfunction, and also in men after radical prostatectomy. If conservative treatment such as pelvic floor exercise or medical treatment fails, surgical intervention to restore urethral competence by suburethral sling, urethral bulking agent injection, or artificial sphincter implantation are usually necessary for patients with moderate to severe urinary incontinence. However, patients with mild urinary incontinence might not accept the active surgical management. Currently, there is no simple way to resume a tight urethral sphincter and urinary continence. Autologous platelet-rich plasma (PRP) is growing in popularity as a therapy to augment wound healing, speed the recovery from muscle and joint injuries, and enhance recovery after surgical repair. PRP is extremely rich in growth factors and cytokines, which regulate tissue reconstruction and has been studied extensively among trauma patients and trauma experimental models. It is possible that the deficient urethral sphincter might regain its sphincter innervation and striated muscle cells through repeat PRP injections. This study attempts to use autologous PRP in treatment of SUI due to ISD which is refractory to currently available medical treatment or failure after previous surgical therapy.
Study design, materials and methods
A total of 20 patients with SUI due to ISD who have failed conventional treatments or failure after previous surgical therapy for at least 12 months were enrolled in this study. A diagnosis of ISD has been established based on characteristic symptoms and video urodynamic study. All patients have mild to moderate urinary incontinence and pad protection is necessary. The patients received urethral sphincter injection of 5 mL PRP with platelets concentration 5 times of the peripheral blood (extracted from 50ml of patient’s own whole blood) under intravenous general anesthesia in the operation room. The procedure will repeat every one month for a total of four treatments. Primary end-point is the change of the objective assessment of urinary incontinence severity by visual analog scale (VAS, from 0-10, indicating severe urinary incontinence to no incontinence) from baseline to 3 months after the fourth PRP treatment day. Secondary end-points include: (1) Global response assessment (GRA) of satisfaction by the patient (categorized into -3, -2, -1, 0, 1, 2, 3, indicating markedly worse to markedly improved) at 6 months after the treatment day. An improvement of GRA by 2 scales is considered effective. (2) Net change of daily pad use. (3) Net change of the following parameters from baseline to 3 and 6 months after the treatment day: functional bladder capacity (FBC), voiding frequency at daytime and voiding frequency at night time as record in 3-day voiding diary. (4) Net changes of the maximum flow rate (Qmax), voided volume (Vol) and post-void residual (PVR) volume from baseline to 3 and 6 months after the first treatment day. (5) Changes of abdominal leak point pressure (ALPP), maximal urethral closure pressure (MUCP) and functional profile length (FPL) from baseline to 3 and 6 months after the first treatment day. (6) IIQ-7 questionnaire to assess the impact of urinary incontinence on the quality of life from baseline to 3 and 6 months after the first treatment day.
The patients included 15 men and 5 women who had SUI after radical prostatectomy (n=14), neurogenic LUTD (n=4) and SUI after prior anti-incontinence surgery (n=2). After 3-4 PRP injections, 14 (70%) patients had improvement of SUI severity. Among them 9 (45%) achieved a satisfactory result with wearing less than a pad per day and 5 (25%) had marked improvement with fewer pad compared with baseline need. The severity of SUI improved after the first PRP injection and further improved after subsequent treatments. The VAS of SUI was 3.27 ± 0.41, 4.67 ± 0.49, 5.40 ± 0.63, 5.87 ± 0.67, and 6.27 ± 0.72 at baseline, 1 month after 1st, 1 month after 2nd, 1 month after 3rd, and 1 month after 4th PRP injection, respectively. Two patients who failed PRP treatments had severe ISD due to neurogenic urethral sphincter deficiency. Four patients with postprostatectomy SUI were older than 80 years old. Mild hematuria and micturition pain were noted in 3 patients but resolved after medical treatment. There were no adverse events such as dysuria, urinary tract infection, or urinary retention.
Interpretation of results
This study reveals that PRP is effective and safe in improving SUI in patients with ISD. Neurogenic ISD fare less than non-neurogenic ISD, suggesting a less regenerative effect of PRP on these neurogenic patients. Patients who are older than 80 years old might not benefit from PRP injections because the urethral sphincter is much weaker than that in younger patients. PRP can increase urethral resistance and decrease the SUI severity. In patients with mild to moderate ISD due to radical prostatectomy or detrusor underactivity PRP can provide a second line treatment if conservative treatment fails.