**4. Treatment options**

#### **4.1 Conservative and pharmacological treatments**

After RP, improvements in continence status will evolve from the early postoperative period until the end of the first year [8, 58]. Before proceeding to more invasive treatments, conservative management should be evaluated, and patients should be monitored regularly to determine the degree of improvement [16]. The most common conservative treatments are lifestyle interventions, physiotherapy (PFMT) with or without biofeedback or electrical stimulation, and pharmacotherapy.

Lifestyle interventions include time voiding or double voiding, fluid restriction, smoking cessation, and reducing bladder irritants (caffeine, alcohol, hot spices) [16, 41].

PFMT consists of a program of repeated voluntary pelvic floor muscle contractions to improve the closure mechanism due to the levator ani muscle [59, 60]. According to the current European Association of Urology (EAU) guidelines, PFMT should be offered to all patients undergoing RP to speed up postoperative continence recovery [41]. Debate on combining PFMT with additional biofeedback training or electrical stimulation is ongoing. Current evidence supporting PFMT with or without biofeedback is conflicting; some randomized trials demonstrated improved continence thanks to biofeedback therapy [61], and others indicated no benefit [62]. Based on 7th International Consultation on Incontinence (ICI), to achieve a significant improvement, PFMT should be performed for at least 3 months from RP and should be offered for periods of up to 6–12 months [63]. Evidence suggests that electrical stimulation may accelerate urinary continence recovery, but no long-term benefit has been demonstrated at 6 months or more after surgery [64].

Regarding pharmacologic treatments, no approved drugs yet exist. Antimuscarinics, phosphodiesterase inhibitors, and alpha-adrenergic agonists have been proposed as potential therapies for PPUI, especially in patients with OAB symptoms, demonstrating unexciting results [65].

Duloxetine, a serotonin-noradrenaline reuptake inhibitor, is the only available medical treatment that showed clinical efficacy for mild-to-moderate PPUI, increasing the neural tone of the urethral sphincter to prevent incontinent episodes [66, 67]. It has been approved for female stress urinary incontinence in some countries, but there is evidence that it reduces SUI-related symptoms in males [68, 69]. Gastrointestinal and central nervous side effects are common, leading to 15–31% of withdrawal [70]. These side effects are usually limited to the initial phase, and the use of duloxetine can be efficacious with persistence [71]. Some authors showed that duloxetine has synergistic effects when combined with PFMT [72]. However, clinical evidence supporting their routine use is weak. These two treatments seem to improve early continence recovery moderately, but neither significantly improves long-term urinary continence [73]. Recent results from a randomized clinical trial by Sanchez-Salas et al. demonstrated that PFMT and duloxetine do not improve urinary continence recovery, may have a negative impact on quality of life, and should not be routinely recommended to patients after RP [30].

In the case of refractory PPUI, more invasive and effective options are recommended.

#### **4.2 Surgical treatments**

If conservative therapy fails, surgical treatment options should be offered. Invasive treatment options include peri-urethral balloons, bulking agents, artificial urinary sphincters (AUS), and male slings.

AUS and perineal slings are the most used surgical treatment options. European guidelines recommend the AUS implantation for patients with moderate-to-severe PPUI after unsuccessful conservative treatment. Conversely, for mild-to-moderate PPUI, fixed perineal slings are recommended [74]. As a result, moderate urinary incontinence is in a "grey area" in which both AUS and slings are indicated, despite growing evidence that AUS significantly outperforms fixed slings in men with moderate PPUI [75].

Peri-urethral balloons can be considered a salvage therapy for mild, persistent, or recurrent PPUI after implantation of a fixed male sling [74].

#### *4.2.1 Artificial urinary sphincter*

The AUS was conceptualized and created by F. Brantley Scott in 1973 [76]. The original AMS 721 model has undergone several modifications and enhancements, leading to the current model AMS 800® (Boston Scientific, Boston, MA, USA), which is the currently established standard for managing moderate to severe PPUI [77]. The AUS comprises a urethral cuff, a pressure-regulating balloon (PRB), and a pump. It is a hydraulic, mechanical device functioning through a circumferential compression of the urethra. The PRB and the cuff come, with different pressure ranges and sizes, respectively, to adapt the device to the patient's characteristics.

After five decades since its introduction, a considerable number of cohort studies have demonstrated the efficacy and reliability of AUS in terms of continence and quality-of-life improvement [77]. However, significant limitations to AUS use include the device's mechanical nature, which necessitates adequate manual dexterity and cognition, the persistent need for some pad use in many patients, the worries over potential complications, the need for reoperation due to mechanical failure in about a third of patients, and costs. Consequently, patients should be really motivated for the implantation and informed about the risk of future reoperations.

At our institution, patient preparation is performed following an internal protocol. Antiseptic washing is performed the day before surgery, and trichotomy is done just before surgery. Patients are placed in a high lithotomy position, and chlorhexidine gluconate abdominal and perineal scrub (10 min) is performed. An abdominal-perineal dual-surgical approach is usually used. We implemented a standardized protocol for asepsis to avoid infection, including minimization of operating room traffic, dual single-shot antibiotic prophylaxis (cephazolin and gentamicin), minimum air exposure of the device component, use of double gloves by the members of the surgical team with frequent gloves changes, as well as rinsing of the operative field and PRB with antibiotic solution, use of medicated drapes to isolate skin, meticulous hemostasis, and minimization of tissue dissection. A 12 Fr transurethral catheter is used. In cases of bladder neck contracture, patients are preferentially treated by adopting a two-stage approach with an endoscopic incision performed before the AUS implantation. We usually transpose the cuff tube at the abdominal level and suture the perineum at this point of the procedure to minimize air exposure. The PRB (61–70 cmH2O) is placed intraperitoneally through a McBurney incision, and the pump is implanted in the scrotum. At the end of the procedure, the system is cycled twice, and the pump is deactivated. Skin incisions are approximated with adsorbable running intradermal sutures. The bladder catheter is removed on postoperative day two. Patients are discharged on day three, and the urinary sphincter is activated 6 weeks later [78].

PRB placement has evolved. Some surgeons place it in the space of Retzius. This location has rarely been associated with serious complications, given its proximity to the bowel and bladder. Other authors suggested an alternative ectopic PRB placement via a counter incision in the anterior abdominal wall [79]. Balloon herniation, palpability, and pain represent a possible bothersome complication of the aforementioned locations, thereby, we utilize a deeper pelvic location (intraperitoneally) through a suprainguinal incision.

In clinical practice, one may encounter situations (previous radiotherapy, previous UI surgery, etc.) requiring a different surgical approach.

The bulbar urethra at the level of the bifurcation of the corporal bodies is the most frequently used site for AUS cuff implantation [80]. A distal single or double cuff placement is commonly required in patients undergoing AUS reimplantation following urethral erosion or in those with urethral atrophy at the original cuff site [81]. In cases of compromised urethra due to prior AUS placement, previous radiation therapy, or urethral surgery, the AUS cuff may be placed through a transcorporal approach that protects the posterior wall of the urethra during dissection to decrease the risk of urethral lesions or erosion [82]. The risk of impaired erectile function due to disruption of the tunica albuginea of the corporal bodies is the major drawback of the transcorporal approach that limits its widespread use [83].

The AMS 800 remains the gold standard treatment for PPUI, offering a very satisfactory and predictable continence rate and high patient satisfaction.

Definitions of continence based on pad use are heterogenous in the literature; however, in AUS publications, the "social continence, defined as the use of, at maximum, one pad per day, is the most used quantitative functional outcome." Van der Aa et al. reported a social continence rate of 79.0% (60.9–100%) [77].

However, AUS implantation is associated with a likely underreported risk of intraoperative urethral lesions and postoperative urethral erosions [77]. The data about infection and erosion rates after AUS placement are inconsistent, with most papers not reporting the erosion and the infection rates separately, counting them as a composite outcome. In a pooled analysis [77] of 12 studies, the mean infection plus erosion rate was 8.5% (3.3–27.8%).

Based on the bi-layered structure with multiple sublayers of the tunica albuginea of the corpora cavernosa, we assessed an alternative "*transalbugineal*" AUS implantation technique intending to decrease perioperative morbidity while preserving the integrity of the corpora cavernosa [78]. After identifying and splitting the bulbospongiosus muscle, the corpus spongiosum is gently exposed in its anterolateral aspect. Buck's fascia is incised bilaterally, and the posterior dissection is performed starting 5 mm off the bulbar urethra on both sides, entering the multilayered structure of the tunica albuginea of the corpora cavernosa, thus leaving its external layer attached to the posterior aspect of the urethra. The main aim of our modified technique was to reduce the risk of intraoperative urethral injuries and the risk of postoperative urethral erosion (and consequent infection) due to shallow dissection, without compromising sexual function in potent patients. Our refined implantation technique was demonstrated to be effective, safe, and reproducible, with continence rates similar to those achieved using a conventional approach.

Further potential complications consist of both mechanical and nonmechanical failures, which can manifest as either early or late postoperative complications and may necessitate reoperation. The most common causes of surgical revision are pump migration or malfunction, liquid leakage from the connector, infection, urethral erosion, and urethral atrophy.

Overall, the AUS survival rate is around 90% at 1 year, 57% at 10 years, and 41% at 15 years [84]. A pooled analysis of complications showed mechanical failure in 6.2%, urethral atrophy in 7.9%, and a global reoperation rate for any reason in 26.0% of patients [77]. Urethral erosion or device infection typically results in AUS explantation. A second device implant is associated with a worse outcome [85].

Several competing devices have been introduced in recent years, including the VICTO (Promodon, Cordoba, Argentina) and the Zephyr ZSI 375 (Mayor Group, Villeurbanne, France) systems.

VICTO is an adjustable preconnected AUS. A small silicone balloon regulates the pressure in the occluding cuff, and the control pump has a self-sealing port for pressure adjustment [86]. The system pressure can be adjusted from 0 to 100 cm of

#### *Post-Prostatectomy Urinary Incontinence DOI: http://dx.doi.org/10.5772/intechopen.114136*

water. VICTO +, with an additional stress balloon placed in the preperitoneal region, is available for patients who were unable to interrupt the stream. Thereby, abdominal pressure changes are directly transferred to the urethral cuff [87].

Zephyr ZSI 375 is another all-in-one silicone-elastomeric device [88], without an abdominal reservoir and with an inflatable cuff in which pressure can be adjusted by instilling or abolishing fluid. Neither device is currently approved for use in the US.

#### *4.2.2 Male slings*

Male slings are polypropylene meshes positioned over the bulbar urethra via transobturator route [89]. The concept of the male sling was initially proposed by Berry in the 1970s and subsequently refined by Kaufman and Schaefer, resulting in the current medical device used in clinical practice [90]. Slings cure urinary incontinence by simple urethral compression and/or bulb repositioning to restore the preprostatectomy configuration of the prolapsed urethral sphincter complex [91].

Synthetic male slings are becoming increasingly common because they are reasonably inexpensive and do not require mechanical manipulation when voiding. Most experienced urologists recognize that selecting the correct patient is essential for successful treatment. Patients with mild-to-moderate SUI and adequate residual sphincter function, which allows for enough detrusor contraction to overcome the fixed sling impediment and allow voiding, are the best candidates [92].

Male slings are classified as adjustable and nonadjustable based on whether the tension can be adjusted or not after the procedure according to the patient's continence status [51].

Commercially available adjustable male slings are Argon (Promedon, Cordoba, Argentina), Re-Meex (Neomedic, Barcelona, Spain), and ATOMS (AMI, Feldkirch, Austria), while current nonadjustable male slings are AdVance (Boston Scientific, Minnetonka, MN, USA), I-STOP TOMS (CL Medical, Lyon, France), and Virtue (Coloplast, Minneapolis, MN, USA).

There are no studies that compare individual devices. As a result, determining the success rate of operations is difficult, and judging which sling system is superior is challenging [93].

AdVance XP sling is the evolution of AdVance sling (Boston Scientific, Marlborough, MA, USA), a retrourethral sling that contains polypropylene mesh. It is placed via a transobturator approach around the proximal bulbar urethra. To accurately position the sling, the central tendon of the perineum must be released. The mesh is then attached to the bulbous urethra, and the tension is applied so that the membranous urethra can be relocated further proximally. Continence is achieved through a 3–4 cm proximal elevation of the bulbar urethra [94].

The AdVance XP model, launched in 2010, has improved stability due to tensioning fibers, chevron anchors, and Tyvek (DuPont, Wilmington, DE, USA) liners. Furthermore, the implantation needle was modified to facilitate placement [95].

In our practice, we utilize a bulbospongiosus muscle-sparing surgical technique for the insertion of the AdVanceXP sling, with the aim to decrease postoperative complications (acute urinary retention and urethral erosion) [96]. The muscle-sparing approach consists of placing the sling directly on the bulbospongiosus muscle, unlike the standard technique, which requires the opening of the bulbospongiosus muscle and the placing of the sling on the underlying corpus spongiosum. The preservation of an intact and healthy proximal bulbar urethra is particularly desirable in failed patients requiring subsequent AUS implantation [96].

There is level 1 evidence that male sling can cure or improve PPUI with an overall success rate between 60 and 80% [97, 98]. Success is inversely correlated with SUI severity, with mild incontinence achieving success rates of 80–90%, even outperforming the AUS [99]. However, for those with moderate SUI, the AUS outperforms the sling, with sling success rates ranging from 32 to 83% [48, 75]. The severity of SUI has been associated with worse outcomes; therefore, patient selection is the key to success [94].

Failure rates after sling placement range from 15 to 45% and current knowledge of predictors of sling efficacy is limited [100].

Literature reports a postoperative complication rate ranging from 1 to 45% [101]. Perineal pain is the most common complaint, with an estimated rate as high as 45%. Urinary retention rates range from 2 to 23%, depending on the type of sling selected. Other uncommon complications include urethral erosion and infection. Revision rates are reported at approximately 1% [93, 94].

A recent noninferiority randomized controlled trial compared synthetic slings with AUS. The former was comparable to the latter in terms of continence rate improvements, symptoms, quality of life, and treatment-related satisfaction [98].

#### *4.2.3 Peri-urethral balloons*

The ProACT® (Uromedica, Inc., Plymouth, MN, USA) is a noncircumferential compressive device consisting of two silicone balloons that are implanted by a trocar via two small perineal incisions and are placed under fluoroscopic guidance on each side of the bladder neck, close to the vesicourethral anastomotic site. An outpatient procedure fills the balloons, resulting in mechanical compression of the urethra [102].

The potential benefits of the ProACT device include technical reliability of implantation, low morbidity, a low price, the absence of circumferential urethral compression, and the possibility to modulate the degree of urethral compression [103].

The efficacy is reported to be 55% (30–75%), but more than a third of patients were not satisfied with the outcome of the surgery [104]. The success rates are negatively impacted by the severity of incontinence and a prior history of radiation therapy, which some authors consider a contraindication [74, 105].

There is currently no direct recommendation in the European guidelines for using ProACT. These device implantations should be exclusively performed at specialized centers due to the specific surgical technique, the complexity of indications, and the potential risks of erosion, mechanical failure, and subsequent reoperation, with an estimated explantation rate of 25% [74].

#### *4.2.4 Bulking agents*

In patients with PPUI persistent and refractory to conservative management or in patients unfit for more invasive surgical treatment, bulking agents are an option that can be chosen [106].

Among all the bulking agents, polytetrafluoroethylene (Teflon) and bovine collagen have been the first two agents used. More recent elements are represented by adipose tissue (1989) and stem cells (2007) [107].

Based on a systematic review by Toia et al. [106], bulking agents can improve continence rates, at least in the short term.

Bulking agents are injected endoscopically into the sphincteric complex, increasing the sphincter's coaptation and resistance to flow [65]. A controversy exists on

#### *Post-Prostatectomy Urinary Incontinence DOI: http://dx.doi.org/10.5772/intechopen.114136*

injection volume and site, leading to variable functional improvements between different centers [106].

According to a recent meta-analysis, which compared the different devices used for treating PPUI, bulking agents are associated with the lowest improvement in continence after treatment. In addition, the more the injections are, the lower the continence rates and improvements are [108].
