Introduction

Radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion (UD) is the gold standard therapy for patients with muscle invasive bladder cancer and certain high-risk non-muscle invasive tumors [1, 2]. The choice of orthotopic neobladder (ONB), ileal conduit, or continent cutaneous urinary diversion is a critical one that depends on patient- and physician-related factors. Several oncologic, functional, and metabolic contraindications exist to ONB, including a positive urethral margin, urethral stricture disease, extensive gross extravesical disease, renal or hepatic dysfunction, and a physical or mental impairment to perform self-catheterization [3]. Despite these, most patients are eligible for an ONB and will choose one if offered [4, 5]. Perceived advantages of ONB include improved body image and the ability to have spontaneous voiding without an external appliance [6, 7]. However, recent series show that almost 90% of all patients undergoing RC in the USA today receive ileal conduit urinary diversion. The odds of receiving an ONB are higher for patients treated at academic or high-volume centers, suggesting the importance of surgeon comfort or experience with the procedure [8•, 9•]. While exact reasons for the disparity in urinary diversions are unknown, patient- and physician-reported reasons for choosing an incontinent diversion over ONB primarily include concerns over urinary functional outcomes [5].

The functional goals of ONB creation are to create a reservoir with similar function to the native bladder, with adequate low-pressure storage and socially acceptable voiding. Dysfunction in either domain, while not the norm, can occur and manifests as urinary incontinence or urinary retention. Herein, we explore voiding dysfunction after ONB, its etiology, treatment or prevention, and unique differences in male and female patients.

A Failure to Store—Urinary Incontinence

Incidence and Etiology

Despite concerns over urinary incontinence after ONB, adequate continence is achieved in the majority of patients. Reported rates of daytime continence vary from 70 to 100% after ONB [10,11,12,13,14,15,16,17,18,19], but can be as low as 50% in female patients [18]. Nighttime continence rates typically lag behind daytime rates and range from 50 to 95% [10,11,12,13,14,15,16,17,18] (Table 1). However, these numbers come mostly from older retrospective studies without patient-reported severity or documentation of continence over time. A recent series from our institution showed that continence is dynamic and improves with time. We studied 188 men who received ONB using a validated patient-reported pad usage questionnaire. Continence was defined as the use of no pads or pads that were essentially dry and for protection only. Daytime continence improved from 59% at 3 months after surgery and to 92% at 12–18 months after surgery. Nighttime continence similarly improved from 28% at 3 months to 51% at 18–36 months after surgery [15••]. A study by Anderson et al. documented the severity of incontinence in 49 female patients receiving ONB at their institution. At a median follow-up of 8.9 months, 57% were continent during the day. Incontinence was reported as mild (1 pad per day) in 29% of patients, moderate (2–4 pads per day) in 9%, and severe (5 or more pads per day) in 62%. Nighttime incontinence was present in 55% of patients and was mild in 59%, moderate in 7.4%, and severe in 14.8% [17].

Table 1 The incidence of voiding dysfunction after orthotopic neobladder
Full size table

Continence after ONB creation depends on the reservoir (adequate pouch capacity and pressure) and outlet (intact urethra and sphincter mechanism). The two most common types of neobladder performed are that of Hautman [10], which uses approximately 70 cm of ileum and Studer [20], which uses approximately 60 cm. Both rely on detubalarized segments of bowel that are reconfigured into a spherical shape. Detubularization serves to eliminate unwanted contractions that may increase pressure via peristaltic activity. Reconstruction of the detubularized bowel into a spherical shape allows for the greatest capacity as volume increases by the radius cubed. Similarly, a larger spherical radius provides for the lowest internal pressure per LaPlace’s law [21]. One purported reason for the improvement in continence over time is an increased capacity and decreased pressure as the bowel stretches. Median capacity for ileal ONBs typically increases to approach 500 cc after 1 year, regardless of technique [11, 22,23,24].

An intact external urinary sphincter is essential in achieving urinary continence. However, even if preserved, this sphincter is under autonomic voluntary control, which explains the lower rates of continence at night and slower time to nocturnal continence as compared with awake daytime continence. Nocturnal incontinence occurs from sphincter relaxation in conjunction with the lack of detrusor-sphincter feedback that existed prior to RC [25]. The relationship of pouch capacity, pressure, and sphincter function is clear in the nocturnal setting where incontinence is more likely to occur in patients with a relaxed sphincter, higher pouch pressures, and greater residual urine [26].

Techniques to Preserve Continence

Detubularization and creation of an ONB with adequate volume and pressure are essential in attaining proper reservoir storage for continence. An adequate ONB outlet can be obtained through meticulous apical dissection to provide urethral length and nerve sparing techniques. Preservation of nerve branches from the pelvic plexus and pelvic branch of the pudendal nerve is known to preserve control of the urinary sphincter and supporting pelvic floor [27,28,29], but also preserves sensation in the membranous urethra [30]. This preservation of sensation explains the ability of nerve sparing procedures to improve both daytime and nighttime continence, as some have suggested leakage of urine into the membranous urethra produces either a reflex or voluntary contraction of the external sphincter [25, 28].

In males, nerve sparing during RC is performed as in radical prostatectomy with preservation of the neurovascular bundles that traverse along the posterolateral plane of the prostate [31]. In females, the neurovascular tissue passes medial to the ureters and lateral to the cervix as well as in the paravaginal areas. Thus, vaginal wall dissection should not be performed more dorsal than the 2 and 10 o’clock positions if possible to minimize nerve injury [32].

Additional techniques that have been reported to avoid nerve injury and maintain urethral support during RC include pelvic organ sparing operations. In men, this includes prostate sparing RC and in females, uterine and vaginal sparing RC. A recent multi-center study from Europe by Voskulien et al. reported their experience with prostate sparing RC for BC. They included 185 patients who, after extensive evaluation to exclude prostate cancer or urothelial cancer at the bladder neck and prostatic urethra, underwent prostate sparing surgery. After a median of 7.5 years, daytime continence was 95.6% and nighttime was 70.2% [33•]. In our experience, we have performed prostate sparing RC and ONB in patients with benign disease to maintain sexual function, but the additional benefit in terms of continence does not appear great enough to outweigh the risks of local and prostatic urothelial recurrence [34]. Higher urinary retention rates are also a concern in older males.

On the other hand, reproductive organ sparing RC and ONB in select females with bladder cancer appears less controversial. Reports from our institution and others have shown the only predictors of reproductive organ involvement in females undergoing RC to be hydronephrosis, trigonal involvement, a palpable posterior bladder mass, and clinical node positive disease [35•, 36]. The benefits of sparing the vagina in women include avoidance of neurovascular dissection and benefits of sparing the uterus include longer urethral lengths and higher urethral closing pressures with resultant better continence [18••]. In the previously mentioned study by Anderson et al. that examined the severity of incontinence in females receiving ONB, the only predictor of daytime continence was prior hysterectomy [17]. We therefore now perform reproductive organ sparing RC in females without high-risk features.

Treatment of Incontinence

Treatment options for urinary incontinence after ONB are limited and consist mostly of conservative therapies, depending on the etiology and severity of incontinence. A detailed history of voiding patterns is essential in guiding treatment strategies. In both males and females, overflow incontinence must be ruled out as a source of incontinence and in females, neobladder-vaginal fistula must be ruled out. After this, first-line options are the same as they would be for any patient with a native bladder and stress urinary continence. These options include pelvic floor strengthening through Kegels exercises or formal pelvic floor physical therapy. Timed voiding is essential to prevent overflow incontinence during the day and particularly at nighttime as elevated residual volumes are a known risk factor for nighttime incontinence. There is currently no limit for what is considered a normal post-void residual for a neobladder, but in general should be less than 250 cc. Surgical options include urethral bulking agents and obstructive slings in women, though caution should be taken in retropubic dissection as patients are at greater risk of bowel or neobladder injury [37]. We have successfully placed artificial urinary sphincters in men with incontinence after ONB, and often times with concomitant inflatable penile prosthesis [38•]. This encourages a thorough preoperative discussion in men whose disease characteristics may limit a nerve sparing procedure.

A Failure to Empty—Urinary Retention

Incidence and Etiology

Emptying failure following ONB construction is a known, but uncommon risk of surgery. Definitions of emptying failure vary in the literature and include either a complete inability to void or a need for catheterization due to elevated residuals. Catheterization rates are more common in females and range from 15 to 43% [13, 16, 17, 39]. Catheterization rates in males vary from 3.9 to 43% [10,11,12,13,14,15] with rates of catheterization due a complete inability to void ranging from 1.7 to 5.3% of men [10, 14, 15] (Table 1).

The etiology of emptying failure after ONB has been attributed to mechanical obstruction or dysfunctional voiding, which has been described as post-void residual (PVR) > 100 cc without signs of obstruction. A study by Simon et al. of 655 male patients who received ONB found that 75 (11.5%) had at least one episode of emptying failure. The majority of cases (8%) were due to mechanical obstruction, which included benign anastomotic strictures, neobladder mucosal protrusion into the urethra, foreign bodies, and local tumor recurrence. All cases of obstruction were treated with either transurethral procedures or palliative chemotherapy, which resolved obstruction from tumor recurrence in 8/13 patients. The patients with dysfunctional voiding were managed indefinitely with intermittent catheterization [40]. Ji et al. performed a similar study in 231 males with ONB and found that 16% had emptying failure with 10.8% due to mechanical obstruction and 5.2% due to dysfunctional voiding [41]. We do not routinely instruct patients to perform catheterizations or to check PVRs if asymptomatic and our most recent study of male patients receiving ONB found a self-reported any catheterization rate of 10% with only 5.3% catheterizing due to an inability to void [15]. If patients are asymptomatic and have no hydronephrosis, electrolyte abnormality, incontinence, or recurrent infections, there is no indication to check post-void residuals.

An anatomic cause of emptying failure in women includes neocystocele formation where obstruction results from urethral angling and kinking due to downward displacement of the ONB neck and lack of periurethral support after hysterectomy or removal of the vagina. Finley et al. studied this phenomenon in an investigation of 21 female patients after ONB. All patients had undergone prior or concurrent hysterectomy. Emptying failure occurred in 7 (36.8%) patients with one due to stricture and the others due to neocystocele formation. Dynamic pelvic MRI was performed in 4 of these patients and they found an average ONB descent of 1.8 cm with voiding and average change in neocystourethral angle from resting to straining of 17.8 degrees. Intermittent catheterization was required in all patients but one who voided to completion only after manually reducing her prolapse [39].

The etiology of dysfunctional voiding is less understood and diagnosed only after exclusion of mechanical obstruction. Evacuation of urine in patients with ONB occurs through an increase in abdominal pressure through straining in conjunction with voluntary relaxation of the external sphincter. Again, reflex relaxation of the sphincter cannot occur after removal of the native bladder, but an intact pudendal nerve allows for voluntary sphincter relaxation [42]. A lack of coordination between sphincter relaxation and abdominal straining has been proposed. However, Steven and Poulsen evaluated 7 male patients with dysfunctional voiding after ONB using electromyography and found sphincteric relaxation present in all [11]. Other non-obstructive causes of urinary retention include elongation and kinking of the neobladder neck and progressive pouch enlargement with neobladder atony [43, 44].

Techniques to Prevent Emptying Failure

Several surgical principles in ONB creation ensure adequate emptying. Placement of the neourethra in the most dependent portion of the reservoir, prevention of excessive funneling of the neobladder neck, and creation of a small but adequate capacity reservoir have been described, but it is unclear whether these have significant impact on urinary retention or continence [14, 43, 44]. We perform a “modified” Studer pouch with neourethra at the distal end of the suture line [45] with similar continence rates to classic Studer or Hautman pouches (Table 1). The prevention of neocystocele formation in females may be accomplished with uterine or vaginal preservation. Some authors have suggested prophylactic sacrocolpopexy with fixation of the vaginal stump to prevent prolapse [46•, 47]. In a trial of 44 female patients who underwent RC with hysterectomy and ONB, Zyczkowski et al. randomized 24 to receive prophylactic sacrocolpopexy with an 8 × 3 cm polypropylene mesh. Only one patient required intermittent catheterization but mean PVRs were 65 cc in the study group and 184 cc in the control group [46]. We routinely perform sacrocolpopexy with either biologic or polypropylene mesh in all females receiving ONB at our institution.

Treatment of Emptying Failure

The treatment of patients with emptying failure should include a cystourethroscopy to rule out mechanical obstruction from rare causes such as anastomotic strictures and foreign bodies such as pouch stones and mucosal folds. The evaluation of mucosal fold as a causative factor for urinary retention can be made with the cystoscope near the bladder neck and the inflow off. Some groups have described transurethral resection of mucosal folds to relieve obstructing tissue although the experience and success of this procedure is limited [48]. Other causes of mechanical obstruction can be treated with transurethral procedures. A recurrence of disease in the urethra must also be ruled out and treated accordingly. Unfortunately, the treatment options for dysfunctional voiding are limited and essentially require intermittent catheterization.

Conclusion

While RC and urinary diversion remains the standard of care for patients with high risk or muscle invasive bladder cancer, almost 90% of patients receive incontinent diversions as opposed to ONB. Concerns over voiding dysfunction and misconceptions about urinary incontinence and retention, may in part drive this discrepancy. However, these problems are not common and may be prevented with careful patient selection and special technical considerations such as nerve sparing and organ sparing procedures when feasible. Future work will require more prospective and patient-reported studies to better characterize and understand voiding dysfunction after ONB. Treatment options for voiding dysfunction after ONB remain limited for both male and female patients and more effective options are needed.