Robotic Intracorporeal Orthotopic Neobladder: Urodynamic Outcomes, Urinary Function, and Health-related Quality of Life

Abstract

Background:

Intracorporeal orthotopic neobladder (iONB) creation following robotic radical cystectomy is an emerging procedure and robust functional data are required.

Objective:

To evaluate urodynamic features of iONB and bladder cancer–specific and general health-related quality-of-life (HRQOL) outcomes.

Design, setting, and participants:

We retrospectively assessed 28 men who underwent iONB creation (January 2012 to October 2013) and compared results to a previously characterized cohort of 79 of open ONB procedures.

Outcome measurements and statistical analysis:

iONB pressure-volume properties were characterized using multichannel urodynamics (UDS). The Bladder Cancer Index (BCI) questionnaire, modified with mucus- and pad-related questions, and the Short Form Health Survey (SF-36) were used to evaluate urinary function and HRQOL. ONB cohorts were compared for functional outcomes and BCI score. Multivariable linear regression was used to assess predictors of BCI score.

Results and limitations:

The median follow-up was 9.4 mo for the iONB and 62.1 mo for the open ONB group (p < 0.0001); ≥ 2-yr follow-up had been completed for one (4%) patient in the iONB group compared to 75 (95%) patients in the open ONB group (p < 0.0001). In UDS tests, the iONB group had minimal postvoid residual volume, normal compliance, and a mean capacity of 514 cm³ (range 339–1001). BCI mean scores for urinary function (p = 0.58) and urinary bother (p = 0.31) were comparable between the groups. The surgical approach was not associated with the BCI score on multivariable analysis. Rates of 24-h pad use were comparable between iONB and open ONB groups (pad-free 17% vs 19%; ≤2 pads 84% vs 79%), as reflected by total pad usage (p = 0.1); pad size and daytime wetness were worse in the iONB group. The clean intermittent catheterization rate was 10.7% in the iONB and 6.3% in the open ONB group. Limitations include the retrospective comparison, small number of patients and short follow-up for the iONB group.

Conclusions:

iONB had adequate UDS characteristics and comparable bladder cancer–specific HRQOL scores to open ONB. However, pad size and daytime wetness were worse for iONB, albeit over significantly shorter follow-up.

Patient summary:

We demonstrate that the volumetric and pressure characteristics are acceptable for a neobladder created using an entirely robot-assisted laparoscopic technique after bladder removal for cancer. Urinary function and quality-of-life outcomes related to the robotic technique were compared to those for neobladders created via an open surgical technique. We found that urinary function and bother indices were comparable; however, the robotic group required larger incontinence pads that were wetter during the daytime. This may be explained by the significantly shorter duration of recovery after surgery in the robotic group.

1. Introduction

There is significant uptake of robotic radical cystectomy (RRC) in the treatment of muscle-invasive bladder cancer. In appropriately selected patients, creation of an orthotopic neobladder (ONB) is the preferred urinary diversion at our center. Robotic creation of an intracorporeal ONB (iONB) has been demonstrated and adopted as part of a completely robotic cystectomy procedure [1]. Although there are data on the technical efficiency and complications related to robotic iONB, urodynamic functional assessments of intracorporeally constructed neobladders are lacking [2]. It remains to be seen whether entirely robotic creation of iONBs has comparable functional metrics and general and health-related quality of life (HRQOL) scores specifically related to orthotopic substitution, such as pad use.

The primary objective of this study was to report quantifiable urodynamic parameters to assess whether robotically created iONBs behave as low-pressure, high-volume reservoirs. As a secondary aim, validated instruments were used to compare continence outcomes and general and HRQOL scores related to orthotopic bladder substitution between robotic and open approaches.

2. Patients and methods

2.1. Study subjects

Consenting patients who underwent RRC and iONB were prospectively followed in a database approved by the institutional review board (IRB). Inclusion criteria included male patients, no technical complications directly related to neobladder that could impact neobladder function, and completion of at least 3-mo follow-up after surgery. We identified 39 patients who underwent robotic iONB creation between January 2012 and October 2013 by one of three robotic surgeons (M.A, M.D, or I.S.G). Three female patients were excluded and one patient had died at the time of follow-up. In addition, three patients with recent or planned open revisions at the time of this study for significant postoperative technical complications were excluded (two uretero-ileal strictures and one neobladder-small bowel fistula). After IRB approval, a total of 32 robotic iONB patients were contacted regarding study participation over the period from October to December 2013.

We previously established an open surgical cohort as part of an IRB-approved randomized controlled trial comparing the T-pouch diversion to the modified Studer ileal neobladder between 2002 and 2009. This served as the benchmark cohort for comparison of robotic iONB outcomes. We identified 79 male patients who underwent open Studer ileal ONB creation by separate surgeons at our institution and had completed a urinary function and bladder cancer–specific HRQOL questionnaire by mail at least 12 mo after surgery (response rate 179/295 for all diversions types) with a mean follow-up of 4.5 yr [3].

2.2. Outcome measures and covariates

We performed multichannel urodynamics (UDS) in consenting patients who had undergone robotic iONB. All UDS measurements were performed with the patient in a seated position. Noninvasive uroflowmetry and postvoid residual volume (PVR) was assessed at the start of the procedure. A dual-lumen 7F transurethral catheter was placed into the ONB, and a 7F rectal catheter was used to transduce the abdominal pressure. The ONB was filled at a rate of 50 ml/s until maximum cystometric capacity, defined by either leakage or abdominal discomfort. The change in volume per increase in pressure during the filling phase was used to calculate compliance (ml/cm H₂O). Although there is no widely accepted absolute normal compliance, it has been suggested that values >12.5–30 ml/cm H₂O represent the lower limit of normal [4,5]. At maximum cystometric capacity, provocative testing (Valsalva maneuver and coughing) was used to assess stress urinary incontinence and the abdominal leak-point pressure (ALPP). PVR was determined via catheterization or noninvasive PVR. A representative UDS tracing is depicted in Supplementary Figure 1.

We used the urinary function and bother components of the Bladder Cancer Index (BCI), a bladder cancer–specific HRQOL questionnaire, for which higher scores represent better health states [6]. Because there are HRQOL factors that are unique to orthotopic neobladder substitution, we also gathered additional data on mucus leakage and on pad number, size, timing (daytime or nighttime), and wetness [3]. Finally, the Short Form Health Survey (SF-36), which assesses psychometrically based physical and mental health summary measures, was used to assess non–disease-specific, generic quality of life [7]. These comprehensive questionnaires were administered to 28 consenting patients who had undergone robotic iONB creation either during clinic follow-up or via telephone interview. The previously established benchmark cohort of open ONB patients (n = 79) treated in our institution had already completed the BCI and HRQOL questionnaires, which we used to provide a contextual framework for interpretation. SF-36 scores for our iONB cohort were compared to literature values for open ONB procedures and US population norms [8].

Covariates of interest included time since surgery (in months), age at time of surgery (in years), American Society of Anesthesiologists physical status score (1–2 or 3–4), body mass index (BMI; ≤25, 25–30, or >30 kg/m²), presence of diabetes mellitus, previous radiation therapy, and neoadjuvant or adjuvant chemotherapy. Pathologic staging information included extravesical (>pT2b) or organ-confined (≤pT2b) disease and nodal status (categorical) according to the cancer staging manual (6th edition) of the American Joint Committee on Cancer.

2.3. Statistical analysis

Pearson’s χ² test or Fisher’s exact test was used to examine the association between surgical techniques and various categorical demographic and clinical variables. The Kruskal-Wallis test was used to examine differences in continuous variables between surgical techniques when data did not meet criteria for normality. Overall BCI scores and urinary function and urinary bother components were compared using the Wilcoxon two-sample test. Multivariable linear regression analysis was used to assess the relationship between BCI score and potential predictor variables. Covariates that were a priori deemed clinically important (time since surgery, age) and those meeting statistical significance (p < 0.1) on univariate analysis (BMI and diabetes mellitus) were mutually adjusted in multivariable models, which also included the variable of interest, surgical technique (robotic vs open). Patterns of clean intermittent catheterization (CIC), mucus leakage, and pad use were compared between the open and robotic groups using Fischer’s exact test and the χ² test. All p values reported are two-sided and p < 0.05 was considered statistically significant. SAS statistical software version 9.3 (SAS Institute, Cary, NC, USA) was used for all analyses.

3. Results

A total of 28/32 (88%) eligible male patients who underwent robotic iONB completed follow-up questionnaires. Of these 28 patients, 12 (43%) agreed to undergo multichannel UDS measurement. The mean preurodynamic PVR was 82 cm³ (range 0–325 cm³). None of the 12 patients exhibited detrusor (neobladder) overactivity during the cystometry filling phase. The average compliance was normal (mean 33 ml/cm H₂O, range 13–74) and nine of the 12 patients had compliance >30 ml/cm H₂O. The mean cystometric capacity was 514 cm³ (range 339–1001). The majority of the patients (11/12) reported a perceptible sensation of bladder fullness at an average volume of 227 cm³. Urinary incontinence on provocative testing (Valsalva maneuver or coughing) was noted in two patients with ALPP of 40 and 50 cm H₂O. The average flow rate during the voiding phase was 3.2 cm³/s (range 1–10). The mean PVR after the voiding phase was 268 cm³; five of the 12 patients required CIC to empty the neobladder after UDS evaluation.

The median follow-up was 9.4 mo (interquartile range [IQR] 6.6–12.9) for the robotic iONB group and 62.1 mo (IQR 46.8–81.4) for the open ONB group (p< 0.0001). Follow-up of ≥2 yr had been completed by one (4%) patient in the iONB group and 75 (95%) patients in the open ONB group (p< 0.0001). Sociodemographic, comorbidity, and primary tumor characteristics were well balanced between the robotic iONB and open ONB groups (Table 1).

Table 1 –

Demographic and clinical characteristics for patients undergoing robotic intracorporeal orthotopic neobladder (iONB) or open orthotopic neobladder (ONB) creation

	Robotic iONB (n = 28)	Open ONB (n = 79)	p value a
Median follow-up, mo (IQR)	9.4 (6.6–12.9)	62.1 (46.8–81.4)	<0.001 b
Time since surgery, n (%)			<0.001
≤24 mo	27 (96.4)	4 (5.1)
>24 mo	1 (3.6)	75 (94.9)
Median age, yr (IQR)	63.5 (54.5–70.0)	67.0 (58.0–73.0)	0.09 b
Age, n (%)			0.44
≤60 yr	13 (46.4)	25 (31.7)
61–70 yr	9 (32.1)	26 (32.9)
71–79 yr	5 (17.9)	25 (31.7)
≥80 yr	1 (3.6)	3 (3.8)
ASA score, n (%)			0.28
1–2	11 (39.3)	22 (28.2)
3–4	17 (60.7)	56 (71.8)
Body mass index, n (%)			0.33
≤25 kg/m2	7 (25.0)	20 (25.3)
25–30 kg/m2	10 (35.7)	39 (49.4)
>30 kg/m2	11 (39.3)	20 (25.3)
Diabetes mellitus, n (%)	4 (14.3)	10 (12.7)	0.83
Prior radiation therapy, n (%)	1 (3.5)	2 (2.5)	0.77
Pathological staging, n (%)			0.12
Organ-confined	24 (79.0)	56 (70.9)
Extravesical	4 (21.0)	23 (29.1)
Pathologic node positivity, n (%)	4 (14.3)	8 (10.1)	0.55
Neoadjuvant chemotherapy, n (%)	5 (17.9)	3 (3.8)	0.02
Adjuvant chemotherapy, n (%)	3 (10.7)	16 (20.3)	0.26

ASA = American Society of Anesthesiologists.

^aχ² test.

^bKruskal-Wallis test.

There was no significant difference in overall mean BCI score between robotic iONB and open ONB (69.5 vs 73.7; p = 0.44). Scores were also comparable for the constituent BCI domains. The score for the BCI urinary function domain was 44.5 for robotic iONB and 39.0 for open ONB (p = 0.58). The score for the BCI urinary bother domain was 88.3 for robotic iONB and 84.7 for open ONB (p = 0.31). After mutual adjustment for relevant clinical covariates, the technique for ONB construction (open or robotic) was not independently associated with the overall BCI score (Table 2). The presence of diabetes mellitus was independently associated with lower BCI scores.

Table 2 –

Predictors of overall Bladder Cancer Index (BCI) according to multivariable linear regression with mutual adjustment for other relevant covariates

Variable	Overall BCI score
	Estimate	95% CI	p value
Robotic technique (vs open)	−9.7	−20.3 to 0.8	0.07
Time since surgery (d)	−0.003	−0.008 to 0.001	0.17
Age (yr)	−0.01	−0.3 to 0.3	0.93
BMI 25–30 kg/m2 (vs ≤25)	−3.7	−11.3 to 3.9	0.34
BMI >30 kg/m2 (vs ≤25)	−3.2	−11.4 to 5.0	0.39
Diabetes (vs no diabetes)	−12.0	−20.9 to –3.1	0.009

CI = confidence interval; BMI = body mass index.

The complete continence rate (pad-free) at last follow-up was 17% for the robotic iONB and 19% for the open ONB group. Two or fewer pads were used by 84% of patients in the robotic iONB group and 79% in the open ONB group. There were no significant differences over a 24-h period between robotic iONB and open ONB groups, as reflected by total pads used (Table 3). Timing of pad use (day or night) tended towards both day and night use for the robotic iONB group (78%) compared to the open ONB group (50%; p = 0.005). The robotic iONB group reported the use of larger pads during daytime (p< 0.0001) and nighttime (p = 0.007) compared to the open ONB group. The degree of daytime pad wetness was worse in the robotic iONB group than in the open ONB group (p = 0.002), but wetness was comparable at night (p = 0.1). Finally, there was no significant difference in the frequency of mucus leakage between open ONB and robotic iONB procedures (p = 0.31).

Table 3 –

Patterns of pad use and mucus leakage for robotic intracorporeal orthotopic neobladder (iONB) and open ONB

Variable	Patients, n/N (%)		p value a
	Robotic iONB	Open ONB
Pads per 24 h			0.10
0	4/24 (16.7)	15/79 (19.0)
1–2	15/24 (62.5)	51/79 (64.6)
3–4	1/24 (4.1)	11/79 (13.9)
≥5	4/24 (16.7)	2/79 (2.5)
Pad use			0.005
Day only	0/23	5/64 (7.8)
Night only	5/23 (21.7)	27/64 (42.2)
Day/night	18/23 (78.3)	32/64 (50.0)
Pad size (daytime)			<0.0001
Mini	2/24 (8.3)	35/64 (54.7)
Small	7/24 (29.2)	2/64 (3.1)
Medium	2/24 (8.3)	17/64 (26.6)
Large/extra-large	13/24 (54.2)	10/64 (15.6)
Pad size (nighttime)			0.007
Mini	0/24 (0)	9/64 (14.1)
Small	5/24 (20.8)	3/64 (4.7)
Medium	4/24 (16.7)	22/64 (34.3)
Large/extra-large	15/24 (62.5)	30/64 (46.9)
Pad wetness (daytime)			0.002
Almost dry	5/24 (20.8)	33/63 (52.4)
Slightly wet	5/24 (20.8)	8/63 (12.7)
Wet	2/24 (8.3)	14/63 (22.2)
Soaked	6/24 (25.0)	3/63 (4.8)
Too variable to classify	6/24 (25.0)	5/63 (7.9)
Pad wetness (nighttime)			0.10
Almost dry	4/24 (16.7)	19/63 (30.2)
Slightly wet	5/24 (20.8)	12/63 (19.0)
Wet	2/24 (8.3)	15/63 (23.8)
Soaked	7/24 (29.2)	7/63 (11.1)
Too variable to classify	6/24 (25.0)	10/63 (15.9)
Mucus leakage			0.31
Every day	11/28 (39.3)	17/79 (21.5)
Once/wk	4/28 (14.3)	17/79 (21.5)
Less than once/wk	3/28 (10.7)	13/79 (16.5)
Not at all	10/28 (35.7)	32/79 (40.5)

^aχ² or Fischer’s exact test.

CIC was performed by 10.7% (n = 3) of robotic iONB and 6.3% (n = 5) of open ONB patients. There were no significant differences in CIC frequency, timing, or bother between the groups (Table 4).

Table 4 –

Pattern of clean intermittent catheterization (CIC) for robotic intracorporeal orthotopic neobladder (iONB) and open ONB

	Patients, n/N (%)		p value a
	Robotic iONB	Open ONB
CIC frequency			0.27
1–2 per d	2/3 (66.7)	4/5 (80)
3–4 per d	1/3 (33.3)	1/5 (20)
>4 per d	0/3	0/5
Always	0/3	0/5
Time from cystectomy to CIC			0.29
<6 mo	3/3 (100)	2/4 (50)
6–12 mo	0/3	1/4 (25)
>12 mo	0/3	1/4 (25)
CIC bother			0.29
None	2/3 (66.7)	1/5 (20)
Very small	0/3	2/5 (40)
Small	0/3	0/5
Moderate	0/3	2/5 (40)
Big	1/3 (33.3)	0/5

^aFischer’s exact test.

Mean responses to the eight domains of the SF-36 questionnaire from our robotic iONB cohort are presented in Table 5. These scores appear comparable to mean SF-36 scores reported in the literature for open ONB, although there are differences in the inclusion of female patients and follow-up period after surgery among various studies [9–13].

Table 5 –

Comparison of Short Form Health Survey (SF-36) scores between robotic intracorporeal orthotopic neobladder (iONB) and literature values for open ONB substitution ^a

	US general population norm [8]	Current study	Philip et al [9]	Autorino et al [10]	Dutta et al [11]	Hara et al [12]	Fujisawa et al [13]
Diversion type	N/A	Robotic intracorporeal ileal ONB (Studer)	Open ileal ONB (Studer)	Open modified Hautmann ONB	Open ileal ONB	Open ileal ONB	Open ONB (various methods)
Patients, n (female)	3844 (2203)	28 (0)	28 (3)	35 (0)	49 (8)	26 (0)	36 (10)
Median follow-up (mo)	N/A	9.4	15	28 a	33 a	50 a	31 a
Median age at surgery (yr)	N/A	64	66	64 a	64 a	62 a	61 a
SF-36 domain scores
General health	50	60	74	61	65 b	50 b	57
Physical functioning	51	79	77	76	75 b	80 b	79
Role limitations due to physical health	49	68	69	60	62 b	50 b	55
Bodily pain	51	78	78	72	82 b	75 b	71
Vitality	54	65	61	53	59 b	60 b	63
Emotional well being/mental health	54	83	87	64	79 b	70 b	72
Role limitations due to emotional problems	51	88	84	53	75 b	70 b	56
Social functioning	51	76	79	60	80 b	50 b	76

^aMean scores for each of the eight SF-36 domains are presented. The SF-36 contains 36 questions assessing each domain and a mean score is produced for each (range 0–100), with a higher score indicating a greater quality of life. Results for SF-36 telephone-administered norms from the US general population are presented for comparison (2005–2006, age 35–89yr).

^bExtrapolated from bar graph.

4. Discussion

To the best of our knowledge, this is the first study to assess UDS characteristics and orthotopic diversion-specific and generic HRQOL together with pertinent functional outcomes (patterns of pad use) following robotic iONB creation. UDS parameters confirmed that the robotic procedure created a low-pressure, high-volume ONB. BCI urinary function and bother scores were comparable between the open and robotic cohorts. Worse BCI scores were associated with diabetes, but not the surgical technique or other relevant clinical variables such as age and BMI. We observed worse daytime pad wetness and use of larger pad size in the robotic iONB cohort. Nighttime pad wetness was similar between the groups. Importantly,the follow-up time was significantly shorter for the robotic iONB than for the open ONB group (median 9.4 vs 62.1 mo; p< 0.001). The data are nonetheless informative, especially in light of the urodynamically confirmed low-pressure, high-volume ONB created using the robotic procedure; it is possible that improved continence may be seen during further follow-up in the robotic iONB cohort given that there is a lag of at least 12 mo before urinary incontinence plateaus [14].

Urinary functional outcomes after iONB have been poorly studied to date. Daytime and nighttime continence rates at 12 mo after iONB have been reported as 90% and 75%, respectively [2,15]. Others have also found that daytime continence was excellent (0–1 pads in 73% of cases) whereas nighttime continence was worse (poor continence in 53% of cases) [16]. Inferior functional (incontinence) outcomes in patients undergoing iONB procedures have been suggested by cross-institutional comparisons [17]. Taking advantage of the continuous nature of the BCI, we used multivariable linear regression to assess whether relevant clinical variables and the surgical technique (open or robotic) were associated with worse BCI scores. Compared to open ONB, the iONB cohort showed evidence of a lower overall BCI score (approximately 10 points) after adjusting for other relevant covariates including follow-up time, but the difference did not reach statistical significance (p = 0.07). While this difference may be clinically significant, a larger sample and longer followup for the iONB cohort are needed to reach definitive conclusions. Our analysis demonstrated a comparable number of pads used and a similar proportion of patients with pad-free continence in the open ONB and iONB groups. Pad-free continence rates following ONB have been reported as 48–77% for nighttime and 74–92% for daytime in European series [18,19], and 40–47% for nighttime and 67–87% for daytime in North American series [20,21]. The reason for the discrepancy from our rate of approximately 20% is unclear; this is a critical area requiring targeted improvement. The discrepancy could be because of differences in technique, including the different extirpative and diversion components of the procedure. However, we believe that the gradual return and development of external sphincter strength over time is the likely explanation for the daytime incontinence outcomes for iONB group. This is consistent with the observation that daytime continence depends on sphincter strength or maximum urethral closure pressure and that nighttime continence is multifactorial, with potentially modifiable factors related to functional ONB characteristics, including capacity [22].

In the robotic arena, the need for a time-efficient technique for intracorporeal urinary diversion balanced against its technically demanding learning curve led to the initial performance of straightforward techniques, including simple U-shaped neobladder configurations [16,23]. These approaches have rightly been criticized because of concerns regarding inadequate volume and the risk of excessive storage pressure [17]. By contrast, our technique completely recapitulates the open ONBs achieved at our institution and uses only intracorporeal suturing to perform double cross-folding to obtain a truly globular shape [1]. Specifically, we use 60 cm of ileum, of which the distal 44 cm comprises the globular neobladder and the proximal 15 cm comprises the afferent limb. Once the posterior plate is created robotically, it is rotated anticlockwise by 908 before urethra-neobladder anastomosis, followed by double cross-folding and true globularization of the neobladder. Our globular robotic iONBs achieved a mean cystometric volume of 514 cm³ (range 339–1001), which is consistent with mean volumes reported for open ONB series of 430–600 and 450–524 cm³ for Hautmann [24,25] and Studer [26–28] configurations, respectively. Furthermore, the ability to achieve high volumes at low pressure (high compliance) of the robotic iONB lends support to a low-pressure reservoir.

There are several limitations to this study. This is a retrospective study in which iONB was compared to a benchmark cohort of male patients who underwent open ONB creation at our institution as part of a clinical trial. Despite comparable sociodemographic and pathologic characteristics, the cohorts differ in enrollment. While our open ONB experience is extensive, with a three-decade-long track record, the robotic iONB procedures on which we report here are among the first cases in our institution and anywhere, and thus they reflect not only our learning curve but also the developmental curve for a novel procedure. Since open ONB surgery preceded robotic surgery at our institution, follow-up is considerably longer for the open cohort, making comparison suboptimal. This cohort nonetheless provided an important contextual framework for interpreting iONB questionnaire scores. In addition, we did not have UDS or SF-36 results from the open ONB cohort for comparison, and baseline iONB characterization was not available because of the retrospective nature of the study. While the BCI is a validated instrument, the components added to tailor HRQOL assessment to orthotopic diversion (questions on patterns of pad use and mucus), although published previously [3], are not validated. The above notwithstanding, our evaluation of iONB patients using functional data (not only pad number but also pad size, degree of wetness, and timing of incontinence) and a generic and a reliable bladder cancer–specific HRQOL instrument, and the benchmarking of results against open ONB are unique features of this analysis.

Demonstration of adequate volumetric and pressure properties and comparable generic and bladder cancer–specific HRQOL and functional characteristics to open ONB is a critical step in the adoption of entirely robotic cystectomy with iONB creation. Nevertheless, the entirely robotic procedure must be assessed in a randomized controlled setting to evaluate costs, perioperative morbidity, and functional, HRQOL, and oncologic outcomes. We believe that our study represents an important step forward in the continuing assessment of iONB efficacy via multiple metrics [29].

5. Conclusions

Our UDS data confirm that robotic iONB creation recapitulates the necessary characteristics of a high-volume, low-pressure reservoir. Robotic iONB appears to display comparable health states to open diversion using a multidimensional measure of bladder cancer–specific HRQOL. However, given that pad size and daytime wetness were worse, ongoing follow-up and prospective comparison are required to assess long-term urinary continence rates.