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Functional Results Following Vescica Ileale Padovana (VIP) Neobladder: Midterm Follow-up Analysis with Validated Questionnaires
EUROPEAN UROLOGY 57 (2010) 1045–1051
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Bladder Cancer
Functional Results Following Vescica Ileale Padovana (VIP) Neobladder: Midterm Follow-up Analysis with Validated Questionnaires Giacomo Novara a, Vincenzo Ficarra a,*, Anila Minja a, Vincenzo De Marco b, Walter Artibani b a
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Italy
b
Department of Biomedical and Surgical Sciences, Urology Clinic, University of Verona, Italy
Article info
Abstract
Article history: Accepted January 7, 2010 Published online ahead of print on January 16, 2010
Background: Orthotopic bladder reconstruction is the preferred method of urinary diversion following radical cystectomy (RC). Several papers reported functional data of different orthotopic neobladders, although to date, no one has used validated questionnaires. Objective: To evaluate the midterm functional results in a contemporary series of patients undergoing RC and vescica ileale Padovana (VIP) orthotopic neobladder by applying a set of validated questionnaires. Design, setting, and participants: We conducted a cross-sectional study at a single academic centre. Intervention: We included RC and VIP orthotopic techniques for bladder transitional cell carcinoma. Measurements: The American Urological Association Symptom Index (AUA-SI), the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ-UI SF), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate functional outcomes. Results and limitations: All 113 patients who were alive and disease free at 44-mo follow-up were evaluated. Sixteen patients (13%) were on clean intermittent catheterisation (CIC). The median AUA-SI score of the 97 voiding patients was 9 (interquartile range [IQR]: 4.5–16). Specifically, 48.5%, 40.2%, and 11.3% of the patients had mild, moderate, or severe lower urinary tract symptoms (LUTS), respectively. American Society of Anaesthesiologists class (odds ratio [OR]: 9.0; p = 0.03) and body mass index (OR: 1.5; p = 0.023) were independent predictors of the need for CIC, while only patient age at the time of surgery (OR: 0.920; p = 0.01) was predictive of LUTS severity. The median ICIQ-UI SF score was 6 (IQR: 3–10). Twenty patients (17.7%) were fully continent, while 31.9%, 35.4%, and 15% had slight, moderate, and severe incontinence, respectively. About 90% of the patients during the day and 80% during the night used no pad or only a safety pad. Most of the patients leaked when asleep. No variable was predictive of return to continence. Finally, roughly 20% of the male patients were potent, having an IIEF-5 score 17. Conclusions: We reported midterm functional outcomes following RC and VIP neobladder using validated questionnaires. On the whole, the results are encouraging. However, in the absence of patient self-completed questionnaires, functional outcomes may be significantly overestimated.
Keywords: Transitional cell carcinoma Cystectomy Orthotopic ileal neobladder Urinary incontinence
# 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Monoblocco Ospedaliero – IV Floor, Via Giustiniani 2 – 35128, Padua, Italy. Tel. +39 049 8212720; Fax: +39 049 8218757. E-mail address: vincenzo.fi[email protected] (V. Ficarra). 0302-2838/$ – see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2010.01.007
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1.
EUROPEAN UROLOGY 57 (2010) 1045–1051
Introduction
function (creatinine level <2 ng/ml or creatinine clearance >40 ml/min), and patient requests for orthotopic bladder substitution. Common
In the last decades, orthotopic bladder reconstruction emerged as the standard of care and preferred method of urinary diversion for patients undergoing radical cystectomy (RC) for bladder cancer in referral centres from Western countries [1]. Several reports demonstrated the long-term safety of the procedure in terms of oncologic outcome [1–4], metabolism consequences [1,5], and renal function preservation [1,2,6]. With regard to functional outcome following orthotopic bladder reconstruction, 75–95% of patients were reported to be continent during the day [1,5,7,9–14] and 50–90% during the night [1,5,8–14], while 3–35% of patients used clean intermittent catheterisation (CIC) to void the neobladder [5,8,10,11,13]. Finally, although erectile function is not related to urinary diversion, 10–30% of patients reported erections after cystectomy [5,15,16]. Despite the large number of available papers, most of these data consider only three neobladder types—hemiKock, Stude, and Hautmann [1]—and none of the available surgical series use validated questionnaires to evaluate functional outcomes. Patient self-completed questionnaires, indeed, represent the most important clinical tool for evaluating symptom impact and treatment benefit from a patient perspective [17]. Validated questionnaires provide a method for a standardised collection of data and an objective assessment of a subjective phenomenon, limiting the impact of the clinicians’ assessments of patients’ outcomes and heterogeneity among the different series. Several validated questionnaires are available for evaluating lower urinary tract symptoms (LUTS), urinary continence, and erectile function, including the American Urological Association Symptom Index (AUA-SI) [18], the International Consultation on Incontinence Questionnaire– Urinary Incontinence Short Form (ICIQ-UI SF) [19], and the five-item version of the International Index Erectile Function (IIEF-5) [20]. Our usual choice for urinary diversion after RC is the vescica ileale Padovana (VIP) neobladder, an original technique that our group proposed in 1990 [21] but whose functional results have not been reported. The purpose of the present study was to evaluate the midterm functional results in a contemporary series of patients undergoing RC and VIP orthotopic ileal neobladder for transitional cell carcinoma (TCC) of the bladder by applying a set of validated questionnaires.
contraindications were preoperative stress urinary incontinence; significant patient comorbidity; and patients unwilling, unfit, or—in the surgeon’s judgment—unable to comply with the voiding pattern required by the reservoir. Ten different surgeons performed all the procedures. All patients underwent pelvic-iliac lymphadenectomy with en bloc RC as described by Skinner and Lieskovsky [23]. Preservation of the neurovascular bundles was not routinely performed. With regard to orthotopic ileal neobladder, all patients underwent reconstruction of the neobladder using the VIP technique [21,24]. Briefly, a portion of terminal ileum 40 cm long is isolated approximately 20 cm proximal to the ileocecal valve and opened along the antimesenteric border. The distal 10-cm segment is intended to constitute a funnel for ileal-urethral anastomosis, while the proximal 30-cm segment of ileum is folded in a jellyroll fashion to produce a posterior plate. The pouch is then closed anteriorly. Patients did not undergo neoadjuvant chemotherapy, although adjuvant chemotherapy was proposed in cases of pathologic lymph node involvement. Patients with neobladder were instructed to void every 3 h during the day through simultaneous relaxation of the pelvic floor musculature and the raising of intra-abdominal pressure with a Valsalva manoeuvre. Moreover, they were encouraged to limit fluid intake after the evening meal, to void before going to sleep, and to set an alarm clock to awaken and void once or twice during the night. Patient performance status (PS) was evaluated according to the Eastern Cooperative Oncology Group (ECOG) classification [25], while patient comorbidity was assessed by the Charlson Comorbidity Index (CCI) [26]. American Society of Anaesthesiologists (ASA) score was used to estimate perioperative risk [27]. Clinical staging was reported according to the 2002 TNM system [28]. Median patient follow-up was 44 mo (interquartile range [IQR]: 30–58). At follow-up, 68 patients (34%) experienced cancer-related death, while 14 patients (7%) died of other causes. Six patients (3%) were alive with disease progression, and 113 patients (56%) were alive and disease free. The patients alive and disease free were evaluated in a cross-sectional fashion, being invited during follow-up visits to self-fill the Italian validated translations of the AUA-SI [18], ICIQ-UI SF [19], and IIEF-5 [20] questionnaires. Moreover, patients were asked how many liners they used during both the day and night and about the use of proerectogenic drugs. LUTS were graded in mild (AUA-SI 7), moderate (AUA-SI 8–19), and severe (AUA-SI > 20) according to the overall score. Moreover, storage (questions 2, 4, and 7) and voiding (questions 1, 3, 5, and 6) subscores were provided [18]. The severity of urinary incontinence was graded as suggested by Klovning et al [29]. Specifically, patients with a ICIQ-UI SF score of 0 were considered fully continent; patients with scores ranging from 1 to 5, 6 to 12, 13 to 18, and 19 to 21 defined slight, moderate, severe, and very severe incontinence, respectively. Postoperative erectile dysfunction was graded as mild (IIEF-5 scores 22–25), mild to moderate (IIEF-5 scores 17–21), moderate (IIEF-5 scores 11–16), and severe (IIEF-5 scores 6–10) as suggested by Cappelleri et al [20]. All procedures were in accordance with the ethical standards established in our country.
2.
Materials and methods
Internal review board approval was not required for such a nonexperimental study.
From January 2002 to December 2006, 201 patients underwent RC and orthotopic ileal neobladder for nonmetastatic bladder TCC at the
2.1.
Statistical analysis
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Italy. The indications for RC included tumour invasion
Continuous, normally distributed variables were reported as the
of the muscularis propria; high-grade invasive bladder tumours or
mean value standard deviation (SD). Continuous non-normal vari-
carcinoma in situ; or recurrent, multifocal, non–muscle-invasive disease
ables were presented as the median values and IQR. Fisher exact test and
refractory to intravesical immunotherapy [22]. Indications for orthotopic
the Pearson x2 test were used to compare the distribution of categoric
ileal neobladder included absence of locally advanced disease, absence of
variables. Mann-Whitney U and Kruskal-Wallis H tests were used to
disease at the level of the bladder neck and prostatic urethra, normal renal
compare two or more independent samples. Binary regression was used
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<0.05 was considered statistically significant. All data were analysed
Table 1 – Clinical and pathologic characteristics of 113 evaluated patients
using the Statistical Package for the Social Sciences v.16.0 (SPSS,
Variables
for multivariable analysis. For all statistical analyses, a two-sided p value
Cases
Chicago, IL, USA).
3.
Results
Table 1 summarises the clinical and pathologic characteristics of the 113 analysed patients. 3.1.
Lower urinary tract symptoms
Sixteen patients (13%) were on CIC. The median AUA-SI of the 97 patients who voided spontaneously was 9 (IQR: 4.5–16). Specifically, the median storage subscore was 3 (IQR: 1–4), while the median voiding subscore was 5.5 (IQR: 0–12). Finally, 47 patients (48.5%) had mild, 39 (40.2%) moderate, and 11 (11.3%) severe LUTS, respectively. Table 2 summarises all the findings of the AUA-SI. Compared to those voiding spontaneously, the patients needing CIC had significantly higher body mass index (BMI) scores (26.1 2.8 vs 29 2; p = 0.016), worse ECOG PS ( p = 0.018), and a higher ASA class (0.031). On multivariable analysis, when excluding ECOG PS because of colinearity with ASA class, both ASA class (OR: 9.0; p = 0.03) and BMI (OR: 1.5; p = 0.023) were independent predictors of the need for CIC (Table 3). LUTS severity, indeed, was significantly associated with patient age at the time of surgery ( p = 0.007) and CCI ( p = 0.034), with patients who reported moderate to severe LUTS being younger and having lower CCI scores compared to those with mild LUTS (Table 4). On multivariable analysis, only patient age retained an independent predictive value (OR: 0.920; p = 0.01; Table 4).
Gender, no. (%): Male Female BMI, mean SD
26.4 2.9
ECOG PS, no. (%): 0 1 2
67 (59) 36 (32) 10 (9)
ASA class, no. (%): I II III
15 (13) 67 (59) 31 (28)
CCI, median (IQR) Clinical T stage: T1 T2 T3 Clinical N stage, no. (%): N0 N+ Pathologic T stage, no. (%): T1 T2 T3 T4 Pathologic N stage, no. (%): N0 N1
Urinary incontinence
The median ICIQ-UI SF score was 6 (IQR: 3–10). On the whole, 20 patients (17.7%) were fully continent, while 36 (31.9%), 40 (35.4%), and 17 (15%) patients had slight, moderate, and severe incontinence, respectively. Seventyseven (68%) of our patients used no pad, 26 (23%) used a safety pad for occasional leakage, and 10 (9%) used one or more pads during the day. During the night, 26 (23%), 70 (62%), and 17 (15%) patients used no pad, a safety pad for occasional leakage, or one pad or more, respectively. In general, those using protection reported using a median number of one pad (IQR: 1–1), during both the day and the night. According to question 3 of the ICIQ-UI SF, the overall interference of urinary incontinence on patients’ everyday life was limited (median: 1.5; IQR: 0–5). According to question 4 on the ICIQ-UI SF, 59% of the patients leaked when asleep. Table 5 summarises all the findings of the ICIQ-UI SF questionnaire. None of the preoperative variables turned out to be predictive of the presence of any grade of or severe urinary incontinence at follow-up, even in univariable analysis (Table 6).
0 (0–1)
57 (50) 55 (49) 1 (1)
107 (95) 6 (5)
66 25 15 7
(58) (22) (13) (7)
104 (92) 9 (8)
SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; ASA = American Society of Anaesthesiologists; CCI = Charlson Comorbidity Index; IQR = interquartile range.
3.3. 3.2.
105 (92.9) 8 (7.1)
Erectile function
At follow-up, only 96 out of 105 patients filled out the IIEF-5 questionnaire. The median IIEF-5 score of those patients was 5 (IQR: 5–17.7). Considering all patients who did not fill the questionnaires impotent, 7 men (6.6%) had mild to moderate erectile dysfunction, and 18 men (17.1%) had mild erectile dysfunction, 10 with the assistance of phosphodiesterase type 5 inhibitors. 4.
Discussion
The VIP neobladder is an original technique for bladder substitution following RC developed in our centre in the late 1980s and reported for the first time by our group in 1990 [21]. To date, VIP is the second most commonly used neobladder in Italy, being used by 50 out of the 157 urological centres involved in a specific survey performed in 2006 [30]. In the present study, we used validated questionnaires to evaluate LUTS, urinary continence, and erectile function after RC with VIP neobladder. At a median follow-up of 44 mo, about 90% of the spontaneously voiding patients reported mild or moderate LUTS, although 13% needed CIC.
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Table 2 – Detailed data of the American Urological Association Symptom Index in 97 patients voiding spontaneously AUA-SI
Score, median (IQR)
Q1: Over the last month or so, how often have you had a sensation of not emptying your bladder completely after you finished urinating? Q2: During the last month or so, how often have you had to urinate again less than 2 hours after you finished urinating? Q3: During the last month or so, how often have you stopped and started again several times when you urinated? Q4: During the last month or so, how often have you found it difficult to postpone urination? Q5: During the last month or so, how often have you had a weak urinary stream? Q6: During the last month or so, how often have you had to push or strain to begin urination? Q7: During the last month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning? If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? Storage subscore (questions 2, 4, and 7) Voiding subscore (questions 1, 3, 5, and 6) Overall score
0 (0–1) 0 2 0 0 2 2
(0–1) (0–5) (0–0) (0–3) (0–5) (1–3)
0 (0–0) 3 (1–4) 5.5 (0–12) 9 (4.5–16)
Severity of LUTS, no. (%): Mild Moderate Severe
47 (48.5) 39 (40.2) 11(11.3)
AUA-SI = American Urological Association Symptom Index; IQR = interquartile range; LUTS = lower urinary tract symptoms.
Table 3 – Preoperative predictors of the need of clean intermittent catheterisation Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
CIC
Univariable analysis p value
No (n = 97)
Yes (n = 16)
90 (93) 61.7 8.9 26.1 2.8 48 (55) 0 (0–1) 59 (68) 47 (48) 94 (97)
14 (93) 65.5 7 29 2 5 (36) 1 (0–2) 6 (42) 7 (47) 14 (93)
Multivariable analysis OR; 95% CI
1 0.158 0.016 0.018 0.316 0.031 0.132 0.445
– – 1.5; 1.06–2.15 – – 9.0; 1.1–71-8 – –
p value – – 0.023 – – 0.03 – –
CIC = clean intermittent catheterisation; OR = odds ratio; CI = confidence interval; SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
Table 4 – Preoperative predictors of postoperative lower urinary tract symptoms severity Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
LUTS
Univariable analysis p values
Mild (n = 47)
Moderate (n = 39)
Severe (n = 11)
43 (95) 65 7.3 25.8 2.2 18 (51) 1 (0–2) 26 (74) 22 (47) 46 (98)
37 (95) 59.1 9.7 26.3 3.3 23 (72) 0 (0–0) 26 (81) 20 (51) 38 (97)
10 (91) 57.6 7.7 25.8 3.1 7 (78) 0 (0–1) 7 (78) 5 (45) 10 (91)
Multivariable analysis OR; 95% CI
0.807 0.007 0.863 0.282 0.034 0.404 0.745 0.632
– 0.92; 0.86–0.98 – – 0.72; 0.46–1.18 – – –
p value – 0.01 – – 0.15 – – –
LUTS = lower urinary tract symptoms; OR = odds ratio; CI = confidence interval; SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
Considering as continent those patients using no pad or a safety pad, about 90% and 80% of our patients achieved daytime and night-time continence, respectively. However, based on the strict ICIQ-UI SF criteria, <20% of the patients were fully continent, although most of the patients reported incontinence of slight to moderate severity. Finally, roughly 25% of the male patients were potent. Some clinical characteristics of the patients (mainly age, BMI, ASA class,
and CCI score) were predictive of the need of CIC and LUTS severity. Our 13% of CIC is similar to those scores previously reported in the literature, where 3–35% of the patients used CIC to void the neobladder [5,8,10,11,13]. The wide range of proportion of patients in CIC might reflect differences in surgical technique, patient characteristics, follow-up duration, and so on. However, our finding that BMI was
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Table 5 – Detailed data of the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form questionnaire in our cohort of patients ICIQ-UI SF
Cases, no. (%)
Q1: How often do you leak urine? Never About once a week or less often 2 or 3 times a week About once a day Several times a day All the time
24 (21.2) 35 (31) 27 (23.9) 15 (13.3) 9 (8) 3 (2.7)
Q2: How much urine do you usually leak? None A small amount A moderate amount A large amount
22 (19.5) 75 (67.2) 13 (11.5) 2 (1.8)
Q3: Overall, how much does leaking urine interfere with your everyday life? median (IQR) 1.5 (0–5) Q4: When does urine leak? Never Leaks before you can get to the toilet Leaks when you cough or sneeze Leaks when you are asleep Leaks when you are physically active/exercising Leaks when you have finished urinating and are dressed Leaks for no obvious reason Leaks all the time Overall score, median (IQR)
16 (14.1) 5 (4.4) 17 (15) 67 (59.3) 8 (7.1) 0 (0) 13 (11.5) 2 (1.8) 6 (3–10)
Severity of the incontinence: Fully continent (score 0) Slight incontinence (score 1–5) Moderate incontinence (score 6–12) Severe incontinence (score 13–18)
20 36 40 17
(17.7) (31.9) (35.4) (15)
ICIQ-UI SF = International Consultation on Incontinence Questionnaire– Urinary Incontinence Short Form; IQR = interquartile range.
significantly associated with the need for CIC in multivariable analysis might reconfirm that the funnel-shaped outlet could increase the risk of obstruction resulting from kinking in obese patients, as suggested by Studer et al [5]. Likely, a modification of the VIP surgical technique should be tested in order to attempt to reduce the rate of CIC in such patients. Because of the specific selection of questionnaires for evaluating functional outcomes, most of our data are not
comparable to those previously reported in other surgical series. With regard to LUTS, Madersbacher et al evaluated a series of 83 patients at a median follow-up of 95 mo with the use of frequency–volume charts, reporting a mean of 4.3 0.5 micturitions during the day and 2.0 0.7 micturitions during the night [31]. Although obtained using a different tool, the median storage subscore of the AUA-SI in our series reconfirms similar results. Our finding that age was an independent predictor of LUTS severity, with younger patients more commonly experiencing severe symptoms, was original and difficult to explain. The inability to correlate these figures with a preoperative baseline evaluation, during which older patients were more likely to report worse symptoms, prevents us from drawing definitive conclusions on this issue, which, indeed, can be identified only in prospective studies. Regarding urinary continence, the published series with longer follow-up durations reported daytime and nighttime continence rates ranging from 75% to 95% [1,5,7,9–14] and from 50% to 90% [1,5,8–14], respectively. All these studies reported as continent those patients not using any pad or condom or, in some series, those patients using a safety pad for occasional leakage, as well. Applying these two criteria, about 69% and 91% of our patients might be considered continent during the day and 25% and 85% during the night, respectively. The data from the ICIQ-UI SF, indeed, showed that by applying standardised, validated, patient-reported criteria, significantly lower figures can be obtained, with perfect continence being rare—definitively more realistic data patients should be aware of before surgery. None of the analysed clinical variables turned out to be significantly associated with continence recovery at follow-up, likely because of the small sample size. Finally, about 23% of our patients reported having mild to moderate or mild erectile dysfunction. The data are similar to those previously reported in the literature for RC, where 10–30% of patients are potent [5,15,16]. Specifically, Zippe et al reported on a small series of 49 patients, 14% of them being potent, with a mean IIEF-5 score of 16.6 4.9 at a mean follow-up of 44.4 mo [16]. Kessler et al, evaluating a series of 331 patients in which unilateral or bilateral preservation of the neurovascular bundles was attempted in 65.9% and 11.5% of the patients, respectively, reported 2-yr potency rates as high as 30% and 60% in case of the unilateral and bilateral nerve-sparing procedure, respectively [15]. Such
Table 6 – Preoperative prognostic factors predictive of any grade of and severe incontinence Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
Fully continent patients (n = 20)
Patients with any grade of incontinence (n = 93)
p values
Patients with severe incontinence (n = 17)
19 (95) 62.5 4 26.3 3.9 10 (50) 2 (1–3) 14 (70) 13 (65) 18 (90)
86 (92) 61.7 9.5 26.4 2.3 44 (62) 2 (1–4) 52 (73) 42 (45) 91 (98)
1 0.810 0.595 0.621 0.297 0.879 0.445 0.143
15 61.4 10 26.7 2.8 9 (53) 2 (1–5) 12 (70) 9 (53) 16 (94)
p values
0.414 0.908 0.631 0.916 0.719 0.374 0.549 0.484
SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
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a finding was surprising, considering that neurovascular bundle preservation was not routinely performed in our patients. Considering the young patient age, the lack of comorbidity, and the long follow-up, it might be hypothesised that nerve regeneration may have occurred following partial preservation and also that the presence of interindividual anatomic variations in the distribution of the nerve supply might have been present. However, the study design and the lack of other data at long-term follow-up from other series do not allow us to provide definitive conclusions on these issues. The major strengths of the present study are the use of validated questionnaires to evaluate functional outcomes and the longer follow-up. Because of the relatively long median follow-up, those patients are at low risk of cancerrelated death; consequently, those functional data can likely be considered those of cancer survivors after cystectomy. On the whole, these data provide an accurate picture of the midterm functional outcomes of VIP orthotopic neobladder from a strict patient perspective and are of interest for preoperative patient counselling as well as for comparisons of the performance of different neobladders when similar validated tools will be applied in other series. There are some limitations to our study, the largest of which is the limitation inherent to cross-sectional analyses, which did not allow us to evaluate preoperative functional outcomes and their impact on status at follow-up. In addition, the sample size was not particularly large, mainly because of cancer-related mortality. Consequently, some of our statistical analyses were underpowered. A third limitation was the large number of surgeons performing neobladder procedures in our series, which could have affected the study results. Fourth, because of the lack of specific questionnaires developed to assess urinary continence following orthotopic neobladder, we selected to use the ICIQ-UI SF because of the robust psychometric properties of the questionnaire and the extensive number of studies using such a tool in the evaluation of patients with different types of urinary incontinence [17]. However, the questionnaire had never been used in this clinical setting. Finally, the low number of female patients and the lack of validated Italian translations of questionnaires evaluating female sexual dysfunction prevent us from assessing that issue. 5.
Conclusions
Author contributions: Vincenzo Ficarra had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Novara, Ficarra, Artibani. Acquisition of data: Minja, De Marco. Analysis and interpretation of data: Novara. Drafting of the manuscript: Novara. Critical revision of the manuscript for important intellectual content: Ficarra, De Marco, Artibani. Statistical analysis: Novara. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Artibani. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.
References [1] Hautmann RE, Abol-Enein H, Hafez K, et al. Urinary diversion. Urology 2007;69(Suppl 1A):17–49. [2] Pycha A, Comploj E, Martini T, et al. Comparison of complications in three incontinent urinary diversions. Eur Urol 2008;54:825–34. [3] Froehner M, Brausi MA, Herr HW, Muto G, Studer UE. Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009;56:443–54. [4] Freeman JA, Tarter TA, Esrig D, et al. Urethral recurrence in patients with orthotopic ileal neobladders. J Urol 1996;156:1615–9. [5] Studer UE, Burkhard FC, Schumacher M, et al. Twenty years experience with an ileal orthotopic low pressure bladder substitute— lessons to be learned. J Urol 2006;161–6. [6] Thoeny HC, Sonnenschein MJ, Madersbacher S, et al. Is ileal orthotopic bladder substitution with an afferent tubular segment detrimental to the upper urinary tract in the long term? J Urol 2002;168: 2030–4. [7] Abol-Enein H, Ghoneim MA. Functional results of orthotopic ileal neobladder with serous-lined extramural ureteral reimplantation: experience with 450 patients. J Urol 2001;165:1427–32. [8] Stein JP, Lieskovsky G, Ginsberg DA, et al. The T pouch: an orthotopic ileal neobladder incorporating a serosal lined ilealantireflux technique. J Urol 1998;159:1836–42. [9] Hautmann RE, de Petriconi R, Gottfried HW, et al. The ileal neo-
Using validated questionnaires to evaluate LUTS, urinary continence, and erectile function after RC and VIP neobladder, we observed that most of the spontaneously voiding patients reported mild or moderate LUTS, although 13% needed CIC. Considering as continent those patients using no pad or a safety pad, about 90% of the patients were continent during the day and 80% were continent during the night. However, <20% of the patients were fully continent according to strict ICIQ-UI criteria. Finally, roughly 20% of the male patients had only mild to moderate or mild erectile dysfunction. The use of validated questionnaires to evaluate functional outcomes after RC and orthotopic neobladder should be strongly recommended.
bladder: complications and functional results in 363 patients after 11 years of followup. J Urol 1999;161:422–7. [10] Kulkarni JN, Pramesh CS, Rathi S, Pantvaidya GH. Long-term results of orthotopic neobladder reconstruction after radical cystectomy. BJU Int 2003;91:485–8. [11] Skolarikos A, Deliveliotis C, Alargof E, et al. Modified ileal neobladder for continent urinary diversion: functional results after 9 years of experience. J Urol 2004;171:2298–301. [12] Kato M, Takeda A, Saito S, et al. Long-term functional outcomes of ileal and sigmoid orthotopic neobladder procedures. Urology 2007; 69:74–7. [13] Granberg CF, Boorjian SA, Crispen PL, et al. Functional and oncological outcomes after orthotopic neobladder reconstruction in women. BJU Int 2008;102:1551–5.
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[19] Avery K, Donovan J, Peters TJ, et al. ICIQ: a brief and robust measure
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available at www.sciencedirect.com journal homepage: www.europeanurology.com
Bladder Cancer
Functional Results Following Vescica Ileale Padovana (VIP) Neobladder: Midterm Follow-up Analysis with Validated Questionnaires Giacomo Novara a, Vincenzo Ficarra a,*, Anila Minja a, Vincenzo De Marco b, Walter Artibani b a
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Italy
b
Department of Biomedical and Surgical Sciences, Urology Clinic, University of Verona, Italy
Article info
Abstract
Article history: Accepted January 7, 2010 Published online ahead of print on January 16, 2010
Background: Orthotopic bladder reconstruction is the preferred method of urinary diversion following radical cystectomy (RC). Several papers reported functional data of different orthotopic neobladders, although to date, no one has used validated questionnaires. Objective: To evaluate the midterm functional results in a contemporary series of patients undergoing RC and vescica ileale Padovana (VIP) orthotopic neobladder by applying a set of validated questionnaires. Design, setting, and participants: We conducted a cross-sectional study at a single academic centre. Intervention: We included RC and VIP orthotopic techniques for bladder transitional cell carcinoma. Measurements: The American Urological Association Symptom Index (AUA-SI), the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ-UI SF), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate functional outcomes. Results and limitations: All 113 patients who were alive and disease free at 44-mo follow-up were evaluated. Sixteen patients (13%) were on clean intermittent catheterisation (CIC). The median AUA-SI score of the 97 voiding patients was 9 (interquartile range [IQR]: 4.5–16). Specifically, 48.5%, 40.2%, and 11.3% of the patients had mild, moderate, or severe lower urinary tract symptoms (LUTS), respectively. American Society of Anaesthesiologists class (odds ratio [OR]: 9.0; p = 0.03) and body mass index (OR: 1.5; p = 0.023) were independent predictors of the need for CIC, while only patient age at the time of surgery (OR: 0.920; p = 0.01) was predictive of LUTS severity. The median ICIQ-UI SF score was 6 (IQR: 3–10). Twenty patients (17.7%) were fully continent, while 31.9%, 35.4%, and 15% had slight, moderate, and severe incontinence, respectively. About 90% of the patients during the day and 80% during the night used no pad or only a safety pad. Most of the patients leaked when asleep. No variable was predictive of return to continence. Finally, roughly 20% of the male patients were potent, having an IIEF-5 score 17. Conclusions: We reported midterm functional outcomes following RC and VIP neobladder using validated questionnaires. On the whole, the results are encouraging. However, in the absence of patient self-completed questionnaires, functional outcomes may be significantly overestimated.
Keywords: Transitional cell carcinoma Cystectomy Orthotopic ileal neobladder Urinary incontinence
# 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Monoblocco Ospedaliero – IV Floor, Via Giustiniani 2 – 35128, Padua, Italy. Tel. +39 049 8212720; Fax: +39 049 8218757. E-mail address: vincenzo.fi[email protected] (V. Ficarra). 0302-2838/$ – see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2010.01.007
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1.
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Introduction
function (creatinine level <2 ng/ml or creatinine clearance >40 ml/min), and patient requests for orthotopic bladder substitution. Common
In the last decades, orthotopic bladder reconstruction emerged as the standard of care and preferred method of urinary diversion for patients undergoing radical cystectomy (RC) for bladder cancer in referral centres from Western countries [1]. Several reports demonstrated the long-term safety of the procedure in terms of oncologic outcome [1–4], metabolism consequences [1,5], and renal function preservation [1,2,6]. With regard to functional outcome following orthotopic bladder reconstruction, 75–95% of patients were reported to be continent during the day [1,5,7,9–14] and 50–90% during the night [1,5,8–14], while 3–35% of patients used clean intermittent catheterisation (CIC) to void the neobladder [5,8,10,11,13]. Finally, although erectile function is not related to urinary diversion, 10–30% of patients reported erections after cystectomy [5,15,16]. Despite the large number of available papers, most of these data consider only three neobladder types—hemiKock, Stude, and Hautmann [1]—and none of the available surgical series use validated questionnaires to evaluate functional outcomes. Patient self-completed questionnaires, indeed, represent the most important clinical tool for evaluating symptom impact and treatment benefit from a patient perspective [17]. Validated questionnaires provide a method for a standardised collection of data and an objective assessment of a subjective phenomenon, limiting the impact of the clinicians’ assessments of patients’ outcomes and heterogeneity among the different series. Several validated questionnaires are available for evaluating lower urinary tract symptoms (LUTS), urinary continence, and erectile function, including the American Urological Association Symptom Index (AUA-SI) [18], the International Consultation on Incontinence Questionnaire– Urinary Incontinence Short Form (ICIQ-UI SF) [19], and the five-item version of the International Index Erectile Function (IIEF-5) [20]. Our usual choice for urinary diversion after RC is the vescica ileale Padovana (VIP) neobladder, an original technique that our group proposed in 1990 [21] but whose functional results have not been reported. The purpose of the present study was to evaluate the midterm functional results in a contemporary series of patients undergoing RC and VIP orthotopic ileal neobladder for transitional cell carcinoma (TCC) of the bladder by applying a set of validated questionnaires.
contraindications were preoperative stress urinary incontinence; significant patient comorbidity; and patients unwilling, unfit, or—in the surgeon’s judgment—unable to comply with the voiding pattern required by the reservoir. Ten different surgeons performed all the procedures. All patients underwent pelvic-iliac lymphadenectomy with en bloc RC as described by Skinner and Lieskovsky [23]. Preservation of the neurovascular bundles was not routinely performed. With regard to orthotopic ileal neobladder, all patients underwent reconstruction of the neobladder using the VIP technique [21,24]. Briefly, a portion of terminal ileum 40 cm long is isolated approximately 20 cm proximal to the ileocecal valve and opened along the antimesenteric border. The distal 10-cm segment is intended to constitute a funnel for ileal-urethral anastomosis, while the proximal 30-cm segment of ileum is folded in a jellyroll fashion to produce a posterior plate. The pouch is then closed anteriorly. Patients did not undergo neoadjuvant chemotherapy, although adjuvant chemotherapy was proposed in cases of pathologic lymph node involvement. Patients with neobladder were instructed to void every 3 h during the day through simultaneous relaxation of the pelvic floor musculature and the raising of intra-abdominal pressure with a Valsalva manoeuvre. Moreover, they were encouraged to limit fluid intake after the evening meal, to void before going to sleep, and to set an alarm clock to awaken and void once or twice during the night. Patient performance status (PS) was evaluated according to the Eastern Cooperative Oncology Group (ECOG) classification [25], while patient comorbidity was assessed by the Charlson Comorbidity Index (CCI) [26]. American Society of Anaesthesiologists (ASA) score was used to estimate perioperative risk [27]. Clinical staging was reported according to the 2002 TNM system [28]. Median patient follow-up was 44 mo (interquartile range [IQR]: 30–58). At follow-up, 68 patients (34%) experienced cancer-related death, while 14 patients (7%) died of other causes. Six patients (3%) were alive with disease progression, and 113 patients (56%) were alive and disease free. The patients alive and disease free were evaluated in a cross-sectional fashion, being invited during follow-up visits to self-fill the Italian validated translations of the AUA-SI [18], ICIQ-UI SF [19], and IIEF-5 [20] questionnaires. Moreover, patients were asked how many liners they used during both the day and night and about the use of proerectogenic drugs. LUTS were graded in mild (AUA-SI 7), moderate (AUA-SI 8–19), and severe (AUA-SI > 20) according to the overall score. Moreover, storage (questions 2, 4, and 7) and voiding (questions 1, 3, 5, and 6) subscores were provided [18]. The severity of urinary incontinence was graded as suggested by Klovning et al [29]. Specifically, patients with a ICIQ-UI SF score of 0 were considered fully continent; patients with scores ranging from 1 to 5, 6 to 12, 13 to 18, and 19 to 21 defined slight, moderate, severe, and very severe incontinence, respectively. Postoperative erectile dysfunction was graded as mild (IIEF-5 scores 22–25), mild to moderate (IIEF-5 scores 17–21), moderate (IIEF-5 scores 11–16), and severe (IIEF-5 scores 6–10) as suggested by Cappelleri et al [20]. All procedures were in accordance with the ethical standards established in our country.
2.
Materials and methods
Internal review board approval was not required for such a nonexperimental study.
From January 2002 to December 2006, 201 patients underwent RC and orthotopic ileal neobladder for nonmetastatic bladder TCC at the
2.1.
Statistical analysis
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Italy. The indications for RC included tumour invasion
Continuous, normally distributed variables were reported as the
of the muscularis propria; high-grade invasive bladder tumours or
mean value standard deviation (SD). Continuous non-normal vari-
carcinoma in situ; or recurrent, multifocal, non–muscle-invasive disease
ables were presented as the median values and IQR. Fisher exact test and
refractory to intravesical immunotherapy [22]. Indications for orthotopic
the Pearson x2 test were used to compare the distribution of categoric
ileal neobladder included absence of locally advanced disease, absence of
variables. Mann-Whitney U and Kruskal-Wallis H tests were used to
disease at the level of the bladder neck and prostatic urethra, normal renal
compare two or more independent samples. Binary regression was used
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<0.05 was considered statistically significant. All data were analysed
Table 1 – Clinical and pathologic characteristics of 113 evaluated patients
using the Statistical Package for the Social Sciences v.16.0 (SPSS,
Variables
for multivariable analysis. For all statistical analyses, a two-sided p value
Cases
Chicago, IL, USA).
3.
Results
Table 1 summarises the clinical and pathologic characteristics of the 113 analysed patients. 3.1.
Lower urinary tract symptoms
Sixteen patients (13%) were on CIC. The median AUA-SI of the 97 patients who voided spontaneously was 9 (IQR: 4.5–16). Specifically, the median storage subscore was 3 (IQR: 1–4), while the median voiding subscore was 5.5 (IQR: 0–12). Finally, 47 patients (48.5%) had mild, 39 (40.2%) moderate, and 11 (11.3%) severe LUTS, respectively. Table 2 summarises all the findings of the AUA-SI. Compared to those voiding spontaneously, the patients needing CIC had significantly higher body mass index (BMI) scores (26.1 2.8 vs 29 2; p = 0.016), worse ECOG PS ( p = 0.018), and a higher ASA class (0.031). On multivariable analysis, when excluding ECOG PS because of colinearity with ASA class, both ASA class (OR: 9.0; p = 0.03) and BMI (OR: 1.5; p = 0.023) were independent predictors of the need for CIC (Table 3). LUTS severity, indeed, was significantly associated with patient age at the time of surgery ( p = 0.007) and CCI ( p = 0.034), with patients who reported moderate to severe LUTS being younger and having lower CCI scores compared to those with mild LUTS (Table 4). On multivariable analysis, only patient age retained an independent predictive value (OR: 0.920; p = 0.01; Table 4).
Gender, no. (%): Male Female BMI, mean SD
26.4 2.9
ECOG PS, no. (%): 0 1 2
67 (59) 36 (32) 10 (9)
ASA class, no. (%): I II III
15 (13) 67 (59) 31 (28)
CCI, median (IQR) Clinical T stage: T1 T2 T3 Clinical N stage, no. (%): N0 N+ Pathologic T stage, no. (%): T1 T2 T3 T4 Pathologic N stage, no. (%): N0 N1
Urinary incontinence
The median ICIQ-UI SF score was 6 (IQR: 3–10). On the whole, 20 patients (17.7%) were fully continent, while 36 (31.9%), 40 (35.4%), and 17 (15%) patients had slight, moderate, and severe incontinence, respectively. Seventyseven (68%) of our patients used no pad, 26 (23%) used a safety pad for occasional leakage, and 10 (9%) used one or more pads during the day. During the night, 26 (23%), 70 (62%), and 17 (15%) patients used no pad, a safety pad for occasional leakage, or one pad or more, respectively. In general, those using protection reported using a median number of one pad (IQR: 1–1), during both the day and the night. According to question 3 of the ICIQ-UI SF, the overall interference of urinary incontinence on patients’ everyday life was limited (median: 1.5; IQR: 0–5). According to question 4 on the ICIQ-UI SF, 59% of the patients leaked when asleep. Table 5 summarises all the findings of the ICIQ-UI SF questionnaire. None of the preoperative variables turned out to be predictive of the presence of any grade of or severe urinary incontinence at follow-up, even in univariable analysis (Table 6).
0 (0–1)
57 (50) 55 (49) 1 (1)
107 (95) 6 (5)
66 25 15 7
(58) (22) (13) (7)
104 (92) 9 (8)
SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; ASA = American Society of Anaesthesiologists; CCI = Charlson Comorbidity Index; IQR = interquartile range.
3.3. 3.2.
105 (92.9) 8 (7.1)
Erectile function
At follow-up, only 96 out of 105 patients filled out the IIEF-5 questionnaire. The median IIEF-5 score of those patients was 5 (IQR: 5–17.7). Considering all patients who did not fill the questionnaires impotent, 7 men (6.6%) had mild to moderate erectile dysfunction, and 18 men (17.1%) had mild erectile dysfunction, 10 with the assistance of phosphodiesterase type 5 inhibitors. 4.
Discussion
The VIP neobladder is an original technique for bladder substitution following RC developed in our centre in the late 1980s and reported for the first time by our group in 1990 [21]. To date, VIP is the second most commonly used neobladder in Italy, being used by 50 out of the 157 urological centres involved in a specific survey performed in 2006 [30]. In the present study, we used validated questionnaires to evaluate LUTS, urinary continence, and erectile function after RC with VIP neobladder. At a median follow-up of 44 mo, about 90% of the spontaneously voiding patients reported mild or moderate LUTS, although 13% needed CIC.
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Table 2 – Detailed data of the American Urological Association Symptom Index in 97 patients voiding spontaneously AUA-SI
Score, median (IQR)
Q1: Over the last month or so, how often have you had a sensation of not emptying your bladder completely after you finished urinating? Q2: During the last month or so, how often have you had to urinate again less than 2 hours after you finished urinating? Q3: During the last month or so, how often have you stopped and started again several times when you urinated? Q4: During the last month or so, how often have you found it difficult to postpone urination? Q5: During the last month or so, how often have you had a weak urinary stream? Q6: During the last month or so, how often have you had to push or strain to begin urination? Q7: During the last month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning? If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? Storage subscore (questions 2, 4, and 7) Voiding subscore (questions 1, 3, 5, and 6) Overall score
0 (0–1) 0 2 0 0 2 2
(0–1) (0–5) (0–0) (0–3) (0–5) (1–3)
0 (0–0) 3 (1–4) 5.5 (0–12) 9 (4.5–16)
Severity of LUTS, no. (%): Mild Moderate Severe
47 (48.5) 39 (40.2) 11(11.3)
AUA-SI = American Urological Association Symptom Index; IQR = interquartile range; LUTS = lower urinary tract symptoms.
Table 3 – Preoperative predictors of the need of clean intermittent catheterisation Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
CIC
Univariable analysis p value
No (n = 97)
Yes (n = 16)
90 (93) 61.7 8.9 26.1 2.8 48 (55) 0 (0–1) 59 (68) 47 (48) 94 (97)
14 (93) 65.5 7 29 2 5 (36) 1 (0–2) 6 (42) 7 (47) 14 (93)
Multivariable analysis OR; 95% CI
1 0.158 0.016 0.018 0.316 0.031 0.132 0.445
– – 1.5; 1.06–2.15 – – 9.0; 1.1–71-8 – –
p value – – 0.023 – – 0.03 – –
CIC = clean intermittent catheterisation; OR = odds ratio; CI = confidence interval; SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
Table 4 – Preoperative predictors of postoperative lower urinary tract symptoms severity Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
LUTS
Univariable analysis p values
Mild (n = 47)
Moderate (n = 39)
Severe (n = 11)
43 (95) 65 7.3 25.8 2.2 18 (51) 1 (0–2) 26 (74) 22 (47) 46 (98)
37 (95) 59.1 9.7 26.3 3.3 23 (72) 0 (0–0) 26 (81) 20 (51) 38 (97)
10 (91) 57.6 7.7 25.8 3.1 7 (78) 0 (0–1) 7 (78) 5 (45) 10 (91)
Multivariable analysis OR; 95% CI
0.807 0.007 0.863 0.282 0.034 0.404 0.745 0.632
– 0.92; 0.86–0.98 – – 0.72; 0.46–1.18 – – –
p value – 0.01 – – 0.15 – – –
LUTS = lower urinary tract symptoms; OR = odds ratio; CI = confidence interval; SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
Considering as continent those patients using no pad or a safety pad, about 90% and 80% of our patients achieved daytime and night-time continence, respectively. However, based on the strict ICIQ-UI SF criteria, <20% of the patients were fully continent, although most of the patients reported incontinence of slight to moderate severity. Finally, roughly 25% of the male patients were potent. Some clinical characteristics of the patients (mainly age, BMI, ASA class,
and CCI score) were predictive of the need of CIC and LUTS severity. Our 13% of CIC is similar to those scores previously reported in the literature, where 3–35% of the patients used CIC to void the neobladder [5,8,10,11,13]. The wide range of proportion of patients in CIC might reflect differences in surgical technique, patient characteristics, follow-up duration, and so on. However, our finding that BMI was
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Table 5 – Detailed data of the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form questionnaire in our cohort of patients ICIQ-UI SF
Cases, no. (%)
Q1: How often do you leak urine? Never About once a week or less often 2 or 3 times a week About once a day Several times a day All the time
24 (21.2) 35 (31) 27 (23.9) 15 (13.3) 9 (8) 3 (2.7)
Q2: How much urine do you usually leak? None A small amount A moderate amount A large amount
22 (19.5) 75 (67.2) 13 (11.5) 2 (1.8)
Q3: Overall, how much does leaking urine interfere with your everyday life? median (IQR) 1.5 (0–5) Q4: When does urine leak? Never Leaks before you can get to the toilet Leaks when you cough or sneeze Leaks when you are asleep Leaks when you are physically active/exercising Leaks when you have finished urinating and are dressed Leaks for no obvious reason Leaks all the time Overall score, median (IQR)
16 (14.1) 5 (4.4) 17 (15) 67 (59.3) 8 (7.1) 0 (0) 13 (11.5) 2 (1.8) 6 (3–10)
Severity of the incontinence: Fully continent (score 0) Slight incontinence (score 1–5) Moderate incontinence (score 6–12) Severe incontinence (score 13–18)
20 36 40 17
(17.7) (31.9) (35.4) (15)
ICIQ-UI SF = International Consultation on Incontinence Questionnaire– Urinary Incontinence Short Form; IQR = interquartile range.
significantly associated with the need for CIC in multivariable analysis might reconfirm that the funnel-shaped outlet could increase the risk of obstruction resulting from kinking in obese patients, as suggested by Studer et al [5]. Likely, a modification of the VIP surgical technique should be tested in order to attempt to reduce the rate of CIC in such patients. Because of the specific selection of questionnaires for evaluating functional outcomes, most of our data are not
comparable to those previously reported in other surgical series. With regard to LUTS, Madersbacher et al evaluated a series of 83 patients at a median follow-up of 95 mo with the use of frequency–volume charts, reporting a mean of 4.3 0.5 micturitions during the day and 2.0 0.7 micturitions during the night [31]. Although obtained using a different tool, the median storage subscore of the AUA-SI in our series reconfirms similar results. Our finding that age was an independent predictor of LUTS severity, with younger patients more commonly experiencing severe symptoms, was original and difficult to explain. The inability to correlate these figures with a preoperative baseline evaluation, during which older patients were more likely to report worse symptoms, prevents us from drawing definitive conclusions on this issue, which, indeed, can be identified only in prospective studies. Regarding urinary continence, the published series with longer follow-up durations reported daytime and nighttime continence rates ranging from 75% to 95% [1,5,7,9–14] and from 50% to 90% [1,5,8–14], respectively. All these studies reported as continent those patients not using any pad or condom or, in some series, those patients using a safety pad for occasional leakage, as well. Applying these two criteria, about 69% and 91% of our patients might be considered continent during the day and 25% and 85% during the night, respectively. The data from the ICIQ-UI SF, indeed, showed that by applying standardised, validated, patient-reported criteria, significantly lower figures can be obtained, with perfect continence being rare—definitively more realistic data patients should be aware of before surgery. None of the analysed clinical variables turned out to be significantly associated with continence recovery at follow-up, likely because of the small sample size. Finally, about 23% of our patients reported having mild to moderate or mild erectile dysfunction. The data are similar to those previously reported in the literature for RC, where 10–30% of patients are potent [5,15,16]. Specifically, Zippe et al reported on a small series of 49 patients, 14% of them being potent, with a mean IIEF-5 score of 16.6 4.9 at a mean follow-up of 44.4 mo [16]. Kessler et al, evaluating a series of 331 patients in which unilateral or bilateral preservation of the neurovascular bundles was attempted in 65.9% and 11.5% of the patients, respectively, reported 2-yr potency rates as high as 30% and 60% in case of the unilateral and bilateral nerve-sparing procedure, respectively [15]. Such
Table 6 – Preoperative prognostic factors predictive of any grade of and severe incontinence Variable
Male gender, no. (%) Age, mean SD BMI, mean SD ECOG PS 0, no. (%) CCI, median (IQR) ASA class I–II, no. (%) cT2 tumours, no. (%) cN0 tumours, no. (%)
Fully continent patients (n = 20)
Patients with any grade of incontinence (n = 93)
p values
Patients with severe incontinence (n = 17)
19 (95) 62.5 4 26.3 3.9 10 (50) 2 (1–3) 14 (70) 13 (65) 18 (90)
86 (92) 61.7 9.5 26.4 2.3 44 (62) 2 (1–4) 52 (73) 42 (45) 91 (98)
1 0.810 0.595 0.621 0.297 0.879 0.445 0.143
15 61.4 10 26.7 2.8 9 (53) 2 (1–5) 12 (70) 9 (53) 16 (94)
p values
0.414 0.908 0.631 0.916 0.719 0.374 0.549 0.484
SD = standard deviation; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; PS = performance status; CCI = Charlson Comorbidity Index; IQR = interquartile range; ASA = American Society of Anaesthesiologists.
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a finding was surprising, considering that neurovascular bundle preservation was not routinely performed in our patients. Considering the young patient age, the lack of comorbidity, and the long follow-up, it might be hypothesised that nerve regeneration may have occurred following partial preservation and also that the presence of interindividual anatomic variations in the distribution of the nerve supply might have been present. However, the study design and the lack of other data at long-term follow-up from other series do not allow us to provide definitive conclusions on these issues. The major strengths of the present study are the use of validated questionnaires to evaluate functional outcomes and the longer follow-up. Because of the relatively long median follow-up, those patients are at low risk of cancerrelated death; consequently, those functional data can likely be considered those of cancer survivors after cystectomy. On the whole, these data provide an accurate picture of the midterm functional outcomes of VIP orthotopic neobladder from a strict patient perspective and are of interest for preoperative patient counselling as well as for comparisons of the performance of different neobladders when similar validated tools will be applied in other series. There are some limitations to our study, the largest of which is the limitation inherent to cross-sectional analyses, which did not allow us to evaluate preoperative functional outcomes and their impact on status at follow-up. In addition, the sample size was not particularly large, mainly because of cancer-related mortality. Consequently, some of our statistical analyses were underpowered. A third limitation was the large number of surgeons performing neobladder procedures in our series, which could have affected the study results. Fourth, because of the lack of specific questionnaires developed to assess urinary continence following orthotopic neobladder, we selected to use the ICIQ-UI SF because of the robust psychometric properties of the questionnaire and the extensive number of studies using such a tool in the evaluation of patients with different types of urinary incontinence [17]. However, the questionnaire had never been used in this clinical setting. Finally, the low number of female patients and the lack of validated Italian translations of questionnaires evaluating female sexual dysfunction prevent us from assessing that issue. 5.
Conclusions
Author contributions: Vincenzo Ficarra had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Novara, Ficarra, Artibani. Acquisition of data: Minja, De Marco. Analysis and interpretation of data: Novara. Drafting of the manuscript: Novara. Critical revision of the manuscript for important intellectual content: Ficarra, De Marco, Artibani. Statistical analysis: Novara. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Artibani. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.
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