Peri-operative, Functional, Quality of Life, and Oncological Outcomes After Robot-Assisted Radical Cystectomy and Intra-corporeal Orthotopic Ileal Neobladder—Our Experience

Abstract

Robot-assisted radical cystectomy (RARC) and intracorporeal orthotopic neobladder (OINB) is technically a challenging surgery due to the involvement of prolonged console time and higher level of surgical skills. Therefore, standardizing technique and testament of good functional and oncological outcomes is required to increase its acceptance among surgeons. We report our experience of RARC with OINB and analyze the perioperative, functional, quality of life, and survival outcomes. Single surgeon experience of over 22 OINB after RARC is done, which includes 21 male and one female patients, was done retrospectively. Modified Karolinska Studer technique of neobladder creation was followed. Intraoperative findings, post-operative complications, and follow-up information were recorded for analysis. The patients’ median age was 50.5 years (IQR, 41.25–55.50), and the median follow-up period was 45.5 months (IQR, 26.75–68). Median console time was 447.5 min (IQR, 347.5–500), blood loss was 225 ml (IQR, 200–250), and hospital stay was 12 days (IQR, 11–15). Most of the complications were Clavien-Dindo grades I and II. Longer surgery time and more complications were noted in the first 10 cases compared to the next 12 cases. Day and night-time urinary continence is 95% and 77% at 12 months, respectively. Two patients died of disease, and overall survival at 5 years was 84%. Our experience supports OINB as a feasible option after RCIC with acceptable complications, good functional and survival outcomes, with better quality of life. With experience, surgical morbidity and operative time decrease. This surgery should be undertaken after gaining experience with an intracorporeal ileal conduit and has a steep learning curve.

Introduction

Open radical cystectomy (RC) with bilateral pelvic lymph node dissection (PLND) and urinary diversion (UD) is the gold standard in the treatment of non-metastatic muscle-invasive bladder cancer (MIBC) and selected cases of high-risk non-muscle-invasive bladder cancer (NMIBC) [1]. Ileal conduit urinary diversion is widely practiced; however, orthotopic neobladder remains the more acceptable choice in selected patients in terms of quality of life, maintaining body image, and normal voiding [2].

With added advantages of robotic technology, many centers have rapidly adopted robotic radical cystectomy and urinary diversion. Studies have shown equivalent survival outcomes after robot-assisted radical cystectomy (RARC) compared to open surgery [3]. Although the robotic extracorporeal urinary diversion (ECUD) is the preferred choice to many surgeons, intra-corporeal urinary diversion (ICUD) has few definite advantages like reduced intra-operative evaporative fluid loss, lesser blood loss, faster recovery of bowel movement, reduced post-operative hospital stay [4].

Initial experience of ICUD with neobladder in reported studies was not encouraging due to the complexity of the procedure, relatively long operative time, and an increased incidence of surgical morbidity. There is a need to standardize the surgical technique to minimize complications and enhance functional and survival outcomes. We present our experience of RARC with orthotopic intra-corporeal neobladder (OINB) and analyze the peri-operative, functional, quality of life, and oncological outcomes.

Materials and Methods

We performed 223 standard RARC with extended PLND and UD from May 2012 to March 2020 in our institute, out of which 22 patients (10%) had orthotopic ileal neobladder. A combined intra- and extracorporeal approach was made in the first two orthotopic neobladder cases, and a complete intracorporeal approach was performed in others. The choice of neobladder UD was based on tumor characteristics, age, renal function status, and patient acceptance. Patients with previous extensive abdominal surgery, poor cardiopulmonary function, and uncontrolled glaucoma were excluded. Surgery was done using the Da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA). Patients’ baseline demographic details, peri-operative details, pathological information, functional outcomes, quality of life, and oncological data were recorded and analyzed retrospectively.

NCCN follow-up protocol was followed; urine cytology, blood investigations with kidney function test, chest x-ray, and CT urogram were done every 3–6 months. Functional assessment included history about continence, voiding pattern, need for clean self-intermittent catheterization (CSIC), ultrasound abdomen with estimation of post-void residual (PVR) urine during each follow-up. Urodynamic study (UDS) was done at 6 months. Bladder Utility Symptom Scale (BUSS), a reliable self-assessment tool for measuring overall health-related quality of life (HRQOL) after RARC-OINB, was completed by patients during the last follow-up or via e-mail. As this was a retrospective study, an informed consent for inclusion in the study from participants was not taken. However, all the participants provided written informed consent for undergoing surgery, and we adhered to the principles of the Helsinki Declaration, 1964 (amended in 2013). We confirm the availability and access to all the original data reported in this study.

Currently, we are performing the Karolinska-modified Studer technique for OINB with one modification. In brief, our technique involved the use of 55 cm of distal ileum (30 cm proximal to ileocecal junction). The first and most crucial step was performing the urethro-ileal anastomosis before bowel isolation (which helps identify the most dependent segment) using a 4–0 V-loc suture. Then, ileum was isolated, and remaining bowel continuity was achieved with Endo-GIA staplers. Forty centimeters of distal ileum was detubularized (Fig. 1A), and ureteric anastomosis was done to proximal 10 cm of tubular ileum. The posterior plate suturing was done by using a 3–0 stratafix suture (Fig. 1B). Due to a narrow pelvis and restricted working space, we sutured the neobladder’s anterior wall proximally for 4–5 cm from the urethral end to create a funnel-shaped neobladder (modification of Karolinska technique) (Fig. 1C). The anterior wall was then folded to create a conical shape Studer neobladder. Bricker’s technique was used for uretero-ileal anastomosis over ureteral stents, which were exteriorized, and suprapubic tube was kept (Fig. 1D).

Fig. 1.

A Fifty-five centimeters of distal ileum (30 cm proximal from ileo-cecal junction) is isolated, urethro-ileal anastomosis done, and 40 cm of distal ileum is detubularized. B The posterior plate of distal detubularized ileum is sutured. C Anterior wall of neobladder is closed longitudinally for 4–5 cm proximally from the urethral end to create a funnel shape. D The anterior wall is double folded to create a conical-shaped Studer neobladder. Uretero-ileal anastomosis is done by Bricker’s technique. (✻Urethro-ileal anastomosis. †Side to side anastomosis by Endo GIA staplers. §Uretero-ileal anastomosis)

Statistical Analysis

We used SPSS Statistics v20.0 (IBM Corp, NY, USA) software for the statistical analysis. Descriptive statistics, including mean, median, range, inter quartile range (IQR), and statistical significance, were used to report scale and categorical data. The Student t-test was used to compare the means of values comparing the first ten and next 12 cases of the neobladder. A p-value of < 0.05 was considered significant.

Results

Among 22 patients who had orthotopic neobladder, the first two patients underwent combined intra- and extracorporeal techniques where Studer neobladder was created extracorporeally and robot-assisted urethra-neobladder anastomosis was done after redocking of robot. The remaining 20 patients had total intracorporeal Studer neobladder (four patients) or modified Karolinska Studer neobladder (16 patients).

The patients’ median age was 50.5 years (IQR, 41.25–55.50), with a median follow-up period of 45.5 months (IQR, 26.75–68). There were 21 males and one female patient. She underwent genital organ-preserving (uterus and ovary) cystectomy and OINB. Six patients (27%) had a history of smoking or tobacco chewing. Indications for surgery were MIBC in 21 patients and BCG-resistant high-grade NMIBC in one patient. Neoadjuvant chemotherapy was advised in all MIBC patients; however, only four patients (18%) received four cycles of gemicitabine and cisplatin. EORTC risk stratification was zero in 19 patients and one in three patients. Median BMI was 25.97 (IQR, 24.11–26.23), median hemoglobin level was 11.65 gm% (IQR, 10.42–13.25), and median serum creatinine was 0.81 mg% (IQR, 0.65–0.92).

Median console time for surgery was 447.5 min (IQR, 347.5–500). Median blood loss was 225 ml (IQR, 200–250), and one patient needed a blood transfusion in the post-operative period. There were no intraoperative complications, and there was no need for conversion to open. The mean ICU stay was 1.4 days (range, 0–3 days), while the median hospital stay was 12 days (IQR, 11–15). Patients were started on an oral diet after a median time of four days (IQR, 3–6). Total parenteral nutrition (TPN) was supplemented for 3–5 days in five patients due to delay in the starting of oral feeds. (Table 1).

Table 1.

Baseline demographic details, peri-operative findings, and postoperative complications of carcinoma bladder patients treated with robot-assisted radical cystectomy (RARC) and orthotopic intracorporeal neobladder (n—number of patients, IQR—inter quartile range)

Variable	Value
Median age, years(IQR)	50.5 (41.25–55.50)
Gender, n = male, female	21,1
Median BMI, kg/m2 (IQR)	25.97 (24.11–26.23)
Median hemoglobin level, gm% (IQR)	11.65 (10.42–13.25)
Median serum creatinine level, mg% (IQR)	0.81 (0.65–0.92)
Median console time, min (IQR)	447.5 (347.5–500)
Median blood loss, ml (IQR)	225 (200–250)
Mean ICU stay, days (Range)	1.4 (0–3)
Median time to oral intake, days (IQR)	4 (3–6)
Median hospital stay, days (IQR)	12 (11–15)
Clavien-Dindo complications, n (%) All grade Grade I Grade II Grade IIIa	13 (59%) 4 (18.2%) 6 (27.2%) 3 (13.6%)

All grade 30-day Clavien-Dindo post-operative complications were seen in 13 patients (59%). Four patients had grade I (18.2%), six had grade II (27.2%), and three patients had grade IIIa (13.6%) complications. One patient had a urinary leak (IIIa), which was managed by pigtail pelvic drainage and bilateral percutaneous nephrostomy (PCN). The other two patients (grade IIIa) required pigtail insertion for infected lymphocele. There was no 30-day mortality in the entire cohort. Long-term complications included one patient developing infected lymphocele after 2 years requiring pigtail drainage, and another patient had subacute intestinal obstruction after 3 years, which was managed conservatively.

The first case of OINB was performed after gaining experience of performing 20 intracorporeal ileal conduits. We compared operative time, hospital stay, and complications in the first 10 cases of OINB to the next 12 cases to assess the learning curve. Median console time was 518 and 391 min (p = 0.009); all grade complications were seen in 8 (80%) and 5 patients (42%) (p = 0.05) among first 10 and next 12 cases respectively. There was no difference in blood loss (225 vs. 230, p = 0.805) and the hospital stay. The protocol followed for stents and catheter management is as follows: ureteric catheters were blocked on day 8 and removed on the 10th day, suprapubic tube (SPT) was blocked, and per urethral catheter was removed on the 14th day. SPT was removed between 18 and 21 days after checking for post-void residue (PVR). Cystogram was not done routinely except in patients with neobladder leak. Pelvic floor exercise and timed voiding pattern were taught to all patients.

Final histopathology reports showed pT₀ in 3 (13.6%), pT₁ in 1 (4.5%), pT₂ in 10 (45.4%), pT₃ in 8 patients (36.4%), pN₀ in 18 (81.8%), pN₁ in 2 (9.1%), and pN₂ in 2 (9.1%) and surgical margin was negative in all patients. Incidental foci of prostate adenocarcinoma with Gleason score 3 + 3 = 6 were seen in one patient. The mean number of lymph nodes dissected was 20 (range, 13–32), and three with positive lymph nodes received adjuvant chemotherapy. During follow-up, one patient had neobladder stone formation, which was removed endoscopically. Another patient developed urethra-neobladder anastomotic stricture after 1 year and was treated with holmium laser incision and presently doing well with regular CSIC. CSIC was required in 2 patients (9.1%), and the remaining 20 patients are voiding urine normally supported by abdominal compression.

Functional analysis included voiding pattern assessed by uroflowmetry, day and night time continence rates, PVR, CSIC rate, and repeated urinary tract infection incidence. The average flow rate was 18 ml/s on uroflowmetry, and the average PVR was 85 ml (20–200 ml) on ultrasound examination. Six patients underwent UDS, which showed a mean capacity of 550 ml (380–900 ml), normal compliance 32 ml/cm of H₂O, with a mean PVR of 115 ml. (50–160 ml). Daytime continence was 78% at 6 months and 95% at 12 months; one patient uses 1–2 safety pads per day. Night-time continence was 77% at 12 months. Serum creatinine was checked during follow-up, which was in the normal range in all patients (0.3–1.1 mg %). Upper tract deterioration was seen in one patient’s renal unit, which was due to ureteric anastomotic stricture, which was managed by balloon dilatation.

Twelve patients completed and submitted the filled BUSS questionnaire. Mean BUSS score was 88 (range, 70–98) at the last follow-up. Two patients were lost to follow-up after 34 and 55 months. Overall survival at 5 years is 84%, and at 7 years is 72% among the entire group. Four patients died due to disease recurrence treated with second-line chemotherapy, and the other two patients died due to other causes (Fig. 2).

Fig. 2.

Estimated probability with Kaplan–Meier analysis of overall survival rate in patients of carcinoma bladder treated with robot-assisted radical cystectomy (RARC) and orthotopic intracorporeal neobladder

Discussion

Bladder cancer is the second most common genitourinary cancer. MIBC accounts for 25% of cases; radical cystectomy and urinary diversion with ileal conduit are most commonly performed in these patients, and neobladder is more commonly preferred. Camey and Le Duc successfully performed the first open orthotopic neobladder in 1979 [5]. With invent of minimal invasive techniques, Gill was the first to perform laparoscopic intracorporeal ileal conduit in 2000 and orthotopic Studer neobladder in 2002 [6, 7]. With a step forward, Menon was the first to describe robot-assisted radical cystectomy with extracorporeal UD [8]. Creating total intracorporeal urinary diversion is challenging. Beecken, for the first time, performed total intracorporeal Hautman neobladder on the robotic platform in 2003 [9]. The robotic approach’s advantages include less blood loss, early recovery of bowel function, and less pain.

Due to technical difficulty and reported higher complication rates during the learning curve with ICUD, ECUD with either ileal conduit or neobladder is generally preferred by most surgeons [10]. Adequate patient selection remains the key for OINB to reduce peri-operative or post-operative morbidity. Motivated patients less than 65, with fewer comorbidities (< 3 Charlson comorbidity index), lower BMI, and lower ASA score [11], are suitable for neobladder. With the experience of robotic pelvic surgeries, ICUD is more frequently performed in recent times. In fact, < 5% of RC patients underwent ICUD previously, but now up to 97% of patients in International Robotic Radical Cystectomy Consortium (IRCC) centers underwent ICUD, and 17% of them being neobladder [12]. We started performing RARC in 2012 and hereby present results of 22 OINB (10%) from total of 223 RARC, performed by a single surgeon at a tertiary health care institute till March 2020.

Different techniques have been described for the construction of orthotopic neobladder; most of them are done by detubularized ileum [13]. The ileum has advantages of more distensibility, large capacity, and low pressure and minimal metabolic consequences due to mucosal atrophy in the long run. The most extensive reported series of ICUD with ileal neobladder is by Karolinska Institute and the University of Southern California with 132 patients, where the modified Studer technique is used for the creation of ileal neobladder [14]. Few other techniques include Hautman’s pouch (W shaped), Vesicae-Ileale Padovana (VIP—circular shaped), pyramidal pouch, and Y pouch. We performed OINB with Studer neobladder in four patients and modified Karolinska Studer neobladder in 16 patients. We did minor modifications to the Karolinska technique where the anterior wall was closed for 4–5 cm before double folding the neobladder, and ureteric anastomosis was done by Bricker’s technique.

One of the limiting factors for ICUD with neobladder is the prolonged time involved in the procedure. RARC and PLND are well-standardized procedures. High-volume centers have an advantage of a step-wise reduction in operative time (OT) with increasing cases. We also noticed a similar trend as the median OT in our first ten and last 12 cases was 518 and 391 min respectively. A study by Beecken et al. demonstrated the operative time of 8.5h⁹; however, it was 7.5 to 12 h in other subsequent studies [15–18].

In the Karolinska group of 70 patients, minor complications of 17% and 11.4%, and significant complications of 31.4% and 18.5% were reported at 0 to 30 days and $>$ 30 days, respectively. The overall complication rate was 51.2%, of which the majority were infections [19]. In their study group of 132 patients, Desai et al. noted early and late complication rates of 47% and 27.3% with the commonest benign uretero-enteric stricture and hydroureteronephrosis [14]. In the present study, 30 days complications were noted in 13 patients (59%), out of which ten patients had minor complications (Clavien-Dindo grades I and II), and three patients (13.6%) had grade IIIa complications. Fontana et al. reported a 6% rate of stone formation in ileal neobladder constructed with titanium staples, which increased up to 9% in other studies [20, 21]. In our study, one case (4.5%) had stone formation in neobladder, and it was cleared by laser lithotripsy.

The functional outcomes of neobladder depend on the technique used for reconstruction. It should provide adequate capacity, low pressure, normal voiding, continence, and renal function preservation. Long-term functional outcomes after neobladder reconstruction are excellent in the literature, with > 90% achieving daytime continence at 1 year [22]. Simone et al., in their series of Padovana ileal neobladder, had 1-year day and night-time continence rates of 73.3% and 55.5%, respectively [23]. In the Karolinska series, reported by Tyritzis et al., 12-month day and night-time continence was 88% and 76% in men with a strict definition of no pad usage [24]. In our series, daytime continence was achieved in 78% and 95% at 6 months and 12 months. Seventy-seven percent of patients attained night-time continence by 12 months, which is comparable to literature.

Six patients underwent UDS examination in which the mean bladder capacity was 550 ml (380–900 ml) with normal compliance (32 ml/cm of H₂O). This result is comparable to data from the University of Southern California (USC) group in which total capacity was 514 ml (330–1001 ml) with normal compliance of 33 ml/cm of H₂0 but had a higher PVR of 268 ml [14]. During the current study period, PVR was 75 ml (20–110 ml). The need for CSIC was 11% in the USC group compared to 1.4% in Karolinska neobladder [14, 19]. In the current study, regular CSIC was required in two patients (9.1%); one patient had urethral anastomotic stricture developed after 1 year. None of the patients in the study group had deterioration of renal function during follow-up.

Measuring HRQOL in patients with bladder cancer after radical cystectomy is very complex, as it depends on varied factors like cancer biology, treatment followed, surgery-related. So BUSS fills a niche as it measures global HRQOL in 10 easy questions that assess overall health [24]. It is a self-assessment questionnaire of 10 questions and scored from 0 to 100. Mean BUSS was 88 (range 70–98) in our study, indicating good quality of life in patients after RC-OINB.

Survival outcomes mainly depend on the excisional component of the surgery and pathological stage of the disease. All the patients in our study had pathologically organ-confined disease with negative surgical margins. All patients underwent extended PLND, and the mean lymph nodes dissected were 20 (range, 14–32). Three patients had positive node disease who received adjuvant chemotherapy. These findings are comparable to literature with an average of 19–29 nodes dissected [14, 23, 25]. In our study, OS at 5 years is 84%, and at 7 years is 72%; two patients developed recurrences who were treated with systemic chemotherapy but died of the disease. IRCC data updated analysis of oncological outcomes with a median follow-up of 44 months has shown 5-year recurrence-free survival, cancer-specific survival, and OS of 67%, 75%, and 50%, respectively [26]. The present study’s limitation is that it is retrospective in nature and hence does not have complete data, especially on UDS. It is challenging to generalize outcomes due to less number of patients in the study cohort.

Conclusions

RARC and total intracorporeal orthotopic neobladder is feasible and gaining wide acceptance as an option to the open approach. However, this should be done in high-volume centers where intracorporeal diversion is made regularly. Our study highlights acceptable peri-operative outcomes, better long-term functional outcomes, quality of life, and survival outcomes. With experience, operative time, blood loss, and complications were notably less. However, the study has less number of patients and is retrospective in nature. Further prospective studies with more number of patients in multicentre involvement are needed to validate OINB further.

Data Availability

Data are with the corresponding author.

Declarations

Ethical Board Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Written Consent

Informed written consent for surgery was taken, but consent to be involved in study was not, as it was a retrospective study.

Conflict of Interest

The authors declare no competing interests.

Disclaimer

The authors are responsible for correctness of the statements provided in the manuscript.