Comparison of perioperative and oncological outcomes between extracorporeal and intracorporeal urinary diversion following laparoscopic radical cystectomy and robot-assisted radical cystectomy

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Comparison of perioperative and oncological outcomes between extracorporeal and intracorporeal urinary diversion following laparoscopic radical cystectomy and robot-assisted radical cystectomy

https://doi.org/10.21203/rs.3.rs-3635099/v1

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Background

This study aimed to compare oncological outcomes between intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) following radical cystectomy in Japan.

Methods

This retrospective study included 110 patients who underwent laparoscopic radical cystectomy (LRC) or robot-assisted radical cystectomy (RARC) from 2013 to 2023. Twenty-nine participants underwent LRC with ECUD, 40 participants underwent RARC with ECUD, and 32 participants underwent RARC with ICUD. Predictors of postoperative outcomes were evaluated using a Cox proportional hazards model. Recurrence-free survival (RFS) and overall survival (OS) were measured using the Kaplan-Meier method.

Results

Estimated RFS at 36 months for RARC with ICUD, RARC with ECUD and LRC with ECUD was 79.9% (95% CI 57.9–91.2), 52.5% (95% CI 31.1–70.1) and 62% (95% CI 40.7–77.5), respectively. Estimated OS at 36 months for RARC with ICUD, RARC with ECUD and LRC with ECUD was 87.1% (95% CI 54.4–96.9), 60.4% (95% CI 33.6–79.3) and 80.7% (95% CI 56.9–91.5), respectively.

Conclusions

There were no statistically significant differences in oncological outcomes between ECUD and ICUD based on surgical approach. Only pathological stage ≥ T3 and N positivity were common predictors of poor OS and RFS outcomes.

Bladder cancer・ Intracorporeal urinary diversion・ Extracorporeal urinary diversion・ Oncological outcome

The standard surgery for muscle-invasive bladder cancer (MIBC) is open total cystectomy [1]. However, open total cystectomy and urinary diversion are highly invasive procedures, and have a high rate of perioperative complications. Minimally invasive techniques, such as laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) have been widely used to address these issues [2].

RARC is reportedly associated with several perioperative benefits, such as reduced blood loss, reduced transfusion rates, shorter hospital stays, and fewer complications [3–8]. Consequently, this surgical technique has increased in popularity. Radical cystectomy requires a urinary diversion procedure, either as intra- or extracorporeal urinary diversion. Intracorporeal urinary diversion (ICUD) is known to be technically difficult due to the complexity of the anastomosis between the ileum and ureter in laparoscopic surgery, and has been reported to prolong operative time, increase the frequency of intestinal complications, and delay postoperative recovery compared to extracorporeal urinary diversion (ECUD) [9–13]. However, induction of robotic surgery has simplified the anastomotic technique in ICUD. ECUD, on the other hand, requires a minilaparotomy incision for bowel manipulation and reconstruction.

Tan et al. reported that the learning curve for RARC + ECUD and RARC + ICUD requires performance of about 30 cases [14]. Teoh et al. analyzed perioperative outcomes between ECUD and ICUD in 556 RARC cases from 2007 to 2020 [15]. In their study, ICUD was performed in 55.2% and ECUD in 44.8% of cases, with ICUD cases showing less blood loss and shorter hospital stays than ECUD cases.

However, although there have been some reports comparing perioperative outcomes between ICUD and ECUD, only few reports have focused on oncological recurrence-free survival (RFS) and overall survival (OS) between ICUD and ECUD. Therefore, we retrospectively compared the oncological outcomes between ICUD and ECUD in real-world clinical practice in Japan.

1. Patients’ characteristics

MIBC cases treated with LRC or RARC from 2013 to 2023 at Kochi Medical School were included in this analysis. The Institutional Review Board of Kochi University Medical School approved this study (approval no. 2023-62) and waived the need for informed consent. Data were obtained from all patients who completed a general consent form based on the opt-out policy at Kochi Medical School. Patients’ demographic data, surgical parameters, pathological results and oncological outcomes were obtained from our database. The baseline characteristics included age, gender, smoking, neoadjuvant chemotherapy (NAC), pathological T stage, pathological N stage, surgical margin status, lymphovascular invasion status and adjuvant chemotherapy. The perioperative parameters were total cystectomy time (including lymph node dissection), urinary diversion time, perioperative blood transfusion, length of hospital stay, and occurrence of any complications within 30 days. Postoperative laboratory tests included serum white blood cell (WBC) count, C-reactive protein (CRP) and hemoglobin (Hb) levels. Total cystectomy time was defined as the time from the start of pneumoperitoneum to the end of lymph node dissection. Urinary diversion time was defined from the observation of the ileum to the end of surgery.

2. Perioperative management protocol

Basically, a total of two cycles of NAC based on platinum drugs was administrated. NAC was not administrated to patients older than 80 years or with impaired renal function, in order to avoid chemotherapy-related toxicity. Patients were made to ambulate as much as possible the day after surgery. Fluid intake was basically started on the third postoperative day, and food intake was started on the fourth postoperative day. Modifications to this protocol were made, as appropriate, according to the patient' s symptoms and the surgeon' s judgment.

3. Surgical procedure

a. Radical cystectomy technique

At Kochi Medical School, performance of LRC with ECUD commenced from 2013; RARC with ECUD started from 2018; and RARC with ICUD started from 2019. All three approaches were represented from 2013 onwards. In male patients undergoing cystectomy, the prostate and seminal vesicle were removed together via the extended camera port. In female patients undergoing cystectomy, the uterus and anterior vaginal wall were dissected together via the vagina. Lymph node dissection was performed within the internal and external iliac regions.

LRC was performed in the 25-degree Trendelenburg position and using the five-port transperitoneal approach. After total cystectomy, extracorporeal urinary diversion procedures, including ureterocutaneostomy or, creation of an ileal conduit were performed. RARC was performed using the da Vinci system (Si or Xi) in the 25-degree Trendelenburg position, using a six-port transperitoneal approach. Urinary diversion was performed after total cystectomy.

b. Urinary diversion technique

Decisions regarding the type of urinary diversion were based on tumor stage and the patients’ physical condition with the decisions being made after adequate discussions between the doctors and patients.

Extracorporeal urinary diversion

After total cystectomy and lymph node dissection, the robot was rolled out and a midline abdominal incision was made. A 15-cm portion of the ileum 20cm proximal to the ileocecum was used as the ileal conduit, and the intestine was anastomosed using a functional end-to-end anastomosis with an automatic anastomosis machine (Endo GIA; Covidien, USA). The ileum and ureter were anastomosed using the Wallace technique [16]. The ileal conduit anastomosis was reconstructed in the lateral peritoneum using the robot, which was redocked.

Intracorporeal urinary diversion

After total cystectomy and lymph node dissection, patient was returned to the 15-degree Trendelenburg position. The 15-cm portion of the ileum 20cm proximal to the ileocecum was used as the ileal conduit. At this time, the ICG fluorescence imaging method, the ‘firefly system’, was used to confirm the intestinal vessels. Reconstruction of the intestine involved a functional end-to-end anastomosis using a 60-mm SureForm™. The ileum and ureter were anastomosed using the Wallace technique [16]. The ileal conduit anastomosis was reconstructed in the lateral peritoneum. All of these procedures were performed with a transabdominal approach using the robotic technique.

4. Definition of disease recurrence

Disease recurrence was evaluated based on suspected disease progression of radiographic imaging. Local recurrence was defined as the appearance of metastasis to soft tissue or lymph nodes in the pelvis and other distant sites. All sites of recurrence were analyzed to determine oncological outcomes.

5. Statistical analysis

Continuous variables are presented as medians with interquartile range and compared using the Kruskall-Wallis test. Categorical variables were compared using the Chi-squared test. The Kaplan-Meier method and log-rank test were applied to determine RFS and OS estimates. The Cox proportional hazard model was used to identify predictors of oncological outcomes. Statistical significance was set at a two-sided P value of < 0.05. Statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface based on the open-source R statistical software (R Foundation for Statistical Computing, Vienna, Austria).

1. Characteristics of the study patients

A total of 110 patients underwent radical cystectomy at Kochi Medical School between 2013 and 2023. Patients who underwent only urinary diversion (n = 1), ureterocutaneostomy (n = 4), cystectomy with nephroureterectomy (n = 1), or cystectomy indicated for other cancers, such as rectal cancer (n = 3) were excluded in this study. Finally, a total of 101 cases were included in the final analysis.

Among them, 29 participants underwent LRC with ECUD, 40 participants underwent RARC with ECUD, and 32 participants underwent RARC with ICUD. LRC patients were significantly younger than RARC patients.

The median follow-up period in this study was 1485 days for LRC with ECUD, 631 days for RARC with ECUD, and 320 days for RARC with ICUD, respectively. The median follow-up period for LRC was significantly longer compared to that for RARC. There was no difference in gender, smoking history, neoadjuvant chemotherapy, pathological T stage, pathological N stage, positive surgical margin rate, presence of lymphovascular invasion, and adjuvant chemotherapy rate between the three groups.

2. Perioperative outcomes

The total cystectomy time, including lymph node dissection, was 231 minutes for LRC with ECUD, 213 minutes for RARC with ECUD, and 215 minutes for RARC with ICUD, with no statistically significant difference between the three groups (P = 0.05). Two-group comparisons showed no statistically significant differences in total cystectomy time between RARC with ICUD and RARC with ECUD (P = 0.929), RARC with ICUD and LRC with ECUD (P = 0.058), and RARC with ECUD and LRC with ECUD (P = 0.202). The urinary diversion time was 245 minutes for LRC with ECUD, 193 minutes for RARC with ECUD, and 255 minutes for RARC with ICUD, with statistically significant differences between the three groups (P < 0.05). Two-group comparisons showed statistically significant differences in urinary diversion time between RARC with ICUD and RARC with ECUD (P < 0.01) and RARC with ECUD and LRC with ECUD (P < 0.01). There were, however, no significant differences in urinary diversion time between RARC with ICUD and LRC with ECUD (P = 0.559)

Serum WBC count on postoperative days 1, 4, and 7 were not statistically significantly different between the three surgical technique groups (P = 0.21, P = .020, P = 0.32, respectively). There were no statistically significant differences in serum CRP levels between the three surgical procedures on either day (P = 0.15, P = 0.64, P = 0.64, respectively). Comparison of Hb levels on postoperative days 1, 7, and 14 indicated significantly lower levels on postoperative day 1 following LRP among the three groups and the three sampling times (P < 0.05). In particular, Hb levels following LRC were significantly lower when it was performed RALP as compared to LRC with ECUD. No statistically significant differences in Hb levels were observed between the three surgical procedures on postoperative days 7 and 14. The frequency of blood transfusions was also significantly higher in LRC with ECUD than in the other surgical procedures (P < 0.05). The length of hospital stay was significantly shorter with RARC than the other two surgical procedures. In two-group comparisons, RARC with ICUD had the significantly shortest hospital stay compared to RARC with ECUD (P < 0.05) and LRC with ECUD (P < 0.05).

3. Oncological outcomes by surgical approaches and perioperative factors

There were no statistically significant differences in RFS and OS between LRC with ECUD, RARC with ECUD and RARC with ICUD. The estimated RFS at 36 months for RARC with ICUD, RARC with ECUD and LRC with ECUD was 79.9% (95% CI 57.9–91.2), 52.5% (95% CI 31.1–70.1) and 62% (95% CI 40.7–77.5), respectively. The estimated OS at 36 months for RARC with ICUD, RARC with ECUD and LRC with ECUD was 87.1% (95% CI 54.4–96.9), 60.4% (95% CI 33.6–79.3) and 80.7% (95% CI 56.9–91.5), respectively.

Multivariable Cox hazard modeling showed that pathological stage ≥ T3 and pathological N positivity were predictors of poor OS outcomes. Pathological N positivity, pathological stage ≥ T3, positive surgical margin, and positive lymphovascular invasion were factors that predicted disease progression in RFS. Additionally, NAC was associated with improvement in OS (P = 0.08), although adjuvant chemotherapy was not (P = 0.43).

In Japan, surgical treatment for MIBC changed from open radical cystectomy to laparoscopic radical cystectomy, and subsequently, from laparoscopic cystectomy to robot-assisted radical cystectomy. Robotic surgery for MIBC is rapidly becoming commonplace throughout the world and has the shortest history of any surgical procedure [17]. Radical cystectomy with urinary diversion is a highly invasive surgery for MIBC patients due to the prolonged operating time. This might lead to perioperative complications and prolonged hospitalization [9]. Laparoscopy and robotic surgery have made minimally invasive surgery for MIBC possible. Urinary diversion can be performed by either ICUD or ECUD. Although ICUD is a challenging and time-consuming procedure, its performance is gradually enhanced.

In several previous reports, ICUD required greater operative time than ECUD due to the difficulty of the surgical procedure. The longer surgical time for ICUD might increase the length of hospital stay. However, only few reports have focused on oncological outcomes between ICUD and ECUD surgical approaches in Japan. Therefore, we first examined the various effects of ICUD in this study. We secondly focused on oncological outcomes between ICUD and ECUD.

Zang et al. report that open radical cystectomy (ORC) with ECUD had the shortest operative time, and that RARC + ICUD was associated with less blood loss and fewer perioperative complications within 30 days among ORC with ECUD, RCRC with ECUD and RARC with ICUD [18]. Bertolo et al. reported RARC with ECUD showed shorter operative time and the same frequency of perioperative complications between ECUD and ICUD with RARC [19]. Ahmed et al. also reported that RARC with ICUD was associated with a longer operative time, increased frequency of intestinal complications, delayed postoperative recovery, and longer hospital stays compared to RARC with ECUD [17].

The International Robotic Radical Cystectomy Consortium reported long-term oncological outcomes in 743 patients treated by RARC with ECUD or ICUD. In this study, 5-year RFS and OS were 67% and 50%, respectively [9]. More recently, Murthy PB et al. compared oncological outcomes between ORC and RALP in a total of 916 cases [20]. In their study, positive surgical margin rates were higher in ORC compared to RARC. Estimated RFS at 36 months was 71%, 73% and 71% for ORC with ECUD, RARC with ECUD, and RARC with ICUD, respectively, and estimated OS at 36 months was 65%, 70% and 73% for ORC with ECUD, RARC with ECUD, and RARC with ICUD, respectively. They concluded that there were no differences in RFS and OS based on surgical approach. Bertolo et al. also reported no significant differences in oncological outcomes in RARC with ECUD versus ICUD, with comparable recurrence-and metastasis-free survivals at a mean follow-up of 18 months [19]. Nguyen et al. reported that recurrence was associated with adverse pathologic features, but not with surgical approach [21].

In this study, there were no differences in operative time for total cystectomy in terms of the surgical approach, whether LRC or RARC. However, ICUD was associated with significantly longer operative times than ECUD. Hemoglobin levels were significantly lower on postoperative day 1 following LRC compared to RARC, and the frequency of blood transfusions was significantly higher with LRC as compared to RARC. The length of hospital stay was also significantly shorter for RARC with ICUD compared to other surgical approaches. There were no significant differences in RFS and OS between ECUD and ICUD. Multivariable Cox hazard modeling showed that pathological stage ≥ T3 and pathological N positivity were predictors of poor OS outcome. Additionally, pathological stage ≥ T3, pathological N positivity, positive surgical margins, and positive lymphovascular invasion were predictive factors of disease progression in terms of RFS. Thus, our single institutional study, results were not significantly different from those of previously reported studies. There are some limitations to the present study, such as that it was a single institutional comparison of three surgical approaches. Additionally, the study was retrospective and the cohort size was small. Hence, further large size randomized studies are needed to validate our results.

Author contribution

Concepualization and Methodology; Hideo Fukuhara

Data curation, formal analysis and investigation, draft preparation; Hiroto Osakabe, Tomoya Nao, Tsutomu Shimamoto

Writing original draft; Hideo Fukuhara

Review and editing; Satoshi Fukada, Kenji Tamura, Shingo Ashida

Supervision; Takashi Karashima, Keiji Inoue

Acknowledgements

We are grateful Forte Science Communications for the English language editing.

Conflict of Interest The authors declare that they have no conflict of interest.

Ethics statement

All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and in later amendments or comparable ethical standards. The institutional review board in Kochi Medical School has approved this study.

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Tables 1 to 4 are available in the Supplementary Files section.

Table.pptx
Table 1 Patients’ characteristics RARC: robot-assisted radical cystectomy; ECUD: extracorporeal urinary diversion; ICUD: intracorporeal urinary diversion; LRC: laparoscopic radical cystectomy. Table 2 Perioperative outcomes WBC: white blood cell count; Hb: hemoglobin; CRP: C-reactive protein; POD: postoperative day. Table 3 Cox proportional hazards model of patients’ characteristics RARC: robot-assisted radical cystectomy; ECUD: extracorporeal urinary diversion; ICUD: intracorporeal urinary diversion; LRC: laparoscopic radical cystectomy; HR: hazard ratio; CI: confidence interval. Table 4 Cox proportional hazards model of perioperative outcomes WBC: white blood cell count; Hb: hemoglobin; CRP: C-reactive protein; POD: postoperative day; HR: hazard ratio; CI: confidence interval.

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Version 1

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You are reading this latest preprint version

Comparison of perioperative and oncological outcomes between extracorporeal and intracorporeal urinary diversion following laparoscopic radical cystectomy and robot-assisted radical cystectomy

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Materials and methods

1. Patients’ characteristics

2. Perioperative management protocol

a. Radical cystectomy technique

b. Urinary diversion technique

Extracorporeal urinary diversion

Intracorporeal urinary diversion

4. Definition of disease recurrence

5. Statistical analysis

Results

1. Characteristics of the study patients

2. Perioperative outcomes

3. Oncological outcomes by surgical approaches and perioperative factors

Discussion

Declarations

References

Tables

Supplementary Files

Status:

Version 1