Randomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes

doi:10.1016/j.eururo.2018.04.030

European Urology

Volume 74, Issue 4, October 2018, Pages 465-471

https://doi.org/10.1016/j.eururo.2018.04.030 Get rights and content

Abstract

Background

Open radical cystectomy (ORC) has proven to be an important component in the treatment of high-risk bladder cancer (BCa). ORC surgical morbidity remains high; therefore, minimally invasive surgical techniques have been introduced in an attempt to improve patient outcomes.

Objective

To compare cancer outcomes in BCa patients managed with ORC or robotic-assisted radical cystectomy (RARC).

Design, setting, and participants

A prospective, randomized trial was completed between 2010 and 2013. Patients were randomized to ORC/pelvic lymphadenectomy (PLND) or RARC/PLND, with all undergoing open/extracorporeal urinary diversion. Median follow-up was 4.9 (IQR: 3.9–5.9) yr after surgery among surviving patients.

Outcome measurements and statistical analysis

Secondary outcomes to the trial included recurrence-free, cancer-specific, and overall survival.

Results and limitations

The trial randomized 118 patients who underwent RC/PLND and urinary diversion. Sixty were randomized to RARC and 58 to ORC. Four RARC-assigned patients refused randomization and received ORC; however, an intention to treat analysis was performed. No differences were observed in recurrence (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.69–2.36; p = 0.4) or cancer-specific survival (p = 0.4). No difference in overall survival was observed (p = 0.8). However, the pattern of first recurrence demonstrated a nonstatistically significant increase in metastatic sites for those undergoing ORC (sub-HR [sHR]: 2.21; 95% CI: 0.96–5.12; p = 0.064) and a greater number of local/abdominal sites in the RARC-treated patients (sHR: 0.34; 95% CI: 0.12–0.93; p = 0.035). The major limitation to this study is that the trial was not powered to determine differences in cancer recurrences, survival outcomes, or patterns of recurrence.

Conclusions

The secondary outcomes from our randomized trial did not definitively demonstrate differences in cancer outcomes in patients treated with ORC or RARC. However, differences in observed patterns of first recurrence highlight the need for future studies.

Patient summary

Of 118 patients randomly assigned to undergo radical cystectomy/pelvic lymphadenectomy and urinary diversion, half were assigned to open surgery and half to robot-assisted techniques. We found no difference in risk of recurring or dying of bladder cancer between the two groups.

Introduction

Radical cystectomy (RC) with regional pelvic lymphadenectomy (PLND) is the established standard of care for treating high-risk bladder cancer (BCa) [1], [2]. BCa is common in older individuals and strongly linked to smoking exposure. Performing extensive pelvic surgery and reconstruction of the urinary system in an elderly, comorbid population carries significant surgical risks. The development of minimally invasive surgical techniques has been widely used in a variety of surgical procedures. One major goal associated with the adaptation of minimally invasive techniques is to minimize surgical morbidity and improve recovery.

Robot-assisted RC (RARC) was introduced in hopes of decreasing the substantial morbidity following standard of RC and urinary diversion. Several retrospective series had reported perioperative outcomes including complications following RARC with either open or intracorporeal techniques [3], [4], [5], [6]. We reported our results of a randomized controlled study designed to compare complications between open RC (ORC) and RARC [7], [8]. In that trial, we reported no large differences in 90-d overall complications, high-grade complications, or hospital length of stay. Pathologic outcomes including positive soft tissue margin (PSTM) rates and lymph node yield were similar between open and robotic techniques. Margin rates and lymph node yields were similar to previously reported benchmarks.

Long-term oncologic outcomes following RARC have not been well documented in the reported literature. Here, we describe the oncologic outcomes from our ORC versus RARC randomized controlled trial, including the secondary endpoints of recurrence-free survival, overall survival, and patterns of first recurrence.

Section snippets

Patients

Patients with BCa scheduled to undergo RC and PLND were recruited from the urology clinics at Memorial Sloan Kettering Cancer Center (MSKCC) between March 2010 and March 2013. The study protocol was approved by the Institutional Review Board, and all patients were required to provide written consent prior to enrollment and surgery. Patients were randomized 1:1 to undergo RARC or ORC using MSKCC's Clinical Research Database, a secure system that ensures allocation concealment.

Eligible patients

Patient population

Patient demographics and disease characteristics of the two groups were similar (Table 1). Pathologic staging of the two groups was not significantly different (Table 1). Pathologic stage T4 was found in five patients (8.3%) undergoing RARC and four (6.9%) undergoing ORC. There was no difference in the lymph node yield based on the extent of dissection and PSTM rate between RARC (3.6%) and ORC (4.8%).

Among the 118 enrolled patients, the median follow-up was 4.9 (IQR: 3.9–5.9) yr after surgery

Discussion

RC and PLND have become the established gold standard for managing nonmetastatic high-risk BCa. The critical surgical tenets of this procedure have been developed over decades and focus on wide resection of the bladder, surrounding tissues, and adjacent organs as well as avoidance of entry into the bladder and thoroughness of PLND to optimize local and regional disease control. Benchmarks for recurrence-free survival following RC using standard open surgical techniques are strongly affected by

Conclusions

In this secondary analysis of cancer outcomes from our randomized controlled trial, we did not find a difference in overall recurrence rates and cancer-specific survival between ORC and RARC for BCa. The observed pattern of first recurrence after ORC and RARC in this study suggests an increased risk for local/abdominal recurrences following RARC. Future studies should be designed to definitively assess if alterations in the patterns of recurrence truly exist. Although both groups demonstrated

References (31)

R.S. Johar et al.
Complications after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium
Eur Urol
(2013)
M. Nazmy et al.
Early and late complications of robot-assisted radical cystectomy: a standardized analysis by urinary diversion type
J Urol
(2014)
M.E. Wechter et al.
Complications in robotic-assisted gynecologic surgery according to case type: a 6-year retrospective cohort study using Clavien-Dindo classification
J Minim Invasive Gynecol
(2014)
W.S. Tan et al.
In-depth critical analysis of complications following robot-assisted radical cystectomy with intracorporeal urinary diversion
Eur Urol Focus
(2017)
B.H. Bochner et al.
Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: a randomized clinical trial
Eur Urol
(2015)
S.J. Raza et al.
Oncologic outcomes following robot-assisted radical cystectomy with minimum 5-year follow-up: the Roswell Park cancer institute experience
Eur Urol
(2014)
E. Xylinas et al.
Robotic-assisted radical cystectomy with extracorporeal urinary diversion for urothelial carcinoma of the bladder: analysis of complications and oncologic outcomes in 175 patients with a median follow-up of 3 years
Urology
(2013)
B. Yuh et al.
Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy
Eur Urol
(2015)
S.J. Raza et al.
Long-term oncologic outcomes following robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium
Eur Urol
(2015)
K.A. Guru et al.
Robot-assisted radical cystectomy and pelvic lymph node dissection: initial experience at Roswell Park Cancer Institute
Urology
(2007)

J. Nix et al.

Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results

Eur Urol

(2010)

A.A. Hussein et al.

Early oncologic failure after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium

J Urol

(2017)

R.S. Pruthi et al.

Robotic assisted laparoscopic radical cystoprostatectomy: operative and pathological outcomes

J Urol

(2007)

B.E. Yuh et al.

Standardized analysis of frequency and severity of complications after robot-assisted radical cystectomy

Eur Urol

(2012)

N.J. Hellenthal et al.

Surgical margin status after robot assisted radical cystectomy: results from the International Robotic Cystectomy Consortium

J Urol

(2010)

Cited by (206)

Atlas of Intracorporeal Orthotopic Neobladder Techniques After Robot-assisted Radical Cystectomy and Systematic Review of Clinical Outcomes
2024, European Urology
Multiple and heterogeneous techniques have been described for orthotopic neobladder (ONB) reconstruction after robot-assisted radical cystectomy. Nonetheless, a systematic assessment of all the available options is lacking.
To provide the first comprehensive step-by-step description of all the available techniques for robotic intracorporeal ONB together with individual intraoperative, perioperative and functional outcomes based on a systematic review of the literature.
We performed a systematic review of the literature, and MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched to identify original articles describing different robotic intracorporeal ONB techniques and reporting intra- and perioperative outcomes. Studies were categorized according to ONB type, providing a synthesis of the current evidence. Video material was provided by experts in the field to illustrate the surgical technique of each intracorporeal ONB.
Nine different ONB types were identified: Studer, Hautmann, Y shape, U shape, Bordeaux, Pyramid, Shell, Florence Robotic Intracorporeal Neobladder, and Padua Ileal Neobladder.
Continuous and categorical variables are presented as mean ± standard deviation and as frequencies and proportions, respectively.
Of 2587 studies identified, 19 met our inclusion criteria. No cohort studies or randomized control trials comparing different neobladder types are available. Available techniques for intracorporeal robotic ONB reconstruction have similar operative time, estimated blood loss, intraoperative complications, and length of stay. Major variability exists concerning postoperative complications and functional outcomes, likely related to reporting bias.
Several techniques are described for intracorporeal ONB during robot-assisted radical cystectomy with comparable perioperative outcomes. We provide the first step-by-step surgical atlas for robot-assisted ONB reconstruction. Further comparative studies are needed to assess any advantage of one technique over others.
Patients elected for radical cystectomy should be aware that multiple techniques for robotic orthotopic neobladder are available, but that current evidence does not favor one type over the others.
Oncologic outcomes of intravesical therapy in the management of nonmuscle invasive bladder cancer with variant histology
2024, Urologic Oncology: Seminars and Original Investigations
There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center.
A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific, and overall survival. Survival time was computed from the date of initiation of intravesical therapy to the date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan-Meier method with log rank was utilized to compare survival time between VH sub-groups.
Ninety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval [CI]: 2–46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes.
In this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment.
Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy
2024, Urology
To compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG vs immediate radical cystectomy. High-risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life.
Cost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression.
Mean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 quality-adjusted life years (QALYs) compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an incremental CE ratios (ICER) of $7120/QALY.
The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the 5-year recurrence rate of HG T1 was less than 56% or the 5-year progression rate to MIBC was less than 4%.
At current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.
Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials
2023, European Urology
Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear.
This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures.
Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022.
Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03–0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02–3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193–450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65–3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39–112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI –1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54–1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29–0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4–15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients.
RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events.
This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen.
Cost-analysis of robot-assisted radical cystectomy in Europe: A cross-country comparison
2023, European Journal of Surgical Oncology
Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries.
Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient.
A total of 490 patients were included. Median operative time was 300(270–360) minutes and median hospital length-of-stay was 11(8–15) days. The average total cost of RARC was 14.794€ (95%CI 14.300–15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments.
Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.
Robot-assisted vs. open radical cystectomy: Systematic review and meta-analysis of randomized controlled trials
2023, Actas Urologicas Espanolas
En la última década se han puesto en marcha varios ensayos controlados aleatorizados (ECA) con el objetivo de evaluar la seguridad quirúrgica y la eficacia oncológica de la cistectomía radical asistida por robot (CRAR) frente a la cistectomía radical abierta (CRA) en pacientes con cáncer de vejiga. El objetivo del estudio fue realizar una revisión sistemática y un metaanálisis de ECA para comparar los resultados perioperatorios y oncológicos de ambas.
Se realizó una búsqueda bibliográfica hasta julio de 2022 en las bases de datos PubMed/Medline, Embase y Web of Science. Se siguieron las directrices de la declaración PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) para identificar los estudios elegibles. Los criterios de evaluación fueron los resultados intraoperatorios, postoperatorios y oncológicos de la CRAR frente a la CRA.
Un total de 8 ECA con 1.024 pacientes cumplieron los criterios de inclusión. La CRAR se asoció con un tiempo quirúrgico mayor (media de 92,34 min, IC 95%: 83,83-100,84; p < 0,001) y una tasa de transfusión de sangre menor (odds ratio [OR] 0,43; IC 95%: 0,30-0,61; p < 0,001). No se observaron diferencias en cuanto a las complicaciones globales (p = 0,28) ni graves (p = 0,57) a los 90 días, la duración de la estancia hospitalaria (p = 0,18), la recuperación de la función intestinal (p = 0,67), la calidad de vida relacionada con la salud (p = 0,86), la recurrencia (p = 0,77) ni la progresión (p = 0,49) de la enfermedad entre los 2 abordajes. La principal limitación reside en el bajo número de pacientes incluidos en el 50% de los ECA revisados.
Este estudio respalda la no inferioridad de la CRAR respecto a la CRA en términos de seguridad quirúrgica y resultados oncológicos. El beneficio de tasas reducidas de transfusión sanguínea obtenido con la CRAR debe sopesarse con relación a los costes derivados del procedimiento.
Several randomized controlled trials (RCTs) have been launched in the last decade to examine the surgical safety and oncological efficacy of robot-assisted (RARC) vs. open radical cystectomy (ORC) for patients with bladder cancer. The aim of the study was to perform a systematic review and meta-analysis of RCTs to compare the perioperative and oncological outcomes of RARC vs. ORC.
A literature search was conducted through July 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The outcomes were intraoperative, postoperative, and oncological outcomes of RARC vs. ORC.
A total of 8 RCTs comprising 1,024 patients met our inclusion criteria. RARC was associated with longer operative time (mean 92.34 min, 95% CI: 83.83-100.84, P < 0.001) and lower blood transfusion rate (Odds ratio [OR] 0.43, 95% CI: 0.30-0.61, P < 0.001). No differences emerged in terms of 90-day overall (P = 0.28) and major (P = 0.57) complications, length of stay (P = 0.18), bowel recovery (P = 0.67), health-related quality of life (P = 0.86), disease recurrence (P = 0.77) and progression (P = 0.49) between the 2 approaches. The main limitation is represented by the low number of patients included in half of RCTs included.
This study supports that RARC is not inferior to ORC in terms of surgical safety and oncological outcomes. The benefit of RARC in terms of lower blood transfusion rate need to be balanced with the cost related to the procedure.

View all citing articles on Scopus

¹: Current affiliation: Division of Urology, Department of Surgery, Lions Gate Hospital, North Vancouver, BC, Canada.

View full text

Platinum Priority – Bladder Cancer – Editor's ChoiceEditorial by Bertram Yuh, Kevin Chan and Timothy Wilson on pp. 472–473 of this issueRandomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes

Abstract

Background

Objective

Design, setting, and participants

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Introduction

Section snippets

Patients

Patient population

Discussion

Conclusions

Eur Urol

J Urol

J Minim Invasive Gynecol

Eur Urol Focus

Eur Urol

Eur Urol

Urology

Eur Urol

Eur Urol

Urology

Eur Urol

J Urol

J Urol

Eur Urol

J Urol

Platinum Priority – Bladder Cancer – Editor's Choice
Editorial by Bertram Yuh, Kevin Chan and Timothy Wilson on pp. 472–473 of this issue
Randomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes