ROBOTIC VS OPEN RADICAL CYSTECTOMY A REVIEW Colin Lundeen December 14, 2016 Objectives Review the history of radical cystectomy Critically analyze recent RCTs comparing open radical cystectomy (ORC) to robot assisted radical cystectomy (RARC) Summarize and evaluate available data on ORC vs RARC Discuss future directions for RARC 1
BACKGROUND Bladder Cancer 4 th and 12 th most common non-cutaneous solid malignancy in men, women respectively 2/3 present with non muscle invasive disease 2/3 will recur 20-30% will progress to muscle invasive disease 1/3 present with muscle invasive disease 85% 2 year disease specific mortality if left untreated 1 Gold standard treatment is neoadjuvant chemotherapy with radical cystectomy Nearly 50% of MIBC do not undergo curative therapy 2 Of those who did choose curative therapy Cystectomy 45% Curative radiation therapy 7.6% 1. Prout et al Cancer 1956 2. Gray et al EurUrol 2013 2
Who should be offered cystectomy? Muscle invasive - T2-T4a; N0-Nx; M0 All patients who are deemed surgical candidates gold standard Non muscle invasive 1 T1HG with variant features, LVI, concomitant CIS, large size (>3cm) early high-grade recurrence at 3 months persistent T1HG on restaging TUR invasive tumours involving bladder diverticula High risk disease unresponsive to BCG 1. Kassouf et al CUAJ 2015 HISTORY OF CYSTECTOMY 3
Surgical Management of Bladder Cancer Bardenheuer 1888 first reported cystectomy for bladder cancer 1939 peri-op mortality 35% 1 By 1956 peri-op mortality only 17% 2 4 year survival 18% over ½ received pelvic exenteration Contemporary ORC 3 30 day mortality 1.5% Overall complications 64% GI, infectious, wound related Clavien 3-5: 13% 1. HinmanInt SocUrol Rep 1939 2. Whitmore and Marshall Cancer 1956 3. Shabsigh et al Eur Urol 2009 Surgical Management of Bladder Cancer First Laparoscopic radical cystectomy reported in 1995 by Sanchez de Badajos et al 1 First Robot assisted radical cystectomy reported in 2003 by Menon et al 2 In the US from 2005 2010 use of minimally invasive techniques for RC increased from 0.8% - 10.3% 3 1. Sanchez de Badajoset al J Endourol 1995 2. Menon et al BJUI 2003 3. Cohen et al. Urology 2014 4
Early reports of RARC Wang et al BJUI 2008 Decreased blood loss, transfusions, time to diet, length of stay (5 vs 8 days) Increased OR time No difference in lymph nodes, complications ORC had much higher rate of extravesical disease (57 vs 28%) Ng et al Eur Urol 2010 Decreased 30 day overall (41% vs 59%) and major complications (8% vs 31%) Lower blood loss (460ml vs 1172ml) Shorter hospital stay (5.5 vs 8 days) No difference in lymph node yield or positive surgical margins RANDOMIZED CONTROLLED TRIALS 5
Prospective Randomized Controlled Trial of Robotic vs Open Radical Cystectomy for Bladder Cancer: Perioperative and Pathologic Results Nix et al. Eur Urol 2010 Number of patients 41 à RARC 21 ORC 20 Design Centers 1 Inclusion criteria Exclusion criteria Primary outcome Secondary outcomes Non-inferiority Patients with clinically localized urothelial carcinoma of the bladder 1. Not considered surgical candidates for either approach 2. Not allowing randomization 3. Preconceived preference for a specific surgical modality Lymph node yield (4 node difference) Operative time, EBL, return of bowel function, time to discharge, in-house analgesia, Positive margin status Results Pathology Nix et al. Eur Urol 2010 6
Results Perioperative Nix et al. Eur Urol 2010 Perioperative Outcome and Oncologic Efficacy from a Pilot Prospective Randomized Clinical Trial of Open vs Robotic Assisted Radical Cystectomy Parekh et al. J Urol 2013 Number of patients 39 à RARC 20 ORC 19 Design Centers 1 Inclusion criteria Exclusion criteria Primary outcome Secondary outcomes Pilot study Biopsy proven bladder cancer T1-T3, N0, M0 Candidates for open or robotic approach Inability to give informed consent Multiple prior abdominal/pelvic surgeries, morbid obesity, clinical stage t4, bulky nodes Establish feasibility of randomizing patients Obtain preliminary data on oncologic efficacy (surgical margin status, total lymph node count) Measure perioperative outcomes (EBL, operative time, transfusion requirement, time to return of bowel function, length of stay) complications 7
Results Outcomes Parekh et al. J Urol 2013 Results Pathology Parekh et al. J Urol 2013 No Difference 8
Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial Bochner et al. Eur Urol 2015 Number of patients 118 à RARC 60 ORC 58 Design Centers 1 Inclusion criteria superiority Bladder cancer: clinical stage Ta-T3, N0-3, M0 Medically cleared for surgery Age > 18 years Exclusion criteria Prior pelvic radiation, clinical stage T4 or M1, contraindication for Trendelenberg position, extensive prior abdominal surgery Primary outcome Secondary outcomes Overall 90 day grade 2-5 complications High grade complications, EBL, operative time, pathologic outcomes, 3 and 6 month QOL, total operative room and inpatient costs Results Outcomes Bochner et al. Eur Urol 2015 9
Results Costs Bochner et al. Eur Urol 2015 A Single-centre Early Phase Randomised Controlled Three-arm Trial of Open, Robotic and Laparoscopic Radical Cystectomy (CORAL) Khan et al. Eur Urol 2016 Number of patients 59 à RARC 20 ORC 20 LRC 19 Design Centers 1 Inclusion criteria Exclusion criteria Primary outcome Secondary outcomes superiority 18-80 years old requiring radical cystectomy for MIBC or high-risk NMIBC Severe cardiorespiratory comorbidities, extensive abdominopelvic surgery or radiation 30 and 90 day complication rates Perioperative measures (operative time, EBL, delay in bowel function, length of hospital stay) Pathologic outcomes (margin status, # of lymph nodes retrieved) 12 month oncologic outcomes Quality of Life 10
Results Khan et al. Eur Urol 2016 Results Khan et al. Eur Urol 2016 11
SUMMARY OF DATA Early meta-analysis including retrospective data Tang et al EJSO 2014 12
Early meta-analysis including retrospective data Tang et al EJSO 2014 OR time: 70 minutes longer EBL: 600 cc less LOS: 4.5 days shorter Lymph node yield: 2 more Time to diet: 1.5 days less Complications: odds ratio 0.50 (95% CI 0.34-0.72, p=0.02) Pathologic stage: odds ratio 1.93 for pt2 or lower (95% CI 1.29-2.88, p=0.001) Systematic review and meta-analysis of RCTs Tan et al PLOS One 2016 13
Systematic review and meta-analysis of RCTs Blood loss Tan et al PLOS One 2016 Systematic review and meta-analysis of RCTs OR time Tan et al PLOS One 2016 14
Systematic review and meta-analysis of RCTs Length of stay Tan et al PLOS One 2016 Systematic review and meta-analysis of RCTs All complications Tan et al PLOS One 2016 15
Systematic review and meta-analysis of RCTs Major complications Tan et al PLOS One 2016 Systematic review and meta-analysis of RCTs Positive surgical margin Tan et al PLOS One 2016 16
Systematic review and meta-analysis of RCTs Lymph node yield Tan et al PLOS One 2016 Systematic review and meta-analysis of RCTs Conclusions Favors RARC No Difference Favors ORC Estimated blood loss Overall complications OR time Major complications Lymph node yield Positive surgical margin Length of stay Tan et al PLOS One 2016 17
Recommendations - CUA Laparoscopic and robot-assisted radical cystectomy are alternative surgical options to open radical cystectomy. Current data have not demonstrated clear advantages or disadvantages in terms of cancer control and functional outcomes of these minimally invasive surgical approaches. (Level III Grade C) 1. Kassouf et al CUAJ 2016 Recommendations EUA 1 1. Witjeset al EurUrol 2014 18
FUTURE DIRECTIONS Number of Patients 320 à 160/160 Design Randomized, non-inferiority (15%) Centers 15 Inclusion criteria Exclusion criteria Primary outcome Secondary outcomes T1-T4, N0-N1, M0 bladder Ca or refractory CIS Absolute: Inability to give consent, age <18 or >99, pregnancy Relative: prior major abdo/pelvic surgery, any condition that would preclude use of pneumoperitoneum 2 year progression free survival Pathologic (lymph nodes, surgical margins), perioperative (EBL, transfusion, OR time, length of stay, analgesic requirement), Morbidity (perioperative and up to 90 days), cost quality of life, 19
Long term survival Raza et al Eur Urol 2015 702 patients - 11 centers, 6 countries Pathology Organ confined disease 62% Positive surgical margins -8% Positive lymph nodes 21% (median lymph node yield 16) Non organ confined disease and positive surgical margins associated with poor outcomes Five year survival Recurrence free 67% Cancer specific 75% Overall 50% IntracorporealUrinary Diversion (ICUD) International Robotic Cystectomy Consortium 935 cystectomies (2002-2011) 167 ICUD vs 768 Extracorporeal urinary diversion (ECUD) No difference in operative time (414 min) or LOS (9 vs 8 days) Post op complication lower in ICUD (32% reduction) 90 day readmission rate lower (12 vs 19%) Significantly lower GI complication rates (10 vs 23%) Ahmed et al EurUrol 2014 20
Intracorporeal RARC vs ORC Tan et al Uro Onc 2016 184 patients 94 ORC, 90 RARC Bias: 65 vs 39 % pt2 or greater in ORC (lower neoadjuvant chemo 22 vs 34%) No difference in: Recurrence free survival Cancer specific survival Overall survival Retrospective review of 383 consecutive patients (120 ORC, 263 RARC) 2001-2014 Similar number of recurrences between the groups RARC was not an independent predictor of recurrence *Distinct patterns of distant recurrence Peritoneal carcinomatosis and extrapelvic lymph nodes were increased in RARC 21
Objective: to assess for predictors of atypical recurrence Predictors of recurrence (any location): Tumor stage Lymphovascular invasion Positive surgical margins Conclusion: Atypical recurrence (peritoneal carcinomatosis and extrapelvic lymph nodes) is chiefly influenced by tumor biology, not surgical approach Conclusions RARC is associated with a longer OR time but decreased blood loss compared to ORC There is no difference between RARC and ORC with respect to: Overall or major complications Lymph node yield Length of stay Positive surgical margins Utilization of RARC has increased despite lack of level 1 evidence Results from the RAZOR trial will provide the first level 1 evidence comparing RARC with ORC A prospective, randomized trial looking at ICUD is required to further assess any benefit to this technique 22