Robotic Cystectomy – Role in 2017

Dipen J. Parekh

Professor and Chairman, Department of Urology,

Victor A Politano Endowed Chair in Urology, University of Miami Miller School of

Medicine

Take Home Message

Most Important

• Patient outcome

• Surgeon Skill

Least Important

• Surgeon Ego/Bias

• Marketing /Hype

How do we evaluate surgical quality for bladder cancer ?

• Perioperative morbidity

• Pathologic outcomes

• Quality of Life

• Oncologic efficacy

ROBOTIC CYSTECTOMY

• Cost

• Utilization trends

• Type of Diversion – Extra /Intra Corporeal

• Future

Perioperative Outcomes

Variable Comparison between robotic and open cystectomy

Overall complications

Significantly lower at both 30days and 90days in RARC

Minor complications

Significantly less Clavien II complications in some meta-analyses, no difference in others

Major complications

Significantly less Clavien III-IV complications in some meta-analyses, no difference in others

References: Novara et al. Eur Urol, 2015. Xia et al. Plos One, 2015. Luchey et al. Cancer Control, 2015 Tang et al. EJSO, 2014. Ishii et al. J Endourol, 2014.

Perioperative Outcomes Variable Comparison between robotic and open cystectomy

EBL (ml) Significantly reduced in RARC across multiple studies

Transfusion requirement

Open cystectomy average requirement greater than RARC

OR time

RARC OR time longer but varies with type of diversion and surgical experience

Narcotic use Significantly reduced in RARC in certain studies

Time to oral diet Significantly faster in RARC in certain studies

Length of stay Shorter LOS with RARC across multiple studies

References: Novara et al. Eur Urol, 2015. Xia et al. Plos One, 2015. Luchey et al. Cancer Control, 2015 Tang et al. EJSO, 2014

• Randomized, controlled trial with a primary outcome of perioperative complication rate

• All patients had pTa-3 N0 M0 disease • 58 patients randomized to ORC 60 patients randomized to RARC • Enrollment closed early at interim analysis

due to futility Bochner BH et al. A Randomized Trial of Robot-Assisted Laparoscopic Radical Cystectomy. N Engl J Med 2014;371(4):389-390.

Results

Bochner BH et al. A Randomized Trial of Robot-Assisted Laparoscopic Radical Cystectomy. N Engl J Med 2014;371(4):389-390.

J Urol, Feb 2013

Patients with Invasive Bladder cancer eligible for RARC

Open Radical Cystectomy (ORC)

Robotic Assisted Radical Cystectomy (RARC)

END POINTS Oncologic Efficacy Soft Tissue Margins Lymph Node counts Pathologic Stage Perioperative Outcomes Quality of Life Outcomes - VCI at 3,6,9 and 12 months Functional Recovery - ADL, IADL, TUG at 3,6 months

Pathological Outcomes

Variable Comparison between robotic and open cystectomy

Positive surgical margins

No significant difference in positive margin rates in meta-analyses RARC rates ranged from 0-26% (mean 5.6%) • pT2: 1-1.5% • pT3 and above: 0-25% (IRCC 16.6%, 39% for pT4)

Lymph node yield

RARC has shown increased LN yield versus open cystectomy in some meta-analyses

References: Yuh et al. Eur Urol, 2015. Xia et al. Plos One, 2015. Luchey et al. Cancer Control, 2015. Tang et al. EJSO, 2014. Ishii et al. J Endourol, 2014.

• Demonstrated non-inferiority of LN yield – 19 vs 18 LN

• Improvement in other parameters

Nix et al, Eur Urol (2009)

• FACT – Vanderbilt Cystectomy Index • Preoperative and 3,6,9 and 12 months

post op • Total of 40 patients , 2009-11 • 20 patients in ORC and RARC arm

Messer J et al, BJUI Aug 2014

• Return to baseline QOL at 3 months in both groups

• No significant difference between ORC and RARC in HRQOL

• Perceived benefits of Robotic approach does not translate into HRQOL benefits

Messer J et al, BJUI Aug 2014

Oncologic Outcomes for RARC Recurrence free survival IRCC: 67% at 5-yr

Cleveland Clinic: 54% at 10-yr

Cancer-specific survival IRCC: 75% at 5-yr Cleveland Clinic: 63% at 10-yr (100%, 91%, 74%, 77%, 56%, 0% for pT0, pTis/Ta, pT1, pT2, pT3, pT4)

Overall survival IRCC: 50% at 5-yr Cleveland Clinic: 35% at 10-yr (67%, 73%, 53%, 50%, 16%, 0% for pT0, pTis/Ta, pT1, pT2, pT3, pT4)

References: 1. Raza et al. Eur Urol, 2015. Snow-Lisy et al. Eur Urol, 2014.

• Single institution comparison of perioperative costs between ORC/RARC

• Greatest impact on perioperative costs : OR time LOS When comparing direct OR costs, RARC 16%

more expensive However, for actual total patient costs, RARC

38% less expensive due to reduced LOS Martin A et al Urology 2011

• From 2009-2011: 3,733 RARC/29,719 total RC (12.6%), Unchanged trend of around 12% over 3 years

• RARC patients more likely to be men, higher median

income, and managed at academic centers (p < 0.05) • Cost: Higher median hospital costs with robotic surgery

Monn MF et al. Urol Oncol 2014;32:785-790.

Outcomes of Interest • 90 day mortality

• 90 day complication rate

• Length of stay

• Readmission rates

• Direct Costs

Methods • Population based

Administrative database • Propensity matching • 2004-2010 • 279 US Hospitals • 34,672 ORC versus • 2101 RARC

LEOW et al, Eur Urol Jan 2014

LEOW et al, Eur Urol Jan 2014

• No difference in major complications/readmissions

• RARC - decreased

minor complication

• RARC - decreased LOS (10.2 vs 11.8)

• RARC – Increased OR time

• No difference in mortality, morbidity and costs for high volume surgeons and hospitals

LEOW et al, Eur Urol Jan 2014

LEOW et al, Eur Urol Jan 2014

For RARC to be cost effective, on threshold analysis, LOS 7 days OR time <380 mins

Urinary Diversion

Extracorporeal versus

Intracorporeal ?

RARC: Standard Treatment Yet ?

• Multi-institutional, prospective, non-inferiority trial • Evaluating oncological outcomes, surgical

complications and HRQL measures of ORC vs RARC in patients with bladder cancer.

Extracorporeal Urinary diversion

• At present, approximately 95% of diversions are

performed by the extracorporeal approach • Benefits - No additional learning curve needed - Shorter operative time - Long-term data - Reproducible

Extracorporeal Urinary diversion

Three RCT showed that ECUD in the setting of RARC is comparable to open approach

RARC: Steep Learning Curve!

• RARC –challenging but reproducible throughout multiple centers.

• Acceptable level of proficiency achieved by the 30th case.

Steep learning curve and low surgical volume

10 years to overcome the learning curve!

ICUD

Intracorporeal urinary diversion Presumed Advantages • Minimize tissue handling • Minimize fluid imbalance • Limit ureteral mobilization • Cosmesis • Reduce Incision related

morbidity • Earlier return of bowel

function • Overall improved

perioperative morbidity

Challenges • OR times • Multiple teams/surgeons • Surgeon fatigue • Steep Learning curve • Increased Costs • Increased complications

during learning curve • Short follow up

Azzouni et al, Eur Urol Dec 2012

Azzouni et al, Eur Urol Dec 2012

Intracorporeal Neobladder

• Combined USC/Karolinska epereince • 132 patients • Mean OR time 7.6 hours • Mean LOS 11 days

Desai M et al J Urol Epub Aug 2014

Desai M et al J Urol Epub Aug 2014

Desai M et al J Urol Epub Aug 2014

Analysis of Intracorporeal Compared with Extracorporeal Urinary Diversions After Robotic

Cystectomy: IRCC

• 935 patients at 18 institutions • 167 intracorporeal urinary diversions

– 106 ileal conduit, 61 neobladder • Retrospective analysis comparing IC vs. EC

– Perioperative outcomes – Postoperative complications

Ahmed, K. et. al., European Urology (2014) 65: 340-47

• Operative time, EBL, and LOS were similar in both groups (all p values

>0.05) • ICUD: 32 % less likelihood of complications on multivariate analysis (OR:

0.68; p=0.02)

ECUD ICUD p-value

Complication rates 43% 35% 0.07

GI complications 20% 10% <0.001

Infections 17% 12% 0.035

High Grade Complications (Clavien 3-5) 18% 18% not significant

Readmission 30d 15% 5% <0.0001

Readmission 90d 19% 12% .016

Mortality 90d 4.9% 1.6% .043

Several Limitations need to be addressed: ✖Retrospective, non-randomized ✖Selection bias (easy cases selected for ICUD) ✖Variability in surgical expertise (ICUD most likely to

be performed by surgeons with the highest level of robotic skills)

✖Data on complications were lacking in 117 patients ✖Description of complications are vague (urine leak?

stricture?)

IRCC Conclusions

• Safe and feasible

• LOS, complication rates, EBL similar • Difficult to reach meaningful conclusion

due to huge selection bias

Conclusions

• Intracorporeal diversion feasible and safe

• Intracorporeal diversion - lengthy with steep learning curve

• Advantages of ICUD over ECUD remain

hypothetical at present

• Only RCT of ICUD versus ECUD will answer the question

Future Direction

Prospective Multiinstitutional RCT -RAZOR comparing RARC to ORC for Bladder Cancer

Principal Investigator Dipen Parekh Participating Institutions • University of Miami • UTSan Antonio • Vanderbilt • Stanford • University of Chicago • Ohio State University • UC Irvine • Mayo Clinic

• University of North Carolina

• Loyola • University of Minnesota • Washington University • UVA – Charlottesville • University of Michigan • Cancer Research and

Biostatistics (CRAB)

175 patients in each arm End points

• Oncologic Non Inferiority – PFS at 2 yrs

• Perioperative Outcomes • Improved functional recovery with RARC ?

• QOL and Costs

How did Open Radical Cystectomy (ORC) evolve ?

155 patients with bladder cancer undergoing radical cystectomy from 1955 -1971 Operative mortality went down from overall 8% to 2% in the last 50 cases

1955-1971 , 5 yr OS 20-40% for pT2-T3

1971-1997 , 5 yr OS 60-85% for pT2-T3

Open Radical Cystectomy

• Time to present perioperative results and oncologic outcomes

• 5 decades • Is Open Radical Cystectomy always of

high quality ?

Is ORC always of high quality ?

Herr et al JCO 2004 Konety et al J Urol 2003 Hedgepeth RC et al , Urology 2011

SWOG 8710 268 Radical Cystectomies

SEER 1988-96 , 1923 Radical Cystectomies

4472 patients undergoing Open RC - SEER 1992 -2005

Open ≠ Better • SWOG 8710 No LND – 9% , Limited sampling – 37% Only 50% had 10 or > LN Positive SM 10% , LR 15% • SEER Study ( 1992 -2005) No LND – 40% LN yield < 10 – 36% • SEER Study (1988-96) No LND – 30% LN yield < 10 - 78%

Take Home Message • RARC is not superior in terms of decreasing

perioperative morbidity except blood loss • RARC and ORC have similar HRQOL outcomes • Significant increase in utlization of RARC • RARC more expensive • Intracorporeal diversion feasible but challenging

with no clear benefits – RCT needed

Take Home Message

• Critical to train current and future workforce in BOTH approaches following sound oncologic principles

Take Home Message

Most Important

• Patient outcome

• Surgeon Skill

Least Important

• Surgeon Ego/Bias

• Marketing /Hype

Thank You