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Minimally Invasive Approaches in the Treatment of Urothelial
Carcinoma
“Robotic Radical Cystectomy”
Douglas S. Scherr, M.D.
Weill Medical College of Cornell University
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Robotics Beyond The Prostate
• Radical Cystectomy
• Can we achieve equal oncological outcome?
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Radical Cystectomy
• Gold Standard for Invasive Disease
• Role in T1 Disease
• Quality of surgery impacts outcome and survival
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Was the Effect all Chemotherapy?Are surgical variables important?
• Post cystectomy survival predicted by:a.) ageb.) stagec.) node statusd.) negative surgical marginse.) >10 nodes removed
• Hazard ratio for death:a.) 2.7 for + surgical marginb.) 2.0 for <10 nodes removed
Herr et al. JCO, 22(14): 2781, 2004
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Radical Cystectomy for T1 TCC
• USC Experience: 208 pts with T1 disease
• USC Experience with T2 disease
Recurrence Free Survival Overall Survival
5 Year 10 Year 5 Year 10 Year
80% 75% 74% 51%
Stein et al., J Clin Oncol, 19(3): 666-75, 2001
Recurrence Free Survival Overall Survival
5 Year 10 Year 5 Year 10 Year
81% 80% 72% 56%
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Early Vs. Late Cystectomy
• 90 pts who had TUR + BCG ultimately underwent cystectomy
• 41/90 had T1 disease
• Median Follow up of 96 mosEarly cystectomy (<2 years): 92% survivalLate cystectomy (>2 years): 56% survival
Herr and Sogani, J Urol, 166: 1296-9, 2001
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Extent of Lymphadenectomy
• Is there more to the node dissection than staging?
• 1936 Colston and Leadbetter performed studies on 98 cadavers “limited metastatic disease was restricted to the pelvic nodes”
• 1946 – Dr. Jewett “cardinal site of metastasis”
Colston and Leadbetter, J Urol, 36: 669, 1936Jewett et al. J Urol, 55: 366, 1946
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Extent of Lymphadenectomy
• Node positive patients can enjoy long term survival
• 24% of grossly node positive disease survived 10 years without adjuvant therapy
• More nodes removed correlates with improved survival
Sanderson et al. Urol Oncol., 22: 205, 2004
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Extent of Lymphadenectomy
• Likely no staging advantage to extending the node dissection above the aortic bifurcation
• 33% of unsuspected nodes found at common iliacs
• Practice patterns vary widely:a.) 40% of cystectomies have no LNDb.) 12.7% of LND had <4 nodes removed
Lymph node density (# pos nodes/total # nodes)
Konety et al. J Urol, 170: 1765, 2003
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IMA
Genitofemoralnerve
Genitofemoralnerve Aortic
Nodes
Common Iliac Nodes
Hypogastric and Obturator Nodes
Extent of Pelvic Lymph Node Dissection
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Survival By Number Of Lymph Nodes Removed
Herr et al. JCO, 22(14): 2781, 2004
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Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004
Postcystectomy survival by node status and number of nodes removed
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Post Cystectomy Survival
Variable HR* 95% CI P Value
Treatment RC v MVAC + RC 1 0.7 to 1.4 0.97
Age ≥65 v < 65 years 1.5 1.0 to 3.6 0.03
pT stage 3-4 v 0–2 2.3 1.5 to 3.6 0.0002
Node status positive v negative 1.6 1.0 to 2.5 0.04
Margins Positive v negative 2.7 1.5 to 4.9 0.0007
Nodes removed < 10 v ≥10 2 1.4 to 2.8 0.0001
Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004
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Gold Standard
• Open radical cystectomy (RC) is the gold standard for treatment of muscle-invasive bladder cancer.
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Minimally Invasive Bladder Cancer Surgery
• Efforts to reduce the operative morbidity of RC have fostered interest in minimally invasive approaches.
• Laparoscopic RC• Robot-assisted laparoscopic RC
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Concerns of Robotic Cystectomy?
• Concerns regarding minimally invasive RC
– Absence of long term oncologic outcomes– Absence of long term functional outcomes – Limited pelvic lymphadenectomy– Longer operative time– Increased cost
Miller NL et al: World J Urol (2006) 24:180
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Outcome Measures of Minimally Invasive Bladder Surgery
• Previous reports comparing open versus minimally invasive RC have focused on perioperative outcomes.
– Blood loss– Operative time– Analgesic requirement– Time to regular diet– Length of hospital stay
Hemal AK et al: Urol Clin N Am (2004) 31:719Basillote JB et al: J Urol (2004) 172:489Taylor GD et al: J Urol (2004) 172:1291Galich A et al: JSLS (2006) 10:145Rhee JJ et al: BJU Int (2006) 98:1059
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Comparison of Surgical Techniques
• However, direct comparison between open and minimally invasive RC of early oncologic parameters is lacking.
• Lymph node yieldLymph node yield
• Margin statusMargin status
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Study Comparison
• Comparison of perioperative and early pathologic outcomes in a consecutive series of open and robotic RCs at our institution.
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Methods
• 100 consecutive patients underwent RC by a single surgeon at our institution 2006-2007
• 22 open22 open• 78 robotic78 robotic
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Technique
• Posterior dissection
• Isolation of ureters
• Lateral dissection
• Control of bladder pedicles
• Anterior dissection
• Control of DVC and division of urethra
• Control of prostate pedicles and nerve-sparing
• Pelvic lymph node dissection– External iliac, hypogastric, and obturator lymphadenectomy up to the level
of the mid-common iliac vessels
• Extracorporeal urinary diversion through a 5-7cm midline incision– Orthotopic neobladder: robot re-docked for urethral neovesical
anastomosis
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Data Collection and Analysis
• Data was collected prospectively– Patient characteristics– Perioperative outcomes– Early pathologic outcomes
• Data analysis– Chi-square test– Fisher’s exact test– Student’s t-test
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Results: Patient Characteristics
• There was no difference in the following parameters among the 2 cohorts.
• Age Age • BMI BMI • ASA classASA class• Prior abdominal surgeryPrior abdominal surgery• Prior abdominal radiationPrior abdominal radiation• Neoadjuvant chemotherapyNeoadjuvant chemotherapy
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Results: Clinical Stage
Open (n=22) Robotic (n=78) P-value
Clinical Stage
≥ T2 71% 49% 0.06
< T2 29% 51%
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Urinary Diversion
Open Robotic P-value
Urinary Diversion 0.4
Ileal conduit 52% 53% 0.2
Indiana pouch 24% 9% 0.1
Orthotopic neobladder 24% 38% 0.1
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Operative Time
Open Robotic P-value
Median operative time, minutes (range)
300(165 – 540)
390(210 – 570)
0.03*
Ileal conduit 270(165 – 510)
300(210 – 450)
0.4
Indiana pouch 300(300 – 540)
440(390 – 480)
0.2
Orthotopic neobladder 390(330 – 456)
480(390 – 570)
0.01*
* P < 0.05
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Robotic Learning Curve
Initial cases Last 16 cases P-value
Robotic operative time (minutes)
Median 450 338 0.002*
Range 300 – 570 210 - 510
* P < 0.05
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Blood Loss & Postoperative Parameters
Open Robotic P-value
Median estimated blood loss, mL (range)
750(250 – 2500)
400(100 – 1200)
0.002*
Median blood transfusions, units PRBCs (range)
2 (0 – 7) 0.5 (0 – 3) 0.007*
Median time to regular diet, days (range)
5 (4 – 8) 4 (3 – 6) 0.002*
Median length of stay, days (range)
8 (5 – 28) 5 (4 – 18) 0.007*
* P < 0.05
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Postoperative Complications
Open Robotic P-value
Overall complications 24% 21% 0.3
Minor
Prolonged ileus 1 (5%) 4 (12%) 0.3
Major 4 (19%) 3 (9%) 0.2
Conversion to open -- 1 (3%)
Enterocutaneous fistula 0 (0%) 1 (3%)
Percutaneous
drainage of abscess
1 (5%) 1 (3%)
Wound dehiscence 1 (5%) 0 (0%)
Respiratory failure 1 (5%) 0 (0%)
Myocardial infarction 1 (5%) 0 (0%)
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Pathologic StageOpen Robotic P-value
Pathologic stage 0.3
pT0 10% 22%
pTa 0% 6%
pTis 19% 28%
pT1 5% 6%
pT2 10% 9%
pT3 24% 22%
pT4 33% 6%
Organ confined, < pT3 43% 72% 0.03*
Non-organ confined, pT3-4 57% 28%* P < 0.05
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Node & Margin Status
Open Robotic P-value
Node status
N0 57% 81% 0.04*
N+ 34% 19%
Lymph node yield
(total ± SD)
18.9 ± 8.8 17.4 ± 8.3 0.6
Positive surgical
margins
8% 2% 0.2
* P < 0.05
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Cost Results
Urinary Diversion Open RoboticIleal conduit $154,276 $90,472
Direct $98,445 $79,015
Indirect $55,831 $11,457
Continent cutaneous diversion
$155,222 $105,203
Direct $138,925 $90,245
Indirect $16,297 $14,958
Neobladder $120,601 $111,111
Direct $96,820 $72,843
Indirect $24,321 $38,267
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Cost Conclusions
• Robotic cystectomy appears more cost-effective than open cystectomy for treatment of bladder cancer– Majority of improvement driven by lower LOS– High initial materials cost of robotic surgery defrayed by
subsequent cost savings during hospitalization
• Annual robotic volume does not need to be high (<25 cases per year) to justify use of robotic cystectomy
• Cost savings of robotic cystectomy however is diminished with decreased open cystectomy LOS (2 to 9 days)
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Conclusions:Robotic Cystectomy
• Increased operative time– significantly longer operative time in the
robotic neobladder cohort (p=0.01)
• Decreased operative time with increased experience – 450 to 338 min (p=0.007)
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Conclusions:Robotic Cystectomy
• Decreased
– Blood loss– Transfusion requirement– Time to regular diet– Length of hospital stay
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Conclusions:Robotic Cystectomy
• Equivalent lymph node yield– 17.4 (robotic) vs. 18.9 (open), p=0.6
• Equivalent margin rate– 2% (robotic) vs. 8% (open), p=0.2
• Long term oncologic and functional outcomes are required
Stein JP et al: J Urol (2003) 170: 35Herr H et al: J Urol (2004) 171: 1823
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Minimally Invasive Cystectomy
• Minimally Invasive = Cancer Sparing
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Future Directions
• Prostate Sparing?
• Improved Diagnostics
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Prostate Sparing Cystectomy
• Role for improved continence and potency
• Need to rule out prostate cancer or TCC of prostatic urethra
• Functional Results are good:a.) 97% complete continenceb.) No episodes of retentionc.) 82% maintained potency
Vallancien et al. J Urol, 168: 2413, 2002
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Prostate Sparing Cystectomy
• Incidence of Pca is 30-50% with approx. 48% are clinically significant
• 60% of CaP involve the apex (79% significant and 42% insignificant)
• 48% of prostates had urothelial ca involvement of which 33% had apical involvement
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Multiphoton Images
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Multiphoton Images