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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
Robotics Beyond The Prostate
• Radical Cystectomy
• Can we achieve equal oncological outcome?
Radical Cystectomy
• Gold Standard for Invasive Disease
• Role in T1 Disease
• Quality of surgery impacts outcome and survival
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
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%
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
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
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
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
IMA
Genitofemoralnerve
Genitofemoralnerve Aortic
Nodes
Common Iliac Nodes
Hypogastric and Obturator Nodes
Extent of Pelvic Lymph Node Dissection
Survival By Number Of Lymph Nodes Removed
Herr et al. JCO, 22(14): 2781, 2004
Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004
Postcystectomy survival by node status and number of nodes removed
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
Gold Standard
• Open radical cystectomy (RC) is the gold standard for treatment of muscle-invasive bladder cancer.
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
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
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
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
Study Comparison
• Comparison of perioperative and early pathologic outcomes in a consecutive series of open and robotic RCs at our institution.
Methods
• 100 consecutive patients underwent RC by a single surgeon at our institution 2006-2007
• 22 open22 open• 78 robotic78 robotic
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
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
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
Results: Clinical Stage
Open (n=22) Robotic (n=78) P-value
Clinical Stage
≥ T2 71% 49% 0.06
< T2 29% 51%
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
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
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
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
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%)
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
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
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
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)
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)
Conclusions:Robotic Cystectomy
• Decreased
– Blood loss– Transfusion requirement– Time to regular diet– Length of hospital stay
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
Minimally Invasive Cystectomy
• Minimally Invasive = Cancer Sparing
Future Directions
• Prostate Sparing?
• Improved Diagnostics
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
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
Multiphoton Images
Multiphoton Images