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