1. Minimally Invasive Approaches in the Treatment of Urothelial Carcinoma “Robotic Radical Cystectomy” Douglas S. Scherr, M.D. Weill Medical College of Cornell University

2. Robotics Beyond The Prostate Radical Cystectomy Can we achieve equal oncological outcome?

3. Radical Cystectomy Gold Standard for Invasive Disease Role in T1 Disease Quality of surgery impacts outcome and survival

4. Was the Effect all Chemotherapy? Are surgical variables important? Post cystectomy survival predicted by: a.) age b.) stage c.) node status d.) negative surgical margins e.) >10 nodes removed Hazard ratio for death: a.) 2.7 for + surgical margin b.) 2.0 for <10 nodes removed Herr et al. JCO, 22(14): 2781, 2004

5. 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 80% 75% 74% 51% Stein et al., J Clin Oncol, 19(3): 666-75, 2001 Recurrence Free Survival Overall Survival 5 Year 10 Year 81% 80% 72% 56%

6. Early Vs. Late Cystectomy 90 pts who had TUR + BCG ultimately underwent cystectomy 41/90 had T1 disease Median Follow up of 96 mos Early cystectomy ( 2 years): 56% survival Herr and Sogani, J Urol, 166: 1296-9, 2001

7. 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, 1936 Jewett et al. J Urol, 55: 366, 1946

8. 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

9. 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 LND b.) 12.7% of LND had <4 nodes removed Lymph node density (# pos nodes/total # nodes) Konety et al. J Urol, 170: 1765, 2003

10. IMA Genitofemoral nerve Genitofemoral nerve Aortic Nodes Common Iliac Nodes Hypogastric and Obturator Nodes Extent of Pelvic Lymph Node Dissection

11. Survival By Number Of Lymph Nodes Removed Herr et al. JCO, 22(14): 2781, 2004

12. Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004 Postcystectomy survival by node status and number of nodes removed

13. Post Cystectomy Survival VariableHR*95% CIP Value Treatment RC v MVAC + RC10.7 to 1.40.97 Age ≥65 v < 65 years1.51.0 to 3.60.03 pT stage 3-4 v 0–22.31.5 to 3.60.0002 Node status positive v negative1.61.0 to 2.50.04 Margins Positive v negative2.71.5 to 4.90.0007 Nodes removed < 10 v ≥1021.4 to 2.80.0001 Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004

14. Gold Standard Open radical cystectomy (RC) is the gold standard for treatment of muscle-invasive bladder cancer.

15. 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

16. 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

17. 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) 31:719 Basillote JB et al: J Urol (2004) 172:489 Taylor GD et al: J Urol (2004) 172:1291 Galich A et al: JSLS (2006) 10:145 Rhee JJ et al: BJU Int (2006) 98:1059

18. Comparison of Surgical Techniques However, direct comparison between open and minimally invasive RC of early oncologic parameters is lacking. Lymph node yield Lymph node yield Margin status Margin status

19. Study Comparison Comparison of perioperative and early pathologic outcomes in a consecutive series of open and robotic RCs at our institution.

20. Methods 100 consecutive patients underwent RC by a single surgeon at our institution 2006- 2007 22 open 22 open 78 robotic 78 robotic

21. 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

23. 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

24. Results: Patient Characteristics There was no difference in the following parameters among the 2 cohorts. Age Age BMI BMI ASA class ASA class Prior abdominal surgery Prior abdominal surgery Prior abdominal radiation Prior abdominal radiation Neoadjuvant chemotherapy Neoadjuvant chemotherapy

25. Results: Clinical Stage Open (n=22)Robotic (n=78)P-value Clinical Stage ≥ T271%49%0.06 < T2 29%51%

26. Urinary Diversion OpenRoboticP-value Urinary Diversion0.4 Ileal conduit52%53%0.2 Indiana pouch24% 9%0.1 Orthotopic neobladder 24%38%0.1

27. Operative Time OpenRoboticP-value Median operative time, minutes (range) 300 (165 – 540) 390 (210 – 570) 0.03* Ileal conduit270 (165 – 510) 300 (210 – 450) 0.4 Indiana pouch300 (300 – 540) 440 (390 – 480) 0.2 Orthotopic neobladder390 (330 – 456) 480 (390 – 570) 0.01* * P < 0.05

28. Robotic Learning Curve Initial casesLast 16 cases P-value Robotic operative time (minutes) Median4503380.002* Range300 – 570210 - 510 * P < 0.05

29. Blood Loss & Postoperative Parameters OpenRoboticP-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

30. Postoperative Complications OpenRoboticP-value Overall complications24%21% 0.3 Minor Prolonged ileus1 (5%)4 (12%)0.3 Major4 (19%)3 (9%)0.2 Conversion to open--1 (3%) Enterocutaneous fistula0 (0%)1 (3%) Percutaneous drainage of abscess 1 (5%)1 (3%) Wound dehiscence1 (5%)0 (0%) Respiratory failure1 (5%)0 (0%) Myocardial infarction1 (5%)0 (0%)

31. Pathologic Stage OpenRoboticP-value Pathologic stage0.3 pT010%22% pTa0%6% pTis19%28% pT15%6% pT210%9% pT324%22% pT433%6% Organ confined, < pT3 43%72%0.03* Non-organ confined, pT3-4 57%28% * P < 0.05

32. Node & Margin Status OpenRoboticP-value Node status N057%81%0.04* N+34%19% Lymph node yield (total ± SD) 18.9 ± 8.817.4 ± 8.30.6 Positive surgical margins 8%2% 0.2 * P < 0.05

33. Cost Results Urinary DiversionOpenRobotic Ileal 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

34. 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)

35. 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)

36. Conclusions: Robotic Cystectomy Decreased –Blood loss –Transfusion requirement –Time to regular diet –Length of hospital stay

37. 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: 35 Herr H et al: J Urol (2004) 171: 1823

38. Minimally Invasive Cystectomy Minimally Invasive = Cancer Sparing

39. Future Directions Prostate Sparing? Improved Diagnostics

40. 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 continence b.) No episodes of retention c.) 82% maintained potency Vallancien et al. J Urol, 168: 2413, 2002

41. 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

42. Multiphoton Images

43. Multiphoton Images