Role of Bladder -Preserving Approach in The Treatment of Muscle Invasive TCC

1. Role of Bladder-Preserving ApproachinThe Treatment of Muscle Invasive TCC

2. Introduction Bladder cancer is a serious threat to life. TCC is the most common bladder tumor. For the yr 2000 (in US): 53,200 new cases 12,200 deaths

3. Introduction TCC at the initial presentation. • 70% of TCC are superficial • Tumor recurrence is 50-70% • 10-30% of those will progress to invasive disease. • 30% of TCC are muscle invasive • More than ½ of them expected to develop metz = 12,000 death/yr in the US = 50 –100 / 1,000,000

4. Introduction Treatment of invasive TCC • Aggressive therapy is warranted to control the disease. • This shouldn’t obscure the need for reasonable quality of life. • In North America, main local management of muscle-invasive TCC remains radical cystectomy with urinary diversion.

5. Introduction • This approach is undergoing transition. • Organ-preserving approaches have been successfully applied to the management of several types of cancer • Clearly play an important role in the management of ms invasive TCC.

6. Introduction • Ideally, trt of invasive TCC aims to: • Eliminate the primary tumor. • Assure long term survival & quality of life. • Maintain normally functioning bladder. • In elderly or pts likely to die of other causes local control may be all what is needed. • So, reaching those goals & preserving the bladder may appear to be attractive option. • In minimal surgery, post op complications can be limited.

7. Introduction Cystectomy & its Price for a Gold Stander • Major operation • Complication • Acknowledged mortality(although low). • 2.3% • 10-15% overall complication rate • Higher (20-30%) for orthotopic reconstruction. • (220 pt Amling, J urol, 1994)

8. Introduction Treatment Options • Radical Cystectomy • TURBT or Partial cystectomy alone • Radical TUR + Systemic chemo • Radiation: Interstitial or External Beam • Multimodality therapy

9. Treatment Options • Radical Cystectomy • TURBT or Partial cystectomy alone • Radical TUR + Systemic chemo • Radiation: Interstitial or External Beam • Multimodality therapy

10. TURBT alone • The main use today of TURBT alone, in muscle invasion, is mainly in its diagnostic role. • It’s use in trt carries the concerns of recurrence & progression. • Nevertheless, several studies showed that in selected pts TUR could have therapeutic value. How this idea came up as a treatment option? Feneley, Sem in Uro Onco, 2000

11. TURBT alone • 10-17% of post TURBT cystectomies showed pT0. • TCC frequently affect elderly

12. TURBT alone Technique • Radical TUR • Tumor resection to cancer-free margin, requires complete resection of all macroscopic tumor through the bladder wall to extravesical connective tissue. Feneley, Sem in Uro Onco, 2000

13. TURBT alone Concerns: • Feasibility to: • Adequately staged • Adequately resection of the tu • Field changes Laufer, Sem in Uro Onco, 2000

14. TURBT alone Limitations: • In 662 TURs, systematic bx were done from the base, sides & adjacent margins • 35% (232) showed residual tu • 84% (195) were invasive Residual noted in solid (76%) > papillary (21.5%) This can be solved by selection criteria Kolozsy, Br J Urol, 1991

15. TURBT alone Study • 133 pts • w invasive TCC bladder • treated by radical TUR • who had (–ve) bx of the ms layer of the tumor bed. • F/U > 5 years for all subjects > 10 years 44.4% Solsona; J urol, 1998

16. TURBT alone • control gr • 76 patients with invasive pathological stage pT2-3a, N0-3 • treated by cystectomy. Solsona; J urol, 1998

17. Comparison of results between: gr 1 (59 pts f/u > 10 yrs) and gr 2 (74 pts f/u > 5 yrs)

18. Superficial bl or upper tract Or prostatic mucosa Or CIS requiring cystectomy • Progression was concentrated in the first 3 years (75.6%). • In 3 patients disease progressed at > 5 years (65, 71 & 92 mo) • None in f/u of > 10 yrs. Comparison of results between: gr 1 (59 pts f/u > 10 yrs) and gr 2 (74 pts f/u > 5 yrs)

19. 35 (26.3%) 18 (30.5%) 37 (27.8%) 20 (34%) Followup of entire series • In more details

20. TURBT alone Followup • At 5 & 10 yrs of f/u • cause specific survival rates were 80.5 and 74.5%, • bl preservation rates were 82.7 and 79.6%, • 44.4% alive & free • 36% died free from dis • 23.7% alive & free • 50.8% died free from dis

21. No significant difference in cause specific survival, with the control group Comparison of cause specific survival of all patients (cT2-3a, N0) and controls (pT2-3a, N0-3).

22. TURBT alone Another Study • 217 pt • 79% not candidate for TUR, but for radical or partial • 21% (45 pt) TUR candidate. • F/U for median of 5.1 yrs • Overall survival = 82% (37/45 pt) • 67% (30/45 pt) w functioning Bl • 9 free • 21 required repeated superficial TUR w or w/o BCG Herr; urol clinic, 1992

23. TURBT alone Exclusion Criteria >T2b Wide spread CIS Multiple TCC >3 cm +ve TCC at the tumor’s bed on 2nd TUR Herr; urol clinic, 1992

24. TURBT alone Exclusion Criteria Other studies reported less favorable outcome But didn’t follow rigid selection criteria. >T2b Wide spread CIS Multiple TCC >3 cm +ve TCC at the tumor’s bed on 2nd TUR Herr; urol clinic, 1992

25. TURBT alone Final Comments: • No randomized trials comparing it w other options like Radical or multi modality. • In view of the tolerability of current radiation +/- chemo, the role fro TUR alone diminished. • Probably useful in selected case w: small T2, + elderly pt + Not candidate for Radiation +/- chemo Laufer, Sem in Uro Onco, 2000

26. Partial Cystectomy • Advantages • full-thickness resection • adequate margins. • LN sampling • Resect inaccessible tu through TUR • In diverticulum, dome, over ureteral orifice. • Drawback • Risk of intravesical recurrence • Risk of extravesical recurrence • decline in more contemporary series to 0% Laufer, Sem in Uro Onco, 2000

27. Partial Cystectomy Selection Criteria • Solitary • Location (usually upper ½, or 5cm) • Amenable to complete resection w free margins • Absence of CIS • Size • Should allow complete resection w/o affecting bl. function. • No > 50% should be removed Dandekar, J Surg Oncol, 1995

28. Partial Cystectomy Outcome Local recurrence rate: 38-78% Sweeny, uro clin, 1992

29. Partial Cystectomy Outcome Laufer, Sem in Uro Onco, 2000 • In a review of series from the last 40 yrs: • 5 yrs survival: • T230- 100% • T3a 16- 88% • T3b 0 - 45% • Dandekar, J Surg Oncol, 1995 • 20 TCC • 5 T2a, 18T2b, 9 T3 • More to the higher • Overall actuarial survial = 80.1% at 5 yrs • Barrilero, Actas Urol Esp - 1997 • 45 pts T2 or higher, • f/u = 9-258 mo • Partial cystectomy alone. • 21 cases showed bladder relapse • Survival even better • But this is a highly selected gr

30. Analysis of 300 cystectomies in the Univ of California LA The results looks the same Overall survival (Surv) of patients treated w cystectomy for bladder cancer stratified by pathological stage Those with N0 stratified by pathological stage. DALBAGNI, J OF UROL, 2001

31. Partial Cystectomy Final Comments • It should be noted that • Rigid pt selection  good long-term result w partial cystectomy alone, • Only suitable for 10% of the pt Dandekar, J Surg Oncol, 1995

32. No randomized trials comparing partial w Radical or multimodal bladder-preserving options. Partial Cystectomy Final Comments Laufer, Sem in Uro Onco, 2000 • No properly designed study have determine long-term result of partial. • It should be limited to pt w CI to Radical.

33. Introduction Treatment Options • Radical Cystectomy • TURBT or Partial cystectomy alone • Radical TUR + Systemic chemo • Radiation: Interstitial or External Beam • Multimodality therapy

34. Radical TUR + Systemic Chemo • Rationale • Experience with systemic chemo indicate some improvement of the local control. • In 1982, • Socquet reported a favorable result in 25 pt using Methotrexate w folinic a. post partial cystec. for T3a.

35. Radical TUR + Systemic Chemo Study • Collaborative N. of England gr. • treated 61 pts w T2/3 but used: • Radical TUR • X4 chemo (Methotrexate) • Repeated cysto/ TUR • If tu persist  conventional trt Robert, Clinical Mgt of Bl CA, 1999

36. Radical TUR + Systemic Chemo • Of the 61 pts: • 17 (28%) had persistent tu • 15 (25%) developed recurrent invasive tu • at median of 18 mo • Treated by radical cysto or radiation • 15 (25%) recurrent superficial tu • Overall 29/61 (48%) remain free of invasive tu Robert, Clinical Mgt of Bl CA, 1999

37. Radical TUR + Systemic Chemo • This same gr (Collaborative N. of England gr) added cisplatin to methotrexate (55 pts) and the whole population of 116 pt published recently: • Median f/u 11.6 yrs (4-15yrs) • 13 yrs for the old gr of methotrexate + folinic a • 8 yrs for the combination gr Robert, Clinical Mgt of Bl CA, 1999

38. Radical TUR + Systemic Chemo • Most tu were < 5 cm • Only 13% were T2 (the rest were higher) • Random bx were not taken • ?CIS status is not known • 17 pt in the combination gr had adjacent CIS • Most pts in this series had G3 (78.4%) With all these potential –ve factors, what was the outcome? Robert, Clinical Mgt of Bl CA, 1999

39. Radical TUR + Systemic Chemo • The actuarial disease-specific survival • For the 1st gr • 2, 5, 10 yrs • 69%, 39%, 33% • For the 2nd gr • 82%, 70%, 61% • Only 28% of pts w combination trt required cystectomy or radiotherapy The results in this selected population compare favorably w conventional trt Robert, Clinical Mgt of Bl CA, 1999

40. Radical TUR + Systemic Chemo • Similarly good results reproduced in other centers in Europe • Many published in BJU from 1991-1997 • They also used MVAC, CMV, 5FU, • In the MSKCC tried neoadj MVAC in 32 pt w 75% preserving their bladder in a median f/u of 19 months Feneley, Sem in Uro Onco, 2000

41. Radical TUR + Systemic Chemo In conclusion • The results discussed of the combination chemo + conservative surgery suggest that the approach should be tested in a randomized comparison w more conventional approaches

42. Introduction Treatment Options • Radical Cystectomy • TURBT or Partial cystectomy alone • Radical TUR + Systemic chemo • Radiation: Interstitial or External Beam • Multimodality therapy

43. Radiation Therapy • In several European centers, the combination of external beam and interstitial radiotherapy is standard trt in a selected group w muscle-infiltrating TCC. Wijnmaalen, Sem in Uro Onco, 2000

44. Radiation Therapy • In Rotterdam: • Initially, Radium needles • Later, cesium-containing needles.

45. Radiation Therapy Interstitial radiation • Advantages: • High local dose to the tu in short time. • Less toxicity to the surrounding tissue. • Never became widely used due to: • Modern technique of Ex Beam RT. • Advancement of anesthesia & surgery time. • But in several European ctrs IRT • further developed & • remain the standerd for selected pts Wijnmaalen, Sem in Uro Onco, 2000

46. Radiation Therapy IRT • Almost exclusively in Europe. • Only 2 small series published in USA. • Criteria of IRT: • Solitary • <5cm • No LN or distal metz • Pt condition should permit surgery

47. Radiation Therapy Afterload: • The afterload technique 1st reported in 1969. • Adopted in 1989 in France • Radio active material is introduced post op • Less exposure to the personnel

48. Steps of the combination EBRT + IRT • TUR or partial • Low EBRT (11 Gy) + high IRT (50 Gy) • Or high EBRT (30-40 Gy) + high IRT (30 Gy) Wijnmaalen, Sem Uro Onc, 2000

49. EBRT + IRT Results: • Summery of six published studies; • 5 yrs of: • Local control= 64- 88% • Relapse rate 11-36% • Distant metz 14-24% • Actuarial overall survival= 47-66% • Disease-free survival= 62%-81%, Wijnmaalen, Sem Uro Onc, 2000

50. EBRT + IRT Results • MR= 1.5-3% • Wound complication were not uncommon • Generally resolved by conservative mgt. • Necrosis at the area of the tu in 14-20% • Causes no complaints in most pts • Transient. • Ureteral stenosis was reported by some. Wijnmaalen, Sem Uro Onc, 2000