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Clare Grant
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6 A Personal History NIH CWRU U of TN U of Miami

7 Animal Model for Bladder Cancer Carcinogen induced FANFT

8 Three Models Primary tumors individual tumors, simulates clinical scenario of locally advanced cancer Transplanted tumor rapid screen, like metastatic tumor Implantation in the bladder also simulates clinical situation

9 Title: Chemotherapy of an experimental transitional cell carcinoma Authors: DeKernion, J.B., Soloway, M.S., Persky, L. Citation: Urol 4:63-68 Year Published: 1974

13 Title: Susceptibility of urothelium to neoplastic cellular implantation Authors: Weldon, T.E. and Soloway, M.S. Citation: Urol 5: Year Published: 1975

14 Title: Prophylaxis of bladder tumor implantation - intravesical and systemic chemotherapy Authors: Soloway, M.S. and Martino, C. Citation: Urol 79:29-34 Year Published: 1976

15 Title: Rationale for intensive intravesical chemotherapy for superficial bladder cancer Authors: Soloway, M.S. Citation: J Urol 123: Year Published: 1980

16 TUR Bladder Tumor

17 My Perception Little Data Wide variability in skill of this common operation Little emphasis on technique Consider the number of articles on RP, lap nephrectomy, vs. TUR of bladder tumor Lack of guidelines on what constitutes adequate resection

18 TUR BT Are They Complete Retrospective review of UM referrals (MSS) All to OR within 4 wks of TURBT for Ta T1 33/47 (70%) had incomplete resection 10 macroscopic at main site 23 tumor at another location

19 Complete TUR BT? 16/23 (69%) with initial T1 had residual TCC 17/24 (70%) Ta All locations

20 Second TUR BT AUA Berdjis et al, Germany 140 consecutuve Ta, T1, CIS 35% residual TCC 60% if multifocal Attending vs trainee no difference

23 TUR BT Height of the irrigant Do not overfill bladder (50%) Select right angle or bladder wall loop Judge stage Cold cup or loop resection Decide on depth of resection Retrieve material in strainer

30 Office Cautery Prior low grade Ta Small volume Patient acceptance No systemic medication

33 Prostatic Urethra Patients with CIS Multifocal and recurrent HG Ta or T1 Cytology positive without obvious tumor

34 C. Hargett HG T1 + PU

38 A. Rosenfeld 75 yo man, CABG 1990, 40 pack/yrs 2006 LG Ta TCC 11/08 HG T1 nested variant TCC 12/08 retur BT HG Ta, small focus, m.p. OK

42 Hexvix cystoscopy Hexvix increases detection of patients with CIS lesions by 28% * *Jichlinski et al J Urol 2003

43 Detection endpoint, PC B305/04 PP # Pts with pathology 352 # Pts with Ta/T1 278 (79%) # Ta/T1 pts with 1 more 47 (16.9%) Ta/T1 with Hexvix 99% CI: p-value: Hexvix significantly improves Ta/T1 detection (per ITT and PP) 43

44 Patients with 1 lesions detected with Hexvix compared to white light 50 % 45 % 40 % 35 % 30 % 25 % 46 % 39 % 20 % 15 % 10 % 5 % 16 % 13 % 0 % Ta (262 pts) T1 (63 pts) CIS (41 pts) Dysplasia (106 pts) Hexvix detects more lesions of all types 44

45 Detection of CIS In Hexvix group: # Pts with CIS 41 # CIS patients detected with Hexvix 13 (32%) and not with WL 45

46 False positive detection rate # lesions # false positives (%) Hexvix (B) (12.1%) White light (B) (10.6%) White light (A) (9.8%) False positive rate similar for Hexvix and White Light 46

47 PC B305 Recurrence 47

48 Bladder cancer history PC B305/04 ITT Hexvix White Light Initial BC 149 (40.8%) 152 (42.1%) Recurrent BC 216 (59.2%) 209 (57.9%) The two groups are comparable 48

49 9 months recurrence PC B305/04 # Ta/T1 9 mts Rec PP Hexvix (36%) p= White Light (46%) Use of Hexvix detection leads to a significant reduction in 9 months recurrrence 49

50 9 months recurrence, Patients with Initial versus recurrent BC Hexvix (n=200) White Light (n=202) # Pts # Rec % # Pts # Rec % Relative reduction Total Initial Recurrent Recurrence is higher in pts with recurrent than initial BC Recurrence is reduced in both patients with initial and recurrenct BC 50

52 Benefits of Seeing the Histology Get to know your pathologist Does your pathologist have subspecialty training in GU? Grading system Cautery artefact Depth of invasion Extent of tumor focal or substantial

53 Radical cystectomy for BCG failure: has the timing improved? U of Miami Single Surgeon

54 Introduction If cystectomy is performed before progression to muscle invasion (<pt2), as is the case when BCG is first initiated, the cancer specific survival is over 90 %.

55 U of Miami (MSS) 5 year estimated overall survival: 65% 5 year estimated diseasespecific survival: 69% 11 patients (12%) N+ 17 patients (19%) died of bladder cancer

56 Methods Retrospective analysis of our RC database ( ) Analyze patients who underwent RC after BCG

57 Methods RC from (group 1) RC from (group 2) Pathologic stage and survival compared.

58 Results 1993 to 2007: 445 patients underwent RC by a single surgical team. 168 (38%) had BCG prior to RC. 152 met the inclusion criteria. (75 group 1 & 77 group 2).

59 Both groups were similar in Results Baseline demographics T-stage prior to BCG initiation BCG cycles received Time interval from initiation to RC.

60 Characteristics Results Group 1 ( ) N(%) Group 2 ( ) N(%) N Age (yr ± SD) at BCG therapy 68.5± ± at RC 70.5±9.5 68± Male/Female 55/20 64/ Smoking Yes 54(72) 48(62.5) 0.4 No 16(21) 20(26) Unknown 5(7) 9(11.5) ct-stage (BCG initiation) Ta 16 (21.5) 26 (34) 0.23 T1 40(53.5) 34(44) CIS 19(25) 17(22) P

61 Results There was no change in the proportion of patients undergoing RC with <T2 BC in recent years. 52% in groups 1 and 43% in group 2 had progressed to muscle invasive BC (p=0.5)

62 Results Comparison of Pathologic stage at RC and survival. Characteristic Group 1(%) Group 2(%) P <T2 36(48) 44(57) 0.5 T2 15(20) 13(17) >T2 24(32) 20(26) N+ 12(16%) 8(11%) yr Overall Survival 68±8 60±6 (Events) (Log rank)

63 DSS

64 Summary With careful review of cancer risk factors believe the balance is in favor of initial bladder preservation Requires: re-tur to pta or pt0, BCG, cytology and cysto monitoring RC for any high grade new tumor, no second intravesical treatments, unless prohibitive surgical candidate

65 Eliminate The Term Superficial Bladder Cancer As used it includes: Ta, low grade Ta, high grade CIS T1

66 These Are Superficial Tumors

71 Superficial Bladder Cancer Implies good prognosis May suggest low grade Patient friendly (as opposed to invasive) To most implies no invasion Perpetuates concept that lamina propria invasion is not a relatively aggressive cancer

72 Cancer Staging The purpose of staging cancer is to communicate the prognosis of a given tumor Superficial adds no information regarding a tumors prognosis Pathologists do not use the term superficial BC

73 Superficial Lying on, not penetrating below, or affecting only the surface. A tumor which invades the lamina propria should not be termed superficial since it is not confined to the surface Merriam-Webster's Collegiate Dictionary, 10th Edition, 1999.

74 Editorial #1 J. Urology 175: , 2006 Nieder, A. and Soloway, M.S. Eliminate the Term Superficial Bladder Cancer

75 Editorial #2 It s time to abandon the superficial in bladder cancer Mark S. Soloway European Urology 52: 2007

76 Prostate or Bladder Cancer?

77 Prostate Bladder

78 Bladder Cancer What % present with T2 or greater? 56% of men 80% of women Approximately 40% will die of BC Early detection is best hope for improvement

79 Contrast BC and PC Pts diagnosed with low stage PC > BC Public awareness PC >>BC Available and used marker PC >>>BC Patients seek testing PC >>>BC

ICUD 2011 Recommendations. Bladder Cancer

ICUD 2011 Recommendations. Bladder Cancer ICUD 2011 Recommendations Bladder Cancer ICUD Bladder Cancer 2011 Chair Mark Soloway Co chair Henk van der Poel Committee Chairs A. Kamat/P. Hegarty M. Amin/V. Reuter P. Karakiewicz/S. Shariat B. Konety/W.