1. Can We Preserve The Bladder In Muscle Invasive Bladder Cancer?
Dr Manish Patel
Urological Cancer Surgeon
Westmead Hospital
University of Sydney

2. The Outcomes of Radical Cystectomy
Outcomes of RC are very good.
Recurrences occur:
Median 12 months
86% of recurrences occur in first 3 years.
Local only recurrence more likley in OC.
Most series- any recurrence= death.
Even with LN+ve disease, 30% likelihood of long term survival.
Stein et.al. Journal of Clinical Oncology, Vol 19, No 3 (February 1), 2001: pp

3. Upstaging is common with Bladder Cancer
Based on TURBT, EUA, CT
MRI with dynamic contrast enhancement and Fe particles may be better.
Ureteric obstruction- 67%-90% >pT2 (Skinner et,al,1998)
Muscle invasive bladder cancer (cT2) is upstaged to pT3 in:
52% (Soloway et.al.1994)
78% (Pagano et.al.1991)
41% (Frazier et.al.1992)
Most cT2 bladder cancers are pT3 or higher.
Occult LN mets increase with increasing P stage
P0, Pa, Pis, P1: 5%
P2: %
P3-4: 45%

4. Quality of Life After RC is Good.
There are a number of QoL instruments for bladder cancer.
Very few reports on QoL after BC treatment.
Lack of baseline measurements.
Lack of longitudinal measurements.
No comparison of RC vs Bladder Preservation.
Only on prospective QoL study (SF-36) (Hardt et.al)
Physical functioning decreased pre-post-op (80 to 68)
Pain, health perception, vitality, social functioning, general well being, satisfaction with life all the same as pre-op at one year.

5. Options of Bladder Preservation with Muscle Invasive BC
TURBT alone
Partial Cystectomy alone
External Beam Radiation Alone
Brachytherapy
Neoadjuvant Chemo and TURBT
Neoadjuvant Chemo and Partial cystectomy
Multimodality therapy

6. Does a delay in cystectomy Result in lower survival?
Randomised studies of immediate cystectomy vs XRT and salvage cystectomy.
Study
Randomised groups
Survival
MD Andersen (n=67)
Immediate XRT+cystectomy
5yrs: 45%
XRT and salvage cystectomy
5yrs: 22%
Urologic Co-operative Group UK (n=187)
Immediate cystectomy
5 yrs: 39%
XRT with salvage surgery
5 yrs: 29%
Danish National Bladder Group (n=187)
5 yrs: 23%
Possibly: Need low threshold for salvage cystectomy

7. TURBT Author Protocol Survival Cystectomy rate Barnes (n=85) G1/2 T2
TURBT X1
27% 5 yrs
Henry (n=43)
Favourable (small T2) TURBT X1
77% 5 yrs
25%
Solsona (n=59)
Negative cytology and rpt biopsy
yrs
19%
Herr (n=45)
Negative rpt TUR and cytology
5 yrs
24%
TURBT is feasible for selected T2 bladder tumours.
Not for dome or high posterior wall

8. Partial Cystectomy MSKCC study (contemporary) 85 patients with T2
OS: 5yrs
74% alive with bladder intact
67% alive with NED bladder intact
7 pts sup recurrence
15 pts advanced recurrence
75% false negative frozen section margins.
80% of positive margins suffered advanced recurrence.
Selection:
Dome/post wall/diverticulum

9. Partial Cystectomy Candidates: CR or PR to Neoadjuvant chemo
Solitary lesions in favoyrable locations
No CIS
Good bladder capacity.

10. Radiation TURBT and 65 Gy XRT
Study
Patient no.
Survival (5 yr%) T2 T3
Fossa et.al.
308 38 14
Davidson et.al
709 49 28
Gospodarowicz
355 50 32
Goffinet et.al.
384 42 35
TURBT and 65 Gy XRT
Tumour debulking (TURBT may be most important)
Assessment of response at 40Gy may be useful
CR to XRT- will have a good outcome.
60% invasive recurrence rate. Approx 50% cystectomy rate.
Co-existant CIS: High recurrence rate in bladder (70%).
Squamous differentiation may have poorer outcome

11. Radiation-Complications
Early complications
Diarrhea
Bladder irritation (particularly if trigonal cancers)
Late complications (2-3 years later)
Worse if heavily pretreated (TURBTS, BCG etc)
Radiation cystitis (heamturia, frequency contracted bladder)
Radiation proctitis (persistent diarrhea, rectal bleeding)
Sexual dysfunction (60%)
Tumour Recurrence
Invasive – salvage cystectomy
Superficial- as per normal protocols

12. Neoadjuvant and Partial cystectomy
Neoadjuvant chemotherapy (X3-4 cycles) followed by TURBT staging.
Then followed by partial cystectomy and pelvic lymph node dissection.
Herr et.al (n=26). No Pt was eligible for PC alone.
19 had P0
7 yr median FU: 65% alive
54% with bladder
18% invasive recurrence
26% superficial recurrence
PC is a valid option in suitable patients, even with T3 tumours that are small.

13. Neoadjuvant and TURBT Neoadjuvant chemo (3-4 cycles). Restaging TURBT.
Stenberg et.al (n=71). T2-T4a
Median 54 months FU: 71% alive
57% bladder intact
After chemo: P0 or superficial disease, 5yr survival = 71%
Invasive disease 29%
MSKCC (n=111)
60(54%) achieved T0 status.- Most preserved bladders
56% recurrence in bladder (30% invasive)
25% of T0 is not P0.

14. Neoadjuvant chemotherapy and TURBT
Srougi et.al. (n=30)
TURBT, MVACX3.
PR or no response > cystectomy (n=12)
CR > all retained their bladder (n=14)
5 yrs, 71% (10) had local recurrences.
8 had radical cystectomy
Survival of all CR pts was 5yrs.
All patients need close observation because of inadequate staging and occurrence of new tumours.

15. Trimodality Therapy Maximal TURBT XRT Concurrent chemotherapy Rational
Cisplatin, 5-FU and paclitaxel sensitise tumour tissues to XRT.
Increase cell kill in a synergisitic fashion.
Also high (25%-50%) chance of micro-metastatic disease at presentation.

16. Trimodality Therapy
Does the radiation add anything, as XRT outcomes are similar to TURBT outcomes?
Series
Treatment
5 yr survival
5 yr survival with bladder
TURBT, XRT and concurrent Chemotherapy.
Dunst (n=79)
TURBT, cisplatin, XRT
52%
41%
RTOG 1993 (n=42)
Cisplatin and XRT
42%
Kachnic (n=106)
TURBT, MCV and XRT
43%
RTOG 1997 (n=123)
49%
38%
TURBT and Chemotherapy alone
Given (n=93)
TURBT and MCV
51%
18%
Srougi (n=30)
Partial C and MVAC
53%
20%
It appears that concurrent chemo/XRT does add something.

17. Shipley- Massachusetts General Protocol
Hydronephrosis, Poor renal function Irritable bladder, Low Capacity T4a/4b, CIS
If no, Maximal TURBT
If yes, For surgery
No Significant
Tumour Remaining
Bulky
Tumour Remaining
Chemo/ XRT
Protocol-Induction
CE 4 weeks after induction
Radical
Cystectomy
CR, consolidation
Chemoradiation
Residual Cancer

18. MGH- Chemoradiation Protocol
Induction
2 cycles of neoadjuvant MCV
Methotrexate, cisplatin, vinblastine
Concurrent cisplatin and 40Gy XRT
Consolidation chemoradiation
Further 24Gy XRT
Cisplatin based chemotherapy

19. MGH- Results Patients selected for Trimodality therapy (n=190)
Denominator unknown
Induction chemotherapy
29 (15%) had residual disease > RC
40 (21%) unable to tolerate ChemoRad > RC
121 (64%) went on to have consolidation Chemoradiation.
After 4 years median FU
86 (45%) alive with NED
110 (58%) still had a bladder.
Overall 5 yrs 54%

20. RTOG bladder sparing protocols
All tumours are small.
All tumours are able to be maximally resected.
These are not the same tumours in cystectomy series.
All patients are healthy with good ECOG status
All patients were eligible for cystectomy.

21. Clinical Preictors of Outcome
Stage (cT2=62%, cT3=47%)
Hydronephrosis (CR= 37% vs 68%)
CR on induction chemoradiation
Quality of Life
Cystectomy for bladder contracture (2-7%)
On going urinary symptoms
Women-19% incontinence
Reduced urinary compliance in 22%
Bowel symptoms- 22%
Sexual dysfunction

22. Concerns with Bladder sparing therapy
Need for complete TURBT (visibly clear)
CR 77% vs 54% for visble and not visible complete resection.
Survival 52% vs 5 yrs
Urothelial cancer change
Those with CR to trimodality will develop
20-30% new or recurrent bladder tumor
Occur median of 2.1 years and mainly CIS
Ultimately 1/3 of recurrence need late cystectomy.
Pelvic recurrence
12%
Delay in cystectomy
Limited diversion alternatives.

23. Is Bladder Preservation Equivalent to Radical Cystectomy?
No but!
Viable alternative for Pts wanting to preserve bladder
Only small likely decrease in survival
But
Not all patients are suitable
50% will ultimately have cystectomy
Diversion choices will be limited.
Operation more difficult and complications higher.
Not evidence that quality of life is actually better.
A number of pts will have significant bladder and bowel symptoms.