1. Diagnosis and Management of
Bladder Cancer

2. Gold standards in bladder cancer
diagnosis
• Cytology
• Cystocopy plus biopsy

3. staging classification (UICC 1997) - primary tumour
superficial muscle-invasive
(papillary) (solid)
urothelium
lamina propria
superficial muscle
deep muscle
pTa
pT1
CIS
pT2a
pT2b
pT3
perivesical
periureteral
perirenal
fat
Diagnosis and Management in Urology 6th
September 2010

4. Management of Bladder TCC
- Superficial Disease -
risk of progression treatment
low ( 2 - 11%) TUR-BT
-unifocal, pTa G1/2 +/- intravesical chemotherapy
intermediate ( 29 - 39%) TUR-BT + intravesical
-multifocal pTa, pT1 G1/2, chemo- / immunotherapy
recurrences
high ( 40 - 83%) TUR-BT + intravesical
-CIS, pTa/1G3 chemo- / immunotherapy
radical cystectomy
radiation therapy

5. Tumour
Bladder Wall
Prostate
Cystoscope
Transurethral resection of the bladder
TURB
Diagnosis and Management in Urology 6th
September 2010

6. Non- Surgical Management of
Bladder Cancer

7. CASE HISTORY 1
• 51 yo barman
• 1 episode frank haematuria
• No past Hx
• Smoker, 20/d x 30y

8. CASE HISTORY 1
• Investigations:
– FBC, U+E
– MSU for C+S
– IVU
– Cystoscopy + Biopsy

9. CASE HISTORY 1
• Bladder lesion seen at cystoscopy
• Biopsy: Grade 3 TCC, pT1
– But no muscle in sample
• Next step?

10. CASE HISTORY 1
• TURBT
• Tumour resected
– pT2a (at least)
• Staging investigations?

14. Treatment Options Localised Muscle
Invasive Bladder Cancer
• Radical Cystoprostatectomy
+/- Neo adjuvant chemotherapy
• Radical Radiotherapy
+/- Neo adjuvant chemotherapy

15. Multi-Disciplinary Team Meeting
• Surgeons, Oncologists, Radiologists,
Pathologists, Nurses
• Treatment options discussed

16. Radiotherapy Versus Surgery
FOR
• Organ Preservation
• Sexual Function
• No anaesthetic
• Suitable for less fit
patients
Against
• No randomised data
• Less pathological
information

17. CASE HISTORY 1
• Patient opted for radical radiotherapy with
neo-adjuvant chemotherapy

18. Neo-Adjuvant Chemotherapy
Neo-Adjuvant Chemotherapy Definitive Treatment
Surgery/Radiotherapy
Rationale: Down-staging, micro-metastatic disease control,
radiosensitising

19. Why chemotherapy in invasive bladder
cancer?
• 5 yr survival only 50%
• Pattern of recurrence usually distant mets
rather than local recurrence
• Suggests treatment failure mainly due to
presence of occult metastatic disease present
at the time of definitive local treatment, with
20-30% of patients failing locally

20. Chemotherapy
• Cisplatin initially was the most active single
agent used
• As single agent, response rates only 10-30%
• Combination chemotherapy centred around
Cisplatin was studied in RCT’s in 1990’s & shown
to have ↑ response rates & ↑ OS

21. Combination Chemotherapy
• Methotrexate,Vinblastine,Doxorubicin and
Cisplatin (M-VAC) had been the gold standard
until recently
• Limited greatly by toxicity-up to 63% of
patients may require dose-reduction
• Long term survival benefit is modest-median
survival consistently less than 13 months

22. Gemcitabine-Cisplatin
• Randomized phase III trial comparing standard
M-VAC with Gemcitabine/Cisplatin
• Patients were stage T4b or any N/any M TCC
bladder with no previous chemotherapy
• 405 pts enrolled

23. M-VAC Gem/Cis
No. of patients 202 203
Overall RR 46 49
Complete RR 12 12
Median Survival 14.8 13.8
Rx related dths 3% 1%
Neut. Sepsis 12% 1%
G3-4 mucositis 22% 1%
Mucositis/Cycle 3.6 days 0.5 days

24. Advantages & Disadvantages of Neo-
adjuvant Chemotherapy
• Improved drug delivery
before possible interference
caused by local treatments
• Better tolerability &
compliance due to improved
PS
• Immediate Rx of micro-mets
• Prognostic information by
observing response to
chemotherapy
• May allow bladder
preservation in complete
responders
• Delayed definitive Rx
• Toxicity & possible
lowering of PS before local
treatment
• Difficult to assess
response in primary
• Possibility of inaccurate
clinical staging before
treatment
• May treat some patients
unnecessarily

25. Bladder Chemotherapy -Common Side-
Effects
• Neutropenia
• Anaemia
• Alopecia
• Nausea and Vomiting
• Peripheral nerve damage
• Renal impairment
• Mucositis

26. Case 1: Patient Management
• Completed 3 cycles of Gemcitabine-Cisplatin
Chemotherapy
• Cystoscopy: complete response
• Plan Proceed to Radiotherapy

27. Radical Radiotherapy
• CT planned volume
– bladder empty

28. Radiotherapy
• Radiotherapy
delivered by Linear
Accelerators
• Usually one treatment
(fraction) per day for
6-8 weeks

29. Contouring on multiple CT slices – typically 40 slices

32. Radiotherapy
• Treated supine with 3 field arrangement
– Anterior,R lateral wedged,& L lateral wedged fields
• 64 Gy / 32 F/ 6.5 wks

33. Radiotherapy
Acute Side Effects
• Diarrhoea
• Proctitis- Urgency, PR bleeding, Mucous Discharge
• Dysuria
• Frequency
• Urgency
• Tiredness

34. Radiotherapy
Late Side Effects
• Reduced bladder capacity
• Reduced erectile function
• Rectal bleeding
• Altered bowel habit
• Second cancer risk

35. CASE 1
• Tolerated treatment well
• Alive and well 18 months later, cystoscopy
clear

36. CASE HISTORY 2
• 45yr old plumber.
• September 2004
• 1 year history of recurrent macroscopic
haematuria, unresponsive to antibiotic
therapy.

37. CASE HISTORY 2
• Cystoscopy
– Tumour at the left ureteric orifice.
• Histology
– Grade 3 Transitional cell carcinoma.
– Muscle invasive.

38. CASE HISTORY 2
• Pre-operative CT
– Tumour at the left side of bladder with left
hydronephrosis
– Small pelvic nodes and two small equivocal
pulmonary nodules

39. CASE HISTORY 2
• Cystectomy
– Frozen section of 2 pelvic nodes
• Positive for metastatic TCC
• pT2b N2 …… M1?
• Referred to oncology

40. CASE HISTORY 2

41. Symptoms of Lung Metastases
• Symptoms?

42. Bladder Metastases
• Other sites of metastases:
– Nodes
– Liver
– Brain
– Bone
– Skin

43. Treatment Options
• Chemotherapy
– Gemcitabine + Cisplatin
• Radiotherapy for pain/bleeding

44. Gemcitabine Cisplatin
• Cycle 1-3 well tolerated.
– 2 Lung lesions had remained stable but 2 new
3mm lung lesions found.
– No other disease
• Proceed with Cycle 4-6.
– Stable disease

45. INDEPENDENT PROGNOSTIC FACTORS
• KPS
– >80 MS 18.5
– <80 MS 10.5
• VISCERAL METASTASIS
– YES MS 11.1
– NO MS 22.3

46. CASE HISTORY 2
• Stopped chemotherapy July 05
– Pursued an active fitness program
• Returned 3mths later – asymptomatic
• Repeat CT requested for Jan 06
– Progression in the lung lesions

47. Gemcitabine Cisplatin
• Returned February to start chemo
• Cycle 1-3 (7-9)
– Lesions improved
• Cycle 4-6 (10-12)
– Further improvement
• September 2006 - Stopped chemotherapy

48. CASE HISTORY 2
• October 2006 - Attended GP
– Numbness in Left Arm for 1½ minute associated
with confusion
• Urgent CT brain

49. CASE HISTORY 2

50. MRI

51. WBRT
• Oct 06- 30Gy 10fractions 2weeks
• April 07- RIP

52. WBRT
– Neurological improvement 50-70%
– Improved survival 3-6mths vs BSC
– Surgery or Stereotactic radiosurgery
• 80% will have CNS relapse.
– WBRT following Sx or SRS
• 20% will have CNS relapse.
Lancet 2004, 363 1665-1672
J Uro 1993, 149, 480-483

53. CONCLUSION
• Organ preservation is possible with
radiotherapy
• Neo-Adjuvant Chemotherapy improves
outcome
• Chemotherapy provides excellent palliation in
metastatic bladder cancer
• Radiotherapy is useful for palliation of bladder
cancer symptoms