Ca Urinary Bladder Management

1. CA URINARY BLADDER - STAGING & MANAGMENT
PRESENTER- DR. JASMEET SINGH TUTEJA
MODERATOR- PROF. RAJEEV GUPTA

2. STAGING- 8TH EDITION

5. WORK-UP
• CBC, RFT, LFT
• Urine cytology and cystoscopy
• CT/MRI of abdomen and pelvis, ideally prior to biopsy.
• Perform Transurethral resection of bladder tumor
(TURBT) and EUA.
• Image of upper urinary tract (CT/MRI urography, intravenous
pyelogram, renal US, retrograde pyelogram or ureteroscopy) if
biopsy proven malignancy .
• Chest X-ray
BIOPSY SPECIMEN SHOULD CONTAIN MUSCLE FOR PROPER STAGING
OF TUMOR.

6. CYSTOSCOPY
• It provides direct visualization of the bladder
and facilitates biopsy of the bladder.
• The number, size,shape, and location of
tumors as well as appearance of the
surrounding mucosa, urethra and ureteral
orifice are documented.
Urinary cytology
•Gold standard for non invasive screening of
bladder cancer.
• Sensitivity: 40-60%
• Specificity: 98%

7. INTRAVENOUS UROGRAPHY
Traditionally it was modality of
choice in evaluating the disease
Largely replaced by CT Urography
Only 60% bladder cancer are
detected by IVP.
Tumors appear as sessile or
pedunculated filling defect

8. ULTRASONOGRAPHY
Focal or hypoechoic or mixed
echogenicity non mobile mass
projecting into bladder lumen
No posterior shadowing
Focal bladder wall thickening
Color Doppler shows increase
vascularity

9. CT ABDOMEN AND PELVIS
• It is not sensitive in describing the
depth of invasion or lymph node
involvement but it can be helpful in
determining extravesical extension
and planning in subsequent
treatment.

10. MRI IMAGING
• Gadolinium – enhanced MRI
studies may prove useful in
distinguishing superficial from
invasive disease intravesical
from extra vesical tumors
• MRI might be particularly useful
in detecting early nodal
metastasis.

11. MANAGEMENT
• NMIBC (non muscle invasive bladder cancer )
• Tis, Ta, T1
• MIBC (muscle invasive bladder cancer)
• T2 onwards, N1
• Metastatic cases
• M1

12. TURBT

13. TURBT- NMIBC scoring
• LOW RISK
– Tumor <3 cm
– Grade 1 disease
– T1a with e/o CIS
– 15% chance of Recu.
– 0.2 % risk of progression
• HIGH RISK
– Stage Ta or T1
– Grade III
– CIS
– 61% recurrence risk
– 17% progression risk.
• INTERMEDIATE RISK
• Multiple grade 1 tumours
• Multiple grade II tumours,
stage Ta
• Single grade II, stage T1
• 38% chance of
recurrence
• 5% risk of progression

14. • Observation :
• Completely resected
• Ta
• Grade 1
• No abnormal cytology in urine cytology
• Indications of Adjuvant therapy
• CIS associated with Ta or T1 tumours
• Any grade G3 tumour
• Multifocal tumours
• Rapidly recurring after TURBT
• Urothelial carcinoma involving the prostatic
mucosa or ducts

15. • BCG : live attenuated strain of mycobacterium
– MOA: triggers inflammatory cascade, inducing
neutrophil and Th1 chemotaxis
– Reconstituted with 50 ml of saline and
administered through urethral catheter
– Treatment begin 2-4 wks after tumour resection
– After instillation the patient should retain the solution
for 2 hours.

16. • Schedule
– Induction
• Weekly for 6 wks intravesically
• Cystoscopy with urine cytology and possible biopsy should be done to
confirm the recurrence or progression at 3 months
– Maintenance
• SWOG regimen of 3 weekly instillations at 3, 6 and every 6 months
for 3 years
• All guidelines and meta analysis recommend at least one year
of BCG maintenance therapy
• Complete remission is obtained in up to 70 % of cases
• If cytology and biopsiesremain positive, another cycle may produce an
additional 15% complete remission.

18. OTHER AGENTS (INTRAVESICAL)
Chemotherapeutic Agent MOA
Mitomycin C Antibiotic; inhibits DNA synthesis
Thiotepa Alkylating agent; cross links nucleic acids
Doxorubicin/ Valrubicin Topoisomerase inhibitors; intercalating agents;
inhibit DNA synthesis
Immunotherapy MOA
BCG T-helper type 1 immune response
Interferon (With BCG) Activates T-helper type 1 immune response

20. • Cystectomy in NMIBC
– Ta Low or intermediate risk disease– if bladder sparing
modalities have failed
– In a high risk patient with multiple recurrent tumours or
T1 tumours with associated CIS, LVI, or variant
histologies
– In a high risk patient with persistent or recurrent
disease with one year following treatment with two
induction cycles of BCG or BCG maintenance.
• NO ROLE OF RT IN NMIBC

21. MIBC
TREATMENT OPTIONS
RADICAL
CYSTECTOMY
WITH URINARY
RECONSTRUCTIO
N
BLADDER PRESERVATION
PROTOCOLS
RELAPSE OR
PROGRESSION
• If left untreated 85%patient may die within 2 yrs
• NO diff in OS, cause specific survival and distant recurrence free
survival

22. SURGERY- Radical Cystectomy
• Indication:
• Muscle invasive or locally advanced disease T2-T4a
• Non muscle invasive bladder cancer
T1G3 with high risk features ( multiple, recurrent ,large ,CIS)
Refractory or failure to cystoscopy resection and intravesical
chemotherapy or immunotherapy
Non compliance to intravesical chemotherapy or immunotherapy
Extensive disease not amenable to cystoscopy resection .
 Histological variants : squamous cell carcinoma , adenocarcinoma and
sarcomatoid or spindle cell carcinoma
 Palliation for pain, bleeding or urinary frequency
5 ys OS after RC is 60% for T2 and 40% for T3-T4a

23. Diagram showing boundaries of pelvic
lymphadenectomy

24. • CYSTECTOMY NOT BE DONE :
– LN metastases are unresectable because of bulk or
proximal extent above the common iliac vessels
– There is evidence of extensive peri-ureteral disease
– The bladder is fixed to the pelvic sidewall or
– Tumour is invading the recto sigmoid colon.
• LYMPHADENECTOMY
– Include : obturator , hypogastric, presciatic,
presacral lymph nodes.
– Minimum 15 lymph nodes should be removed

25. NEO ADJUVANT THERAPY
• RADIOTHERAPY
– Preoperative radiotherapy has not shown to improve survival.
– Preoperative radiotherapy for operable MIBC can result in
tumour down staging after 4-6 wks.
• CHEMOTHERAPY
– Neo-adjuvant chemotherapy is recommended for T2- T4a,
cN0M0 bladder cancer
– Recommended use of three cycles of Cisplatin based
combination chemotherapy. Specifically M-VAC or CMV or
gemcitabine cisplatin

26. • Platinum-based combination
chemotherapy 5% absolute
benefit at 5 years ( overall
survival increased from 45% to
50%).
• This effect was observed
irrespective of the type of local
treatment, and did not vary
between subgroups of patients

27. ADJUVANT THERAPY
• CHEMOTHERAPY
– NCCN recommends adjuvant chemo if Neo-adjuvant chemo was not
given.
– Indications:
• T3 or more
• Node positive
• Positive Margins
• Lymph node positive patients benefit more than lymph node negative in
terms of DFS.
• Beneficial role of Cisplatin based adjuvant chemo in MIBC.

28. • Adjuvant Radiotherapy
– No strong supporting RT in the adjuvant setting.
– May be given in cases of high risk for loco-regional relapse.
• Positive surgical margins
• Tumour spillage
• pLN positive
• Inadequate Lymph node dissection <10
• Post-operative radiation is indicated in the setting of positive
surgical margin after partial cystectomy.
– Rationale: decreases probability of tumor recurrence
following radical cystectomy.
Dose:
Areas at risk for harbouring residual microscopic
disease - 45 to 50.4 Gy EBRT.

29. Bladder Conservation approach
• 2 main concerns about bladder preservation compared with radical cystectomy
• Toxicity of radiation therapy on bladder function
• Field cancerization effect :
• 30-50% of patients experience a local recurrence (~50% invasive and ~50%
superficial), either in the area of tumor or in a different part of bladder
• If bladder preservation is selected, close surveillance is critical
• No trials have till date directly compared Cystectomy and
Bladder-preservation

30. BLADDER PaRESERVATION STRATEGIES
• CONSERVATIVE STRATEGY
– Partial Cystectomy
– TURBT
– Radical EBRT +/- Brachytherapy boost.
• Combined modality treatment
– Chemo + TURBT/Partial cystectomy
– Tri-modality : Maximal TURBT, Chemotherapy and
Radiotherapy.

31. • Partial Cystectomy
• Local recurrence rates range from 38 to 78%
• Rarely performed.
• TURBT alone is usually not sufficient for MIBC.
CONSERVATIVE SURGERY

32. • EBRT
– Factors having significant favourable effect on local
control with radiotherapy
• Early clinical stage (T2 and T3a)
• Absence of ureteral obstruction
• Visibly complete TURBT
• Small tumour size (<5cm) solitary, papillary/ sessile absence of
coexisting carcinoma in situ.

33. EBRT +/- Brachytherapy Boost
• Brachytherapy is another technique to deliver a higher dose of
radiation to a limited area of the bladder within a short period.
• Reserved for patients with solitary bladder tumors
• Part of combined modality therapy with TURBT and EBRT as well
as interstitial radiation therapy.
• EBRT doses of 30 Gy + implant tumour dose of 40 Gy
• Patients with solitary clinical stage T2 to T3a tumors >5 cm, local
control rates at 5 to 10 years range from 72% to 84%.

34. ROLE OF RADIOTHERAPY
• CIS, Ta, T1 - No role for radiotherapy
• T2-T4aN0M0 - Potential role for radiotherapy, combined with
synchronous chemotherapy if patient sufficiently fit
• TanyN1–3M0 or TanyNanyM1 - Radical radiotherapy has no
role . Palliative intent only with systemic chemotherapy.

35. • Trimodality therapy (TURBT+CHEMO+RT)
– Ideal candidate
• Primary T2-T3a tumours that are unifocal
• Tumour size less than 5 cm in maximum diameter
• Tumour not associated with extensive CIS
• No presence of ureteral obstruction or tumour associated
hydroureteronephrosis.
• Good capacity of the bladder
• Visibly complete TURBT
• Adequate renal function to allow Cisplatin to be given
concurrently with irradiation.

36. • Continuous course
paradigm
• Split course
paradigm

37. RADIOTHERAPY PLANNING
• Phase 1-
– The whole pelvis , encompassing the pelvic lymph nodes,
bladder and proximal urethra.
– Elective irradiation of the pelvic lymph nodes.
• Phase 2-
– Then cone down to boost the bladder alone.
PHASE 1:Dose:40-45 GY @ 1.8-2Gy/#
BOOST PHASE: Dose:10-15Gy to entire bladder and upto 66 Gy to
tumor.(aim bladder receive 60 Gy)
OR
treat the bladder+tumor with a 2-cm margin to a total dose of 66 Gy

38. SIMULATION
• CT Simulation preferred
• Patient Position :supine with arms on chest.
• Immobilization :knee and ankle rest
• Bowel preparation: rectum should be empty.
• Bladder preparation: empty bladder prior to scan.
• All planning and treatment should be carried out with the bladder empty
To minimize the risk of geographic miss
To keep the treated volumes as small as possible
• The scan is performed with 3-5 mm slices from the lower border of L5 to
the inferior border of the ischial tuberosities.

40. • BOOST- Bladder + margin 1.5-2 cm
• PHASE 1:Dose:40-45 GY @ 1.8-2Gy/#
BOOST PHASE: Dose:10-15Gy to entire bladder and upto 66 Gy to
tumor.(aim bladder receive 60 Gy)
OR
treat the bladder+tumor with a 2-cm margin to a total dose of 66 Gy
• Dose : 60-66 Gy to bladder

41. FILED ARANGEMENTS

42. • Contouring guidelines
– GTV : primary tumour
– CTV : whole bladder and any extra-vesicle extension
– Men : entire prostate
– Women : the proximal 2 cm of urethra is also
considered s apart of target field
– PTV : 1.5-2 cm around CTV

44. NODAL DELINEATION

45. 3DCRT IN CA BLADDER

46. TOXICITY
• Acute effects
– Dysuria
– Urgency
– Frequency
– Diarrhea
• Chronic effects
– Cystitis
– Hemorrhagic cystitis
– Bladder contracture
– Rectal stricture
– Small bowel
obstruction.
79 % of patients have normal bladder function at 10 yrs

47. RT IN RECURRENCE AFTER CYSTECTOMY
• Proximal urethral recurrence with CRT 65- 70Gy.
• For pelvic sidewall recurrences, the dose are limited by the
presence of small bowel in the field.
• Still radiation with concurrent Cisplatin can be given to doses
tolerated by the intestine, ileal loop and stoma, usually 50-
60Gy.

48. PALLIATIVE RT
• Haematuria
• For rapid pain relief.
• Painful bony metastasis
• Dose 30Gy/10#/2wks or 8Gy single # or
20Gy/5#/1wk.
• Palliation to inoperable patients, when not suitable for
chemotherapy.

49. Metastatic Bladder Cancer
• The prognosis of metastatic bladder cancer, is poor, with a median survival
on the order of only 12 months.
• Nevertheless, platinum-containing agents have significant antitumor effect,
there has been great interest in the use of chemotherapy for advanced
disease.
• Gem/cis is prefered over MVAC due to higher toxicity in MVAC group.

52. SUMMARY

54. FOR MIBC

55. RADIOTHERAPY
• Concurrent chemo-radiation as a part of multimodality
bladder sparing protocol in T2- T4N0M0.
• Radical RT in inoperable cases.
• Neo adjuvant radiotherapy
• Adjuvant radiotherapy
• Pelvic recurrence after radical cystectomy.
• Palliative Radiotherapy for metastatic disease.

56. THANK YOU