Overview of Management of Carcinoma Urinary Bladder

2. MANAGEMENT OF CARCINOMA
URINARY BLADDER
Presenter-Dr. Manas Dubey
Department of Radiation Oncology
HBCH ,Varanasi
1ST June 2019

3. ANATOMY OF URINARY BLADDER
The bladder is a hollow, muscular organ situated in the pelvis .

4. Contd….
The mucosal lining of the bladder comprises a transitional epithelium that
extends from the renal pelvis to the urethra.
The most common tumors arising in the urinary system are transition cell
(or urothelial) carcinomas (TCC or UC).

5. LYMPHATIC DRAINAGE OF BLADDER

6. World (GLOBOCAN 2018)
 Bladder cancer is the tenth most common cancer
worldwide
 Men - 4.5% of all cancers
 Women - 1.5% of all new cancers
 For both sexes- 3.1% of all cancers
In India,
According to National Cancer Registry Programme, the overall incidence
rate of the urinary bladder cancer is 2.25% (per 100,000 annually): 3.67%
among males and 0.83% for females.
EPIDEMIOLOGY

7. Contd….
 Median age at diagnosis is above 70 years.
 Survival rates are poor, 5 years survival- 45% (muscle-
invasive cancer)

8. Unfortunately He lost the Battle

9. Natural History
Non-muscle-invasive bladder cancer
 70% to 80% present with non-muscle-invasive bladder cancer
(NMIBC, stage Ta, T1, and carcinoma in situ [Tis])
NMIBC shows a high recurrence rate of 50% to 70% after
treatment by transurethral resection of the
bladder tumor (TURBT)
10% to 20% of patients with NMIBC, the disease progresses to
muscle invasion (≥T2 lesions).

10. ETIOLOGY
Three categories
1) Gene abnormalities
(2) Chemical exposure,
(3) Chronic irritation
Perez 6th edition.

11. CONT (Gene Abnormalities)…

12. Contd…
Chemical Exposure Chronic irritants
Aromatic amines, aniline
dyes, and nitrites and nitrates
catheters, recurrent urinary track
infections, Schistosoma haematobium,
and irradiation
Tobacco use (Cigarette)- 3 fold increase
risk.
S. haematobium infestation results in an
increased risk of squamous cell
Chemicals, plastics, coal, tar, and
and aristolochic acid,

13.  90%-transitional cell carcinoma-
 5%- squamous cell carcinoma
 5%-others-small cell carcinoma
-adenocarcinoma (urachal remnant)
-melanoma
-carcinosarcoma
Pathology

14.  Painless, hematuria-intermittent (80-90%)
 Urinary frequency due to irritation or reduced bladder capacity
 Urinary tract infection
 Pain in advanced lesions.
Perez 6th edition.
Clinical Features

15.  Detailed history
 Complete blood count
 Liver function test, Kidney function test
 Prostate specific antigen
 Urine cytological examination
Work Up
Perez 6th edition.

16. Contd…
Flexible cystoscopy- pretreatment planning and biopsy of lesion to assess pathology,
grade, and depth of invasion

17. PURPOSE-
 STAGING AND DIAGNOSIS
 THERAPEUTIC
 GOLD STANDARD FOR DIAGNOSIS
FOR STAGING-
 Adequate resection with muscle in specimen
Perez 6th edition.

20.  Transurethral resection of bladder tumor (TURBT) for
- complete resection of superficial bladder tumors
- deep biopsy to assess for muscle-invasive tumors.
 Biopsy is performed in all suspicious-looking lesions

21. COMPUTED TOMOGRAPHY
-Abdomen, pelvis and
chest
-For perivesical fat
invasion
-sensitivity-85%
-specificity-94%
-flat lesions,carcinoma
In situ, tumors <1 cm
are falsely negative.
Gunderson and Tepper clinical radiation
oncology4th ed.

22. -accuracy for T staging- 75-92%
-accuracy for lymph node staging-70-90%
Magnetic resonance imaging-invasion of adjacent organs and T
staging
MAGNETIC RESONANCE IMAGING
Gunderson and Tepper clinical
radiation oncology4th ed.

23. STAGING

29. Treatment

30. Contd…
NMIBC (non muscle invasive bladder cancer )
• Tis, Ta, T1
MIBC (muscle invasive bladder cancer)
• T2 onwards, N1
Metastatic cases
• M1

31. NMIBC
 Aim :
• prevent recurrence
• Disease progression to a life threatening stage
 Modality
• TURBT standard of care
• Adjuvant intra vesicle therapy – immunotherapy/
chemotherapy

32. CONTD…
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
HIGH RISK
– Stage Ta or T1
– Grade III
– CIS
– 61% recurrence risk
– 17% progression risk.
LOW RISK
– Tumor <3 cm
– Grade 1 disease
– T1a with NO e/o CIS
– 15% chance of Recu.
– 0.2 % risk of progression
Perez 6th edition.

33. NCCN 2019 Ver 3.0

35. CONTD….
LOW RISK
TURBT is mostly curative.
Cystoscopy to be done after 3months followed by
9months followed by yearly.
INTERMEDIATE & HIGH RISK-
TURBT to be followed by intravesical therapy 9wks.
If no residual patient kept on BCG maintenance and
surveillance.

36. CONTD….
 Schedule
 Induction
• BCG 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 BCG
 All guidelines and meta analysis recommend at least 1-3 year
of BCG maintenance therapy
 Complete remission is obtained in up to 70 % of cases

38. Muscle invasive carcinoma
bladder (MIBC)

39. TREATMENT OPTIONS
Muscle-invading TCC bladder
(If left untreated 85%patient may die within 2 yrs)
Cystectomy
BLADDER
CONSERVATION
PROTOCOLS
RELAPSE OR PROGRESSION

40. SURGICAL APPROACHES

41. Radical Cystectomy
 Rationale For Radical Cystectomy
 lowest local recurrences.
good long-term survival rates.
provides accurate pathologic staging for determining the need
for adjuvant therapy
morbidity and mortality of radical cystectomy has substantially
improved over the past decades

42. Radical Cystectomy
Radical cystectomy with pelvic lymphadenectomy
is considered the standard of care.
 Includes perivesicular fat and urethra
 In women, the anterior wall of the vagina, the ovary and the
uterus are also taken
In men, the prostate and seminal vesicles are taken
Bladder reconstruction : Neo Bladder or Ileal Conduit
Timing of surgergy- Within 3 months of TURBT.
Removal of more than 15 lymph nodes has been postulated.

43. Contd…
 Delay of treatment beyond 90 days of primary diagnosis causes
 significant increase in extravesical disease (81 vs. 52%)
 From Stein series incidence of L.N metastasis:
Overall estimate ~ 25% patient undergo cystectomy have
LN mets
• pTis, pTa, pT1: 5%
• pT2 : 15
• pT3 : 40%
• pT4 : 50%

44. Contd…

45. Contd…

46. NEOADJUVANT CHEMOTHERAPY

47. Contd…
 Aim: to reduce micro metastasis and improve survival in MIBC

 Advantage:
 Decrease micrometastatic spread
 Potentially downstaging the tumor
 Disadvantage:
 50% without micrometastasis will be overtreated
 Staging error may lead to overtreatment
 Delay in cystectomy may compromise outcome
 Chemo therapy may have side effects that affect outcome of surgery

48. Contd…
NACT followed by Radical Cystectomy is Category 1
Recommendation for stage II or IIIA Bladder cancer.
 If Cisplatin based NACT cannot be given, NACT is not recommended.
NCCN 2019

49. MVAC +Cystectomy Cystectomy
alone
Median survival 6.2 years 3.8 years
Pathological Complete
response
38% -

52. Contd… (Randomized Phase III Trials of Neoadjuvant Chemotherapy)

53. Adjuvant Chemotherapy
 Data are less clear regarding the role of adjuvant CT.
 NCCN recommends (Category 2A) adjuvant chemo if Neo-adjuvant
chemo was not given
 Indications:
• T3 or more
• Node positive
• Positive Margins
NCCN 2019

54. BLADDER PROTOCOLPRESERVATION

55. Methods of Conservation
Conservative
Surgery
1. Partial
2. Trans Urethral
Resection of Bladder
Tumor (TURBT)
1.Radical External
Beam Radiation
Therapy
2. Interstitial
Brachytherapy
Trimodality
Therapy

56. No trials have till date directly compared
Cystectomy and Bladder-preservation

57.  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
bladder
 If bladder preservation is selected, close surveillance is
How To Approach

58. Partial cystectomy
6% to 19% of patients with primary, muscle-
invading bladder cancer are potential candidates
Local recurrence rates range from 38 to 78%
Careful patient selection
◦ Solitary lesion
◦ Located in a region of the bladder that allows for
complete excision with a 2- cm tumor-free margin
(Bladder dome)
NCCN 2019

59. Transurethral Resection of Bladder
Tumor (TURBT) alone
Clinical complete response rates (assessed
cystoscopically with repeat biopsy 3 weeks after initial
TURBT) for T2 and T3 cancers : 10% to 20%
5 year Overall Survival - 27%
TURBT alone is not sufficient as monotherapy in muscle-
invading

60. Radical External Beam Radiation Therapy
 Historically, EBRT was used as monotherapy
 Factors having significant favourable effect on local control with
Radiotherapy:
• Early clinical stage (T2 and T3a)
• Absence of ureteral obstruction
• Visibly complete TURBT
• Small tumor size (<5 cm) solitary , Papillary / Sessile absence of
coexisting carcinoma in situ
Radiation dose used varied
 from 55 to 65 Gy, with 1.8- 2 Gy per fraction in North America
 from 50 to 55 Gy at 2.5 to 2.75 Gy per fraction in the United Kingdom
NCCN 2019

61. CONTD…
 RT alone is inferior to RT +CT
 In a RCT trial of 360 patients, RT with concurrent mitomycin-
C and 5-FU improved 2 year locoregion disease free survival
54%( RT Alone arm) to 69% ( RT +CT)
 Radiaotherapy alone is indicated only for those patients who
cannot tolerate radical cystectomy or Concurrent
chemoradiotherapy.

62. Interstitial Brachytherapy
 Historic literature on the use of brachytherapy
 Combined with EBRT to provide a radiation boost to the primary tumor
 Indication: Solitary TCC with a diameter of less than 5 cm
 Five-year local control rates for selected patients 70% -90%
• High rates of bladder preservation
 Acute toxicity :
Fistula formation with wound leakage
 Most of these series is the very low patient numbers and long time spans
reported, suggesting that these techniques are only rarely used, even in
centers with the relevant expertise

63. TRIMODALITY THERAPY
RT
TURBT
CHEMO

64. Indications-
 solitary tumors <5cm
 negative nodes
 no carcinoma in-situ
 no tumor related hydronephrosis
 good pre-treatment bladder function.
 T2-T4a stage
CONTD….
NCCN 2019

65. CONTD….
 In the United States, a radical cystectomy remains the
standard treatment.
 For selected patients, a safe and effective alternative to
immediate radical cystectomy
 Successful bladder-preserving approaches have evolved
during the past three decades .
 10% to 30% of the patients will ultimately require a salvage
cystectomy

66. CONTD…
UKUSA
DEVITA 11TH EDITION

67. Results of Multimodality Treatment
for Muscle-Invading Bladder Cancer

69. Trimodality is better then Radical Cystectomy
alone ?

70. MIBC: Survival Outcomes in Contemporary
Series

75. Patterns of Failure
NMIBC muscle-invasive Regional nodal distant failures
5 Year Rates 26% 16% 12% 32%
10 Year Rates 26% 18% 14%, 35%
• The risk of salvage cystectomy at 5 yr and 10 yr was 29% and
31%
• Patients requiring a salvage cystectomy had a higher proportion
of cT3-4a disease (43% vs 30%), and had a significantly higher
rate of initial incomplete TURBT.

82. In truth, surgery and radiotherapy are
not competing, but are complementary
approaches to invasive bladder cancer

83. AFTER ALL ITS…..TEAM EFFORT

85. INDICATIONS-
- In recurrent Ta and T1 (but not Tis)
- Stage T2-T4
- For palliation in metastasis
-Munro et al. studied outcomes in 458 patients with invasive bladder cancer
treated between 1993 and 1996. Overall 10 year survival was similar between
those who underwent radiotherapy(22%) versus radical cystectomy (24%).
Contd….

86. Contd….
Concurrent chemo-radiation as a part of
multimodality bladder sparing protocol in
T2-T4 N0 M0
Neoadjuvant radiotherapy
Adjuvant radiotherapy

87. Preoperative Radiation therapy
AIMS-
 Down staging
 Decrease in incidence of local recurrence
 Improve survival
TRIALS-
 Only of historical significance
 A retrospective study from MD Anderson Cancer Center
assessed pre op RT(50 Gy) vs surgery alone.
 5 yr local control rate was 91% vs 72% respectively (p =
0.003).
 No other trials carried out showed any evidence of
worthwhile benefit.

88. Post-operative Radiotherapy
Limited data from randomized trials
 Indication: pT3-T4, positive surgical margins , pN +
Dose: Areas at risk for harbouring residual
microscopic disease should receive 45 to 50.4 Gy
EBRT.
Involved resection margins and areas of extranodal
extension should be boosted to 54 to 60 Gy.

89.  Opposing anterior and posterior fields used
 35 Gy in 10 Fr over 2 weeks (symptomatic improvement-71%)
Or
 21 Gy in 3 Fr over 1 week (symptomatic improvement- 64%)
PALLIATIVE TREATMENT

90. SIMULATION
 CT Simulation preferred
 Patient Position :supine with arms on chest.
 Immobilization :knee and ankle rest
 Bowel preparation: rectum should be empty of flatus and faeces,
use of daily micro enemas may be considered.
 Bladder preparation: Empty bladder prior to scan.
 (Special bladder protocol can be followed for conformal planning
to account for organ motion)
 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

91. Simulation: need of contrast
 For X Ray based planning:
catheterization f/b introduction of perurethral contrast to
define bladder wall.
 Conventional simulation involves: AP-PA & lateral
radiographS
 For CT based planning
IV contrast used to facilitate nodal delineation
 CT scan performed with 3 to 5-mm slice spacing from
to 3 cm above the dome of the bladder or bottom of L5
(whichever is higher) to bottom of ischial tuberosity

92. Conventional Radiotherapy Volumes
 2 phased treatment
Phase I: Field border
superior border :at the L5-S1 disc space
inferior border: below obturator foramen
Anteriorly: 1.5 to 2 cm from the most anterior aspect of the
bladder
posterior border: about 2.5-3 cm posterior to posterior
aspect of the bladder.
Laterally:1.5-2 cm to the bony pelvis at its widest section
 Dose:40-45 GY @ 1.8-2Gy/#

94. Boost phase
Entire bladder excluding the nodes and then give
a further boost to the tumor alone (3 phase
treatment).
Dose:10-15 Gy to entire bladder and upto 66 Gy to
tumor.
OR
Treat the bladder + tumor with a 2-cm margin to a
total dose of 66 Gy

95. Conformal RT Volumes
Contouring
 Gross Tumor Volume (GTV): macroscopic tumor
GTV_Primary or GTV_LN (Lymph Node)
 Clinical target volume (CTV):- CTV_Primary +CTV_LN
 CTV_Primary: GTV + whole bladder
 In patient with tumors at the bladder base, the proximal urethra(in
both genders), and the prostate and
the prostatic urethra(in males) to be included in the CTV.

96. Contd….
CTV_lymph node (CTV_LN):
External iliac lymph.Internal iliac lymph nodes-, along its branches
(obturator, hypogastric)Presacral
lymph node
Planning target volume (PTV_Primary):
CTV_Primary +1-1.5 isotropic margin
PTV_LN: 1 cm isotropic margin + CTV_LN.

97. Radiation Therapy Doses
 • Optimal radiotherapy schedule is yet to be established
• commonly used schedule :
 SPLIT SCHEDULE
• In U.S split schedules often used are 39 or 40 Gy in 1.8-
or 2-Gy fractions with an interval cystoscopy;
• Patients with responding disease proceed to a total dose
of 64 to 66 Gy.
 SINGLE PHASE TREATMENT
• In the United Kingdom, single radical course, usually to
the whole bladder, only
• Typical dose schedules would be 64 Gy in 32 fractions or
hypo fractionated schedules such as 55 Gy in 20 fractions.

98. 2D vs IMRT vs HELICAL TOMOTHERAPY
 Hsieh et al. compared 19 patients of carcinoma bladder
treated with above 3 techniques.
TOMO THERAPY leads to better conformity & better OAR
sparing

100. Contd….
Recommended dose constraints
are:
Rectum V50 <60 per cent
femoral heads V50 <50 per cent
small bowel V45< 195cm3.

101. TAKE Home Message

102. NMIBC is treated by TURBT followed by Intravesical
therapy
In MIBC, radical cystectomy is the standard
procedure.
Tri-modality therapy is an alternative to radical
cystectomy for patients with muscle-invasive bladder
cancer, and is associated with comparable long-term
term survival and high rates of bladder preservation.
CONTD…..

103. CONTD…..
Newer technologies like IMRT, Helical
tomotherapy, IGRT have added advantage of OAR
sparing.
Cisplatin based multi agent neoadjuvant
chemotherapy has a survival benefit.
Adjuvant RT may be beneficial in selected patients.
In advanced and metastatic disease, platinum
based chemotherapy is the sole treatment.

104. Thank you

105. Bladder protocol
 Patient will be asked to void the urine and empty the bladder as
much as possible.
 Patient will be asked to drink 500 ml of water and time will be
recorded.
 After 60minutes of drinking the water CT simulation without contrast will
be performed suggestive of full bladder.
 Thereafter, patient will be asked to void the urine and empty the bladder
as much as possible and CT Simulation with contrast enhancement will be
performed suggestive of empty bladder
 Both images (with full bladder and empty bladder) will be reviewed for
tumor delineation to ensure that in all possible circumstances the PTV
includes the maximum extension of the full bladder.
 However the CT slices with empty bladder will form the primary image for
GTV and CTV delineations.

106. Radiotherapy
Initial target volume-primary tumor+local extensions+whole
bladder+pelvic lymph nodes including common iliac nodes
(if tumor at bladder base-proximal urethra in women and prostate
and prostatic urethra in men are included)
Patient is treated in supine position and empty bladder.
 Patient treated by 4-6 MV linac or Cobalt-60 teletherapy machine.

107. TWO FIELD TECHNIQUE
FIELDS- AP-PA fields 15 x 15 cm
Antero-posterior fields
 Superior-between L5 and S1
 Inferior-lower border of obturator foramen (if bladder neck and/or
prostatic urethra- 1.5 cm below obturator foramen)
 Lateral-bony pelvis+ 1.5 -2 cm

108. FOUR-FIELD BOX TECHNIQUE-
 Antero-posterior field-
 Superior-between L5 and S1
 Inferior-lower border of obturator foramen (if bladder neck and/or
prostatic urethra- 1.5 cm below obturator foramen)
 Lateral-bony pelvis+ 1.5 -2 cm
 Lateral fields-
 Superior and inferior same as A-P fields
 Anterior-anterior to pubic symphysis+ 1 cm
 Posterior- middle of S2 vertebra

109.  Anterior-posterior field- femur heads are shielded
 Lateral fields-two-thirds of posterior rectum and small intestines
are shielded.
 Boost field-
 Bladder + 1.5-2 cm margin
Initial target volume (whole pelvis)-
44 Gy in 22 Fr over 4.2 weeks
Boost to bladder alone (after whole pelvic irradiation)
20 Gy in 10 Fr over 2 weeks

110. Target volume definition
 CTV defined as the GTV (primary tumour and any extravesical
spread) and the whole bladder.
 In patients with tumours at the bladder base, the proximal urethra
and in men the prostate and prostatic urethra are included on the
CTV.
 The PTV is the CTV with a 1.5–2 cm margin.
Recommended dose constraints are:
 Rectum V50 <60 per cent
 femoral heads V50 <50 per cent
 small bowel V45< 195cm3.

111. CT axial slice with CTV whole bladder, PTV and OAR.
Rectum-yellow, femoral heads-green

112. 3 D conformal Radiotherapy
 CT scans used to accurately determine the location of the
prostate, seminal vesicles, bladder, rectum, and penile bulb.
 3-D treatment plan specifically designed for each individual
patient.
 with10–15MV photon beams
Advantage
higher doses lead to excellent cure rate.
Less dose to critical organs – reduced toxicity
rectal wall dose [<30% of the prescription dose]
bowel dose to 65%

113. Axial CT slice showing conformal plan for whole bladder irradiation

114. SURVIVALAFTER RADIOTHERAPY
T stage 5 yr Survival
T1 35-70%
T2 10-60%
T3 10-40%
T4 0-16%

115.  INDICATIONS-
 Positive margins
 Node positive disease
 T3,T4 disease
 Lymphovascular invasion
 Perineural invasion
 Dose- 50.4 Gy, 2 Gy/ Fr in 5 weeks
Parson and million reviewed results of retrospective studies
and concluded that post-op RT improves outcome by 15-20%
at 5 years

116. SUMMARY
 Gold standard for duagnosis-TURBT
 MRI is the investigation of choice
 Cystoscopy –primary modality of diagnosis
 Low risk groups-BCG maintenance not indicated
 Overall 5 year survival with primary cystectomy and salvage
cystectomy are similar
 Non muscle invasive disease -TUR f/b intravesicle therapy
 For muscle invasive disease maximum TUR /cystectomy /
radiotherapy ± CT for T2-T4a and radiotherapy ± CT for advanced
disease

117. MAXIMAL TURBT + CONCOMITANT CHEMORADIATION
40 Gy in 2 Gy per fraction with 3 weekly cisplatin 100mg IV
Interval cystoscopy
Patient with responding disease NO response Radical
cystectomy
Proceed to total dose of 64 to 66 Gy with 3 weekly cisplatin 100mg IV
CR-47-87%
5 year OS-30-70%

118. interstitial brachytherapy
Indications
 solitary T1-T2 tumours, 50 mm or less in diameter
Contraindications
 Tumour invasion of the bladder neck
 Tumour extending to perivesical fat (T3)
 Multifocal bladder cancer
 Lymph node involvement
 Clinical target volume- the gross disease (or the bladder scar
after partial cystectomy) with margin of 10 mm

119.  Preoperative-
 60 - 65 Gy LDR at 40-80 cGy/hr
 After 40Gy (2 Gy fractions fr) by EBRT a boost dose of 25 - 30
Gy LDR at 40-80cGy/hr
 After partial cystectomy –
 55 - 60 Gy LDR at 40 to 80 cGy/hr over 4-5 days
 21 Gy HDR in 3Gy per fraction with 2 fractions per day 6 hours
apart.

120. s
 LOCAL CONTROLAND SURVIVAL
T1 T2a T2b
5 YEAR
SURVIVAL
70-90% 51-66% 34-70%
10 YEAR
SURVIVAL
72-78% 34-37% -
LOCAL
CONTROL
91% 84% 72%

121. TARGETED THERAPY
 ATEZOLIZUMAB (TECENTRIQ)
 approved -May 18th, 2016
 Class-PD-1/PD-L1 inhibitors
 approved for locally advanced or metastatic urothelial carcinoma whose
disease has worsened during or following platinum-containing chemotherapy,
or within 12 months of receiving platinum-containing chemotherapy, either
before (neoadjuvant) or after (adjuvant) surgical treatment.
 1200 mg administered as an intravenous infusion over 60 minutes every 3
weeks until the cancer progresses or side effects become intolerable
 “Positive” for PD-L1 expression-26 % tumor response
 “Negative” for PD-L1 expression-9.5% tumor response
 $12,500 per month

122. DURVALUMAB (IMFINZI)
 Approved -February 2016
 PD-L1 inhibitor
 locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or who have disease progression within 12 months
of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.
 10 mg/kg administered as an intravenous infusion over 60 minutes
every 2 weeks until disease progression or unacceptable toxicity.
 PD-L1 expression -ORR was 26.3%
 No PD-L1 expression-ORR was 4.1%

123. cTa low grade
Observation or
intravesical
chemotherapy
cTa high grade
Incomplete
resection
TURBT
BCG (preferred)
Or intravesical
chemotherapy
Or observation
No mucle in
specimen
TURBT
BCG (preferred)
Or intravesical
chemotherapy
or observation

124. cT1 low grade
TURBT
RESIDUAL DISEASE
BCG /
Cystectomy
NO RESIDUAL
DIASEASE
BCG/
intravesical
chemothera
-py/
observation
cT1 high grade
TURBT
RESIDUAL
DISEASE
BCG /
cystectomy
NO
RESIDUAL
DIASEASE
BCG/
intra-
vesical
chemother
apy/
observatio
n
C
Y
S
T
E
C
T
O
M
Y

125. Any Tis
BCG

126. cT2 node negative
Neoadjuvant
cisplatin –based
combination
chemotherapy
followed by
radical
cystectomy
Based on
pathologic risk
(pT3-4 or
positive
nodes),
consider
adjuvant
chemotherapy
if no
neoadjuvant
treatment
given
Partial cystectomy
and neoadjuvant
cisplatin-based
combination
chemotherapy
Based on
pathologic risk
(pT3-4,
positive nodes,
positive
margin, high-
grade),
consider
adjuvant RT or
if no
neoadjuvant
treatment
given,
chemotherapy
Bladder
preservation
following maximal
TURBT with
concurrent
chemotherapy
Reassess tumor
status after 3
weeks after 40-45
Gy OR 2-3
months after full
dose (60-65 Gy)
No tumor
Completion
of definitve
RT or
Observatio
n
tumor
cystecto
my
Non-cystectomy
patients-concurrent
chemoradiotherapy or
RT or TURBT alone
Reassess tumor status
after 2-3 months after
treatment
No
tumor
observ
ation
tumor
CT or
concurrent
chemoradio
therapy (if
no prior
RT) or
palliative
TURBT
and best
supportive
care)

127. cT3,cT4a node negative
Neoadjuvant
cisplatin-based
combination
chemotherapy
followed by
radical
cystectomy
Based on
pathologic risk
(Pt3-4 or
positive nodes),
consider
adjuvant
chemotherapy if
no neoadjuvant
treatment taken
Bladder preservation following
maximal TURBT with concurrent
chemotherapy
Reassess tumor status 3 weeks after
40-45 Gy OR 2-3 months after full
dose (60-65 Gy)
no tumor
Completion of
definitive RT or
observation
tumor
cystectomy
Non-cystectomy candidates-
concurrent chemoradiotherapy or
RT or TURBT alone
Reassess tumor status 2-3 months
after treatment
No tumor
observation
tumor
CT/concurrent
chemoradiothe
rapy (if no
prior RT) or
palliative
TURBT and
best supportive
care

128. cT4b node negative
Negative nodes on biopsy or CT or MRI
Chemotherapy
After 2-3 cycles,reassess with
cystoscopy, EUA, TURBT, and imaging
of abdomen/pelvis
No tumor
Cosolidation
chemotherapy or
chemoradiotherap
y (if no previous
RT) or completion
of RT or
cystectomy
tumor
Systemic therapy
or
chemoradiotherap
y (if no previous
RT) or change in
CT or cystectomy
Concurrent chemoradiotherapy
Reassess tumor status 3 weeks after 40-
45 Gy OR 2-3 months after full dose
(60-65 Gy)
No tumor
Consolidation
chemotherapyor
chemoradiatherap
y (if no previous
RT) or completion
of RT or
cystectomy
tumor
Systemic therapy
or
chemoradiotherap
y (if no previous
RT) or completion
of RT or
cystectomy

129. cT2, cT3, cT4a, cT4b node positive (on biopsy or CT or MRI)
Chemotherapy or concurrent chemoradiotherapy
Evaluate with cystoscopy, EUA, TURBT, and imaging of abdomen/
pelvis
No tumor
Boost with RT or cystectomy
Tumor present
Treat as recurrent or persistent
disease

133. ARTERIAL
SUPPLY
VENOUS
DRAINAGE
LYMPHATIC
DRAINAG
NERVE
SUPPLY
Superior vesical
artery
Vesical venous
plexus
External iliac
nodes (main)
Vesical plexus of
nerves (derived
from inferior
hypogastric plexus)
Males-Inferior
vesical artery
Drains into Internal
iliac veins
Internal iliac nodes
Female-uterine
and vaginal artery
instead of inferior
vesical artery
Aortic nodes
Obturator artery
Inferior gluteal
artery

134. Target volume definition
 GTV is the primary bladder tumour, defined on MRI/CT fusion
 CTV defined as the GTV (primary tumour and any extravesical spread) and the
whole bladder. In patients with tumours at the bladder base, the proximal urethra
and in men the prostate and prostatic urethra are included on the CTV.
 The PTV is the CTV with a 1.5–2 cm margin. OAR should be outlined including
rectum, femoral heads and small bowel.
 Recommended dose constraints are: rectum V50 60 per cent, V60 50 per cent;
femoral heads V50 50 per cent; small bowel V45 250 cm3.
 For palliation of T4 tumours and pelvic nodal disease, the PTV must encompass
the primary disease and its extension into the pelvis

136.  Narrow Band Imaging-two narrow bands of light are
absorbed by hemoglobin
 415 nm-analysis of mucosa
 540 nm-analysis of deeper submucosal blood vessels.
 no need of contrast
 high false positives.

138. Axial high-resolution T2-
weighted MR image
shows multifocal bladder
tumors (black
arrowheads)
STAGE Ta
Coronal T2-weighted MR
image shows an irregular
hypointense mass (*)
along the bladder
dome,perivesical
extension (arrows)
STAGE IIb

139. Axial high-resolution
T2-weighted MR image
shows a bladder tumor.
Arrow = extravesical
mass , arrowhead =
normal detrusor muscle.
STAGE III B

140.  Repeat TURBT- indications
 Incomplete initial resection
 No muscle in original specimen for high grade
 Any T1 lesion
 Large or multifocal lesions
 Adequate staging not possible with first TURBT
 Incomplete resection and considering tri-modality bladder
preservation therapy. (maximal TURBT done)
Contd….

141.  Flexible cystoscopy- pretreatment planning and biopsy of lesion to assess pathology,
grade, and depth of invasion
-White light cystoscopy (WLC)-papillary tumors
-Blue-light cystoscopy- detects more Ta tumors and CIS lesions, high false-positives esp. in
case of recent TURBT and BCG therapy.
Flexible cystoscopy with urine
Cytology- STANDARD OF
BLADDER SURVEILLANCE

142. Immediate post-operative intravesical chemotherapy-
- Both muscle invasive and non muscle invasive tumors
- For one hour
- Within 24 hours after initial TURBT
- Mitomycin-C used most commonly (40 mg)
- Not given if-extensive TURBT
-suspected bladder perforation
reduce relative risk of recurrence by 24.2%
no impact on disease progression and disease survival

143. interavesical treatment
Induction (adjuvant) intravesical chemotherapy or BCG-
- Non-muscle invasive bladder carcinoma
- BCG, mitomycin-C, gemcitabine
- 3-4 weeks after TURBT
- weekly instillation for 6 weeks
- maximum 2 consecutive cycles inductions without complete response
BCG reduces mortality by 23%

144. interavesical treatment
Maintenance intravesical BCG-
 For CIS, intermediate and high risk tumors
 SWOG regimen- 6 week induction course of BCG followed by
maintenance with two cycles of BCG instillations three weeks apart (on
day 0 and 21) at months 3, 6, 12, 18, 24, 30, and 36.
 Intermediate risk NMIBC- given for 1 year
 High risk NMIBC-given for 3 years
With BCG maintenance, 32% reduction in risk of recurrence for BCG as
compared to mitomycin-C.
Without BCG maintenance, 28% increase in risk of recurrence with BCG

145.  MODALITIES
 CHEMOTHERAPY-
 neoadjuvant chemotherapy
 concomitant chemoradiation in bladder preservation
 adjuvant chemotherapy
 SURGERY-
 partial cystectomy
 radical cystectomy
 RADIATION THERAPY-
 pre-op radiation therapy
 concomitant chemoradiation in bladder preservation
 post-op radiation therapy

146. SYSTEMIC THERAPY
Peri-operative chemotherapy (neoadjuvant or adjuvant)
Neoadjuvant chemotherapy is given in stage T2-T4a
Standard regimens-
DDMVAC (dose-dense methotrexate, vinblastin, doxorubicin, and
cisplatin) with growth factor x 3-4 cycles
Gemcitabine and cisplatin x 4 cycles
CMV (cisplatin, methotrexate, and vinblastin) x 3 cycles

147. REGIMENS DOSAGE
GEMCITABINE /
CISPLATIN
GEMCITABINE 1000mg/m 2 on days 1,8
,15 of a 28 day cycle or
day 1,8 of a 21 day cycle
CISPLATIN 70 mg/m2 on day2
Dose Dense MVAC METHOTREXATE 30 mg/m2 on day 1 or
2 of a 14 day cycle
VINBLASTINE 3 mg/m2 on day 1 or day
2
DOXORUBICIN 30 mg/m2 on day 1 or
day 2
CISPLATIN 70 mg/m2 on day1
CMV METHOTREXATE 30 mg/m2 on day 1 ,8 of
a 21 day cycle
VINBLASTINE 4 mg/m2 on day 1, 8
CISPLATIN 100 mg/m2 on day 2
before hydration
Folinic acid 15 mg every 6 hours on
day 2 , 9 after hydration

148. NEOADJUVANT CHEMOTHERAPY-
5 year OS- improved by 5%
5 year DFS- improved by 9%
survival benefit of 31 months (77 months vs 46 months)
reduced rate of residual disease (15 % vs 40%)
ADJUVANT CHEMOTHERAPY-
META-ANALYSIS shows a 25% relative reduction in risk of
death.

149. partial cystectomy
cT2 muscle invasive disease with solitary lesion in dome of bladder
with a margin of 2cm
 Bilateral pelvic lymphadenectomy including common iliac, internal
iliac, external iliac and obturator nodes.
 C/I in carcinoma in-situ, involvement of bladder neck and trigone
 5-year OS- 25-60% , over all recurrence rate-40-78%

150. radical cystectomy
RATIONALE-
 Good long term survival rates
 Lowest local recurrence
 Improved morbidity and mortality
 accurate pathologic staging of tumor and regional lymph nodes
 STANDARD FORM OF THERAPY FOR HIGH GRADE,
INVASIVE BLADDER CARCINOMA

151.  en bloc removal of the
-pelvic lymph nodes
-pelvic organs anterior to the rectum–bladder, urachus, and
visceral peritoneum
-prostate and seminal vesicles in men
-ovaries, fallopian tubes, uterus, cervix and vaginal cuff in
women.

152. radical cystectomy
INDICATIONS-
 Residual high-grade cT1, cT2, cT3 and cT4a disease
 Poor bladder function
 Diffuse bladder involvement
 Multiple tumours
 Extensive carcinoma in situ
 Hydronephrosis- C/I to radiotherapy
 Large tumours 5 cm with extravesical mass
 SCC and adenocarcinoma
 Done within 3 months after TURBT, delay more than 3 months undermine survival

153. STAGE No. of patients OS -5 YEAR OS-10 YEAR
T2aN0 94 77 57
T2bN0 98 64 44
T3N0 135 49 29
T4aN0 79 44 23
EXTRAVESICAL
N0
214 47 27
All node negative
pooled
808 69 49
All node positive
pooled
246 31 23

154. Reconstruction
Types of urinary diversion post-cystectomy-
 Continent diversion- continent cutaneous reservoirs
- orthotropic neobladders (done most
commonly)
 Incontinent diversions- ileal conduit
- uretero-sigmoidostomy

156. THREE-FIELD TECHNIQUE-
 Field
1 anterior - 15x14 cm
2 lateral - 15x12cm with 450 wedges

157. THREE-FIELD TECHNIQUE-
 An anterior and two posterior oblique wedge fields with an angle
of 110 degree between two posterior oblique wedge fields, to
spare rectum.

159. intravesical chemotherapy
Most commonly used agents
 Mitomycin c
40 mg weekly x 6 cycles
 Doxorubicin
60 mg in 50 ml normal saline for 60 minutes x 8cycles
 Thiotepa
60mg in 60ml sterile water weekly x 4 -6cycles