Urinary bladder collects urine from the kidney which is then passed through the urethra. Cancer is abnormal growth of cells leading to tumour in urinary bladder. Bladder Cancer is diagnosed with cystoscopy and biopsy . Treatment of Bladder cancer is done as per stage. It includes Radical Cystectomy, Plevic Lymphadenectomy, Ileal conduit, Neobladder as surgical options.

1. BLADDER CANCER
MUSCLE INVASIVE &
METASTATIC
DR SWATI SHAH
PELVIC ( URO & GYNEC) AND ROBOTIC ONCOSURGEON
MS, DNB

2. INTRODUCTION

3. MIBC
• 30% of Ca Bladder
• 80% denovo
• 15- 20% progress from NMIBC
• T2+
• Muscle invasive (Not Lamina Propria invasive)
• Higher incidence of lymphatic spread and metastasis

4. MUSCLE-INVASIVE BLADDER
CANCER (T2, T3, T4)
CIS
Ta
T1
T2
T3

7. INCIDENCE OF LN DISEASE -
STAGEWISE
• T1 – 5 %
• T2 – 15-25%
• T3 – 35-50%
• T4 – 40-50%

8. PRELIMINARIES.....

9. INVESTIGATION
• TUR biopsy
• If T1 – Check re-resection
• Bimanual examination –
• under anesthesia, before & after TUR
• Complete physical examination and blood
investigations
• Imaging 1952, Marshal
T2a –nonpalpable
T2b – induration but no palpable 3
dimensional mass
T3 - palpable 3 dimensional mass
T4a – adjacent organ involvement
T4b – fixed to pelvic wall

10. INVESTIGATION
• CECT –
• Growth characteristics
• Nodal status
• Adjacent invasion
• Upper tract
• Metastasis
• MRI
• T2 differentiation
• Pelvic organ involvement
• LN
• CXR / CT
• Bone scan
• PET
• Liver function test

11. PROGNOSTIC FACTORS

12. PROGNOSTIC FACTORS
• Tumour stage & LN status - independent prognostic
factors for DFS & OS
• Among node +ve patients
• OC disease better survival than EV
Stein 2003, Herr 2002, Mills 2001, Vieweg 1999
• Substratification of nodal status imp for
prognostication

13. PROSTATIC INVOLVEMENT
• Secondary involvement of prostate by TCC
• Prostatic urethra(5%)
• Duct(18%)
• Stroma (64%)
• Imp to plan diversion

14. PROGNOSTIC FACTORS
• KPS < 80 & presence of visceral metastasis
• Median survival 33, 13.4, 9.3 months
• Haemoglobin, serum albumin, KPS, and visceral
metastasis

15. MOLECULAR MARKERS
Peripheral blood
• CEA, CA19-9, CA125, TGFβ, IGF-1, IL-6, E-cadherin,
UPA
Tissue markers
• p53, Rb, E-cadherin, Ki67, VEGF, thrombospondin

16. NOMOGRAMS

17. NOMOGRAMS...
• Nomogram to predict survival following RC have been
develop but cannot be recommended

18. KARAKIEWICZ NOMOGRAM

20. MIBC TREATMENT

21. OPTIONS…..
• Radical Cystectomy
• Surgery + Adjuvant Chemotherapy
• NACT + Surgery
• Pre-op Radiotherapy + Surgery????
Bladder conservation
• Radical Radiation Therapy
• Combined Chemo + Radiation therapy in selected patients
• Partial Cystectomy

22. RADICAL CYSTECTOMY

23. EVOLUTION…..
• More than removing just the bladder (simple
cystectomy)
• First performed in 1800s for bladder cancer
• 1948, landmark report showed a 47% incidence of
local recurrence within 1 year and 33% mortality after
recurrent disease within 1-2 years
• Overall outcomes of patients undergoing simple
cystectomies were poor.

24. RADICAL CYSTECTOMY
• Male, Female
• Gold standard
• Goal – Complete eradication of locoregional disease
• Prostate
• Urethra
• Distal Ureters
• Choice of diversion
• Anterior exenteration in female?

25. MODERN RADICAL CYSTECTOMY
• Radical Cystectomy
• Removal of bladder with surrounding fat
• Prostate/seminal vesicles (males)
• Uterus/fallopian tubes/ovaries/cervix (females)
• + Urethrectomy
• Pelvic Lymphadenectomy
• More is better
• Urinary Diversion
• Ileal conduit
• Continent cutaneous reservoir
• Orthotopic neobladder

26. ADVANTAGES AND CONCERNS…
• Treatment of choice : Gold Standard
• Local control 90-95%
• Survival 30-60%
• 50% die of metastatic disease : Related to nodal mets &
depth of invasion : Need for adjuvant / neoadjuvant
therapy
• Operative mortality low – 3%
• Nerve sparing technique preserves potency
• Requires urinary diversion in majority

27. INDICATIONS
• Muscle invasive or locally advanced disease T2-T4a
N0-Nx, M0
• BCG-resistant Cis, T1G3
• High risk recurrent superficial tumors
• Extensive papillary tumors not controlled by TUR

28. STANDARD RC...
• Male:
• Prostate + bladder + macroscopic visible & resectable tumor
extension, adjacent distal ureter + LN
• Female:
• Anterior pelvic exenteration
• include bladder, entire urethra, upper 1/3 vagina , uterus, distal
ureters and LN

29. RADICAL CYSTECTOMY MADE
RIDICULOUSLY SIMPLE: 8 EASY
STEPS

30. Step 1: mobilize the urachus from the umbilicus

31. Step 2: mobilize the bladder from the bowel

32. Step 3: isolate and transect ureters

33. Step 4: complete lymph node dissection

34. Step 5: separate bladder from sigmoid colon

35. Step 6: complete posterior dissection and cut off bladder blood supply

36. Step 7: complete anterior dissection and isolate urethra

37. Step 8: transect urethra and remove specimen

38. HOW TO PERFORM RADICAL
CYSTECTOMY IN MALE?
1. Fr 18 Foley
2. Midline incision
3. Develop space of Retzius
4. Mobilize bladder from pelvic side
wall
5. Divide the urachus remnant
6. Divide vas
7. Divide posterior peritoneum to
expose ureters
8. Mobilize ureter proximally to
preserve the periureteral blood
supply
9. Pelvic lymphadenectomy
10. Divide endopelvic fascia
11. Divide lateral vascular bladder
pedicles
12. Establish plane between rectum
and posterior bladder wall
13. Ligate dorsal vein
14. Dissect neurovascular bundles off
prostate bilaterally
15. Incise urethra
16. Divide posterior bladder pedicle

39. HOW TO PERFORM RADICAL
CYSTECTOMY IN FEMALE (ANTERIOR
PELVIC EXENTERATION)?
1. Mobilization of bladder from pelvic side wall
2. Divide urachus
3. Ligate infundibulopelvic ligaments (ovarian artery) and round ligaments
(vas)
4. Incise broad ligament to expose ureters and moblize
5. Pelvic lymphadenectomy
6. Circumferencially incise on cervix
7. Close vaginal defect
8. Dissection of place bt anterior vaginal wall and posterior surface of bladder
9. Divide urethra

40. COMPLICATIONS
• Re-operation (10%)
• Bleeding (10%)
• Sepsis and wound infection (10%)
• Intestinal obstruction or prolong ileus (10%)
• Cardio-pulmonary morbidity
• Rectal injury (4%)
• Cx of urinary diversion
• Peri-operative mortality : 3%
• Early complications (within 3 months of surgery) in 28%
Stein JP, Skinner DG. Radical cystectomy for invasive bladder cancer: long-term results of a standard
procedure. World J Urol 2006

41. RESULTS…
• Pathological upstaging (40%)
• LN metastasis : T1 (10%) , T3-4 (33%)
• Survival
• 10 years RFS: 60%, OS 50% (Stein series)
• 5 years recurrence free survival (Studer series): overall 70%
• 90% in pT1/CIS
• 74% in pT2,
• 52% in pT3, and
• 36% in pT4
• 5 yr OS: 60%
• Long term survival in LN +ve: 20% - 30%

42. RADICAL CYSTECTOMY
OUTCOMES
• 35-40% will develop
a recurrence after
surgery
• Most recur within
first 3 yrs after surgery
• Usually at a distant
site
• Almost all will
eventually die from
their disease
Stein JP, et al. J Clin Oncol 19:666, 2001

43. RADICAL CYSTECTOMY
OUTCOMES
• 35-40% will develop
a recurrence after
surgery
• Most recur within
first 3 yrs after surgery
• Usually at a distant
site
• Almost all will
eventually die from
their disease
Stein JP, et al. J Clin Oncol 19:666, 2001

44. NON-INVASIVE STAGING ALTERNATIVES
IDENTIFICATION & LOCALISATION OF
NODES
• Occult mets in grossly normal nodes common (approx 40%)
• Despite modern imaging, incidence of occult mets 14-27%
(25%)
• CT /MRI fail to predict occult LN mets in 21-15%
• PET scan: False –ve: 33%
• Sentinel LN biopsy: Low accuracy, NOT A STANDARD
PRACTICE!!!
• Surgical excision with HPE - only reliable method of staging
bladder cancer

45. 5 YEAR SURVIVAL
T1,2 50-60%
T3,4 26-44%
N2,3 13-29%

46. IS RADICAL CYSTECTOMY
WORTH FOR T3B, T4A
• Morbidity 5-30%
• Mortality <5%
• Meta analysis – Significant recurrence free survival and
good symptom relief
• Emphasis on meticulous clearance of pelvis and
extended lymphadenectomy

47. LYMPHADENECTOMY

48. IMPACT OF LND
• Valuable staging manouevre
• Identifies high risk group requiring adjuvant therapy
• Prognostication
• Therapeutic in presence of micromets
Curative potential & survival benefit (Stein 2003, Skinner 1982, Madersbacher 2003, /vieweg
1999)
• Optimal boundaries need to be defined to accurately diagnose
mets & to improve therapeutic benefit without increasing
morbidity

49. IMPACT OF SURGICAL
TECHNIQUE ON OUTCOMES
• More extended lymph nodes dissection = better
outcomes
• More lymph nodes removed = better outcomes
• Lower positive margin rate = better outcomes
• More experienced surgeons = better outcomes

50. NEW INSIGHTS INTO LN
DRAINAGE - 2003
• 290 patients RC+ Extended LND
• LN +ve 27.9%
• 15.8% located lat to ext iliac vessels
• Isolated LN involvement in presacral or common iliac
regions in 25%
• Among pelvic LN +ve, 57% also had +ve nodes in
common iliac & 31% above aortic bifurcation
With standard LND
74.1% +ve nodes would have been left behind
6.8% mis-classified as LN -ve
Leissner 2003

51. WHICH ASPECTS OF LND
CONTRIBUTE TO IMPROVED
RESULTS?
• No of lymph nodes dissected, independent of no of +ve
nodes
• Extent of dissection: Standard vs Extended (Paulson 1998)
• Node -ve: Extended 90% vs 71% Standard
• Benefit regardless of the T stage (OC 85% vs 64%)
• Node +ve: 24% vs 7%
• Herr (2003): RCT
• No LND (33%)
• vs Obturator (46%)
• vs Standard (60%)

52. NUMBER OF NODES SAMPLED AFFECTS
SURVIVAL IN BOTH NODE NEGATIVE AND NODE
POSITIVE PATIENTS
Node negative Node Positive
Herr Urology 61:105, 2003

54. Standard LND Extended LND
PELVIC LYMPHADENECTOMY

55. STD VS. EXTENDED
STANDARD PLND
• Proximal: Bifurcation of common iliac
artery
• Lateral :Gentitofemoral nerve
• Medial: Bladder wall
• Distal: Circumflex iliac vein
• Pelvic floor and hypogastric vessel
Anything less = limited
Anything more = extended
EXTENDED PLND
In the boundaries of:
• Aortic bifurcation and common iliac
vessel
• Genitofemoral nerve
• Circumflex iliac vein and node of
Cloquet
• Hypogastic vessels
Including:
• obturator, internal, external, common
iliac and presacral nodes as well as
nodes at the aortic bifurcation May
also Extend to IMA

56. RATIONALE OF EXTENDED
LYMPHADENECTOMY
• Early lymph node metastasis can occur in pT1 (5%) and
pT2 (18-27%) diseases
• Long term survival is possible in patients with lymph
node metastasis
• 20-30% of metastatic lymph nodes outside the field of
“standard” LND

57. Bladder
Cancer-specific
Survival
Probability
Years after Radical Cystectomy
100
90
80
70
60
50
40
18
30
20
16
14
8
3 yr. ± SE 7 yr. ± SE 10 yr. ± SE
No. LN removed ≥12 78.1 ±1.9% 71.8 ±2.4% 63.6 ±3.6%
No. LN removed <12 59.2 ±5.1% 44.9 ±6.3% 44.9 ±6.3%
10
0
4 6 10 12
No. lymph node removed ≥12
n=613
No. lymph node removed <12
n=113
Log rank test
P<0.0001
All Patients

58. RC IN NODE POSITIVE?
• Nodal involvement most important prognostic factor
Three scenarios
• Node involvement highly suspected on imaging
• Nodal involvement highly suspected ‘on table’
• Gross nodes on imaging or intra operative

59. RC IN NODE POSITIVE
• 24% survival at 10 years with cystectomy alone.
• High volume centres
• Most response seen in pT0-pT2
• Extended lymphadenectomy with chemo – cure rate of
around 40%
• Nodes above IMA – Systemic chemotherapy

60. WHEN CYSTECTOMY NOT DONE
• Lymph nodes unresectable because of bulky nodes or
gross nodes above iliac vessels
• Extensive periureteral disease
• Bladder fixed to pelvic side wall
• Tumour invading rectosigmoid

61. HIGH RISK FACTORS AFTER
CYSTECTOMY
• Deep muscle invasion or extravesical spread
• Prostate or adjacent organ involvement
• High grade or undifferentiated histology
• Lymphatic or vascular emboli
• Lymph node metastases
• +ve surgical cut margins (Residual)

62. OPEN VS MINIMALLY
INVASIVE APPROACHES

63. Robotic
Radical
Cystectomy
Da Vinci

64. ROBOTIC AND LAP. RADICAL
CYSTOPROSTATECTOMY
• Evolving....
• Morbidity - limited
• Operative time - comparable
• Long-term oncologic outcomes – awaited
• Most authors have favoured an extracorporeal approach based
on currently available technology and using intestinal segments
for the urinary diversion

65. OPEN VERSUS LAPAROSCOPIC
• Technically demanding in laparoscopic procedure
• Urinary diversion is usually performed extracorporeally
• No difference in term of lymph node yield and
complication rate
• Increased operation time but blood loss reduced
• No consensus on oncology outcome

66. OT SETUP

67. PATIENT POSITIONING

68. STD PORT PLACEMENT

69. DISSECTION OF THE URETER...
A, Pelvic sidewall and external iliac artery. B, Hypogastric artery. C, Ureter, retracted
anteriorly by left robotic arm.
D, Bladder and ureteral hiatus. E, Rectum. F, Sigmoid colon. G, Right robotic arm. H,
Suction-irrigator

70. DEVELOPMENT OF THE ANTERIOR
PEDICLE
A, Pelvic side wall; B, obturator nerve; C, internal iliac (hypogastric) artery; D, obturator
artery; E, superior vesicle artery; F, branch off of superior vesicle artery; G, bladder; H,
ureter; I, rectum; J, posterior pedicle to bladder

71. SEPARATING BLADDER AND
RECTUM IN MIDLINE
A, Bladder. B, Rectum. C, Left posterior
pedicle. D, Right robotic arm with
monopolar scissors.

72. DEVELOPMENT OF PLANE
BETWEEN BLADDER AND RECTUM
REVEALS THE POSTERIOR PEDICLE
A, External iliac vein. B, Obturator vein. C, Bladder. D, Rectum. E, Sigmoid colon. F,
Posterior pedicle. G, Superior vesicle artery, cut. H, Branch of superior vesicle artery,
cut. I, Suction-irrigator

73. ENDOPELVIC FASCIA IS SHARPLY
INCISED
A, Pubic bone. B, Pectineal line. C, Bladder. D, Posterior
pedicle, cut. E, Beginning of prostate pedicle. F, Endopelvic
fascia. G, Right robotic arm

74. DROPPING THE BLADDER FROM
ANTERIOR ABDOMINAL WALL
A, Anterior abdominal wall. B, Urachus. C,
Medial umbilical ligaments. D, Bladder. E,
Right robotic arm

75. DVC
A, Pubic bone. B, Puboprostatic ligaments. C, Prostate. D, Bladder.
E, Left robotic arm

76. EXTENDED PLND
A, Posterior peritoneum, cut. B, Common iliac artery. C, External iliac artery. D,
Hypogastric artery. E, External iliac lymph node packet. F, Hypogastric lymph node
packet. G, Presacral lymph node packet. H, Suction-irrigator.

77. TRANSPOSITION OF THE LEFT
URETER UNDER SIGMOID COLON
A, Sigmoid colon. B, Left ureter, passed posterior to the sigmoid mesentery and delivered
to the patient’s right side. C, Hem-o-Lok clip with 0-Vicryl tie attached to the cut end of
the left ureter. D, Right robotic arm.

78. • Followed by neobladder or conduit.....

79. CHEMOTHERAPY

80. HIGH RISK FACTORS AFTER
CYSTECTOMY
• Deep muscle invasion or extravesical spread
• Prostate or adjacent organ involvement
• High grade or undiff histology
• Lymphatic or vascular emboli
• Lymph node metastases
• +ve surgical cut margins (Residual)
Adjuvant therapy indicated

81. PERI-OPERATIVE
CHEMOTHERAPY
RATIONALE
• Deaths from TCC are generally not local events
• Patients die as a result of metastatic disease
• Local interventions will not deal with micro-metastatic
disease
• Systemic therapy must be given to eradicate
micrometastatic disease in order to improve cure rates

82. DRUGS
• Cisplatin alone
• CISCA
• M-VAC
• M-VEC
• GC

83. CHEMOTHERAPY FOR BLADDER
CANCER
• Bladder cancer is a chemosensitive disease
• Active single agents.
RR
• Cisplatin- 70mg/m2 30%
• Carboplatin 20%
• Gemcitabine- 1000mg/m2 20-30%
• Ifosfamide 20%

84. CHEMOTHERAPY FOR BLADDER
CANCER
Combination chemotherapy.
RR
CR
• MVAC 40-75% <20%
• Gem / Cisplatin 40-70% 5-15%
• Gem / Carboplatin 65% 5%
• Taxol / Carboplatin 20-40%
• Metho- 30mg/m2,vinblastin- 3mg/m2, dox-30mg/m2

85. ADJUVANT CHEMOTHERAPY
• In high risk patients to delay recurrence and prolong
survival
• pT3-pT4, N+, M0

86. ADVANTAGES
• Use in high risk patients based on accurate
pathological staging
• Surgery not delayed
• Availability of tissue for analysis of molecular
predictive and prognostic markers
• If micrometastasis present, they can be treated with
chemo with lower tumour burden

87. DISADVANTAGES
• Bladder not preserved
• Delay in starting chemo in occult systemic disease
• Response cannot be easily evaluated
• Surgical morbidity

88. RESULTS

89. RESULTS
• Stockle et al 1995
• M-VAC or M-VEC
• PFS – 13%
• OS – 17.4% vs. 26.9%
• DSS – 17.4% vs. 41.7%

90. ADJ CHEMOTHERAPY
• No RCT to show significant survival benefit
• Used to delay rec
• No trials for for non urothelial CA

91. NEOADJUVANT CHEMOTHERAPY
• Has been used from T2-T4a
• Intent to treat micrometastatic disease at diagnosis

92. ADVANTAGES
• Therapy better tolerated before surgery
• In vivo drug sensitivity testing
• Downstaging; technically easier surgery

93. DISADVANTAGES
• Discrepancies between clinical and pathological
staging – 30%
• Delay in definitive local therapy
• Possible increase in perioperative morbidity

94. RESULTS

95. RESULTS
• SWOG, 2001
• pT0 at surgery – 85% 5 year survival
• Median survival (pT1,2) – 77 months vs. 46 months
• Median survival (pT3,4) – 65 months vs. 24 months
• Neoadjuvant chemotherapy improves survival in
locally advanced bladder cancer

96. NACT -> RCP VS RC ALONE IN T2-
T4A
• Grossman et al -> randomized MIBC to RCP vs 3# MVAC-
> RCP
• mOS = 46 vs77 m , p =0.06
• pT0 = 38% vs 155
• No inc in mmorbidity / mortality
• Meta analysis -> inc OS = 5%, DFS = 9%
• Phase ii trial -> ddMVAC – safer profile
• Shorter time to Sx, inc pCR
• No gr ¾ renal toxicity/ toxicity related death
• BA 06 -> CMV – 16% dec mortality

97. PATIENT COMORBIDITIES FOR
CHEMOTHERAPY
• Karnofsky performance status <80%
• GFR <60ml/min
• Serum creatinine >2mg%
• Ejection fraction <45%

98. RADIATION

99. PRE OP RT??

100. PRE-OP RADIATION THERAPY
• Moderate dose 20 Gy / 5 Fr or 40-50 Gy / 20-25 Fr
• Eradication of primary & nodal disease in few patients
after pre-op RT alone
• No survival benefit in randomised trials
• MD Anderson Trial : Reduces pelvic relapses in T3b
patients (28% vs 9%) No survival benefit

101. PREOPERATIVE RADIATION
THERAPY
• SWOG study (1982) – Five year survival 53% vs. 43%;
OR – 0.95
• Improved survival with preoperative RT not proven
• Better response rate reported with bilharzial bladder
cancer in 2 studies

102. EUROPEAN UROLOGY
GUIDELINES

103. POST OPERATIVE RADIATION
• With availability of efficacious chemotherapy, post op
RT not useful
• Adds more complications

104. NCCN 2015

105. SURVIVAL

107. FOLLOW UP

108. MD ANDERSON PROTOCOL
• PT1 disease: annual history, physical examination, chest x-
ray, liver function tests, and alkaline phosphatase levels.
• PT2 disease : same studies, but they should be performed
every 6 months for 3 years, then annually.
• >PT3 disease should be followed similarly to those with
pT2 disease, except surveillance starts at 3 months, with
CT scans at 6, 12, and 24 months.
• All patients with TCC should have upper tract
radiographic studies every 1-2 years.

109. CONCLUSION.....

110. CONCLUSION
• MIBC – systemic disease
• Needs multimodality treatment
• Radical cystectomy – gold standard
• Extended LND – prognostic advantage
• Neoadjuvant chemo – proven survival advantage
• Bladder conservation ….

111. Inoperable

112. Inoperable patients
 T4b, N2+
 Systemic chemotherapy with M-VAC or GC
 Based on response to chemo, further therapy
 Radical cystectomy
 Radiotherapy
 Palliative TURBT
 Alternative chemotherapy
NCCN guidelines

113. Metastatic bladder cancer

114. Management
 Primary systemic combination chemotherapy
 M-VAC or GC
 Initial response 40-70%
 5 year survival only 5-20%
 Renal dysfunction, poor performance status, advanced
age

115. Results

116. Novel agents
 Vinflunine
 Pemetrexed
 Ixabepilone
 Larotaxel
 Nanoparticle albumin bound paclitaxel
 Oxaliplatin

117. Monoclonal antibodies
 Trastuzumab
 Bevacizumab
 Cetuximab

118. Targeted molecular therapy
 Gefitinib
 Lapatinib
 Sorafenib
 Sunitinib
 Axitinib

119. Treatment Protocol

120. T2
 Radical cystectomy
 Consider neoadjuvant or adjuvant (based on
pathological risk factors) chemotherapy
 Bladder preservation can be discussed
 Unfit patients – TURBT alone or with chemo/RT

121. T3
 Radical cystectomy
 Strongly consider neoadjuvant or adjuvant
chemotherapy
 Bladder preservation can be discussed
 Unfit patients – TURBT alone or with chemo/RT

122. T4
 T4a – Cystectomy + chemotherapy
 T4b – Chemotherapy → repeat TURBT/Imaging →
response → consolidation chemo or RT or cystectomy

123. N+
 Chemotherapy
 Repeat imaging → response →
observation/RT/cystectomy

124. M1
 Chemotherapy
 Investigational agents

125. Non urotheliAL CA
 MIXED –treat same as TCC, explain about poor
prognosis
 Pure SCC – no NACT/ Adj CT; t/t with RCP/ RT;
chemo may be given for M1
 Pure adeno – same as SCC, partial Cx may be
considered for urachal
 Small cell – NACt -> RT/Sx; chemo as for SCLC
 Sarcoma – t/t as for sarcoma

128. References
 Seth P. Lerner, Cora N. Sternberg; Management of Metastatic and
Invasive Bladder Cancer: Urology- Campbell-Walsh 10th ed, 2012
 NCCN clinical practice guidelines in oncology: Bladder cancer,
Version 2.2012
 Arnulf Stenzl et al; Treatment of Muscle-invasive and Metastatic
Bladder Cancer: Update of the EAU Guidelines; European urology
59(2011)1009–1018
 Khochikar MV. Treatment of locally advanced and metastatic bladder
cancer. Indian J Urol 2008;24:84-94
 Nayyar R, Gupta NP. Role of systemic peri-operative chemotherapy
in management of transitional cell carcinoma of bladder. Indian J
Urol 2011;27:262-8

129. Thank you…