Muscle Invasive Bladder Cancer

1. 1
Muscle invasive tumorMuscle invasive tumor
Edmond

2. 2
Case
• M/64y
• Chronic smoker, HT, DM, IHD
• C/o painless gross haematuria x 1y
• FC: one 5cm sessile growth over right lateral
wall
• IVU: upper tract normal
• TURBT: Muscle involved, G3
• CT + CXR: Extravesical extension, enlarged
pelvic LN, no liver/lung/bone metastasis

3. 3
What are the options ofWhat are the options of
treatmenttreatment ？？
• Radical cystectomy
• Radiotherapy
• Chemotherapy

4. 4
Radical cystectomyRadical cystectomy
• Indication:
– 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
• 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

5. 5
• Complications
– Re-operation (10%)
– Bleeding (10%)
– Sepsis and wound infection (10%)
– Intestinal obstruction or prolong ileus (10%)
– Cradio-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 )
• Result:
– Pathological upstaging (40%)
– LN metastasis : T1 (10%) , T3-4 (33%)
• Survival
– 10 years recurrence free survival: 60%, overall survival 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%
• Nomogram to predict survival following RC have been develop but cannot be
recommended

6. 6
How to perform radicalHow to perform radical
cystectomy in male?cystectomy in male?
• Fr 18 Foley
• Midline incision
• Develop space of Retzius
• Mobilize bladder from pelvic side wall
• Divide the urachus remnant
• Divide vas
• Divide posterior peritoneum to expose ureters
• Mobilize ureter proximally to preserve the periureteral blood supply
• Pelvic lymphadenectomy
• Divide endopelvic fascia
• Divide lateral vascular bladder pedicles
• Establish plane between rectum and posterior bladder wall
• Ligate dorsal vein
• Dissect neurovascular bundles off prostate bilaterally
• Incise urethra
• Divide posterior bladder pedicle

7. 7
How to perform radical cystectomy in female (anterior pelvicHow to perform radical cystectomy in female (anterior pelvic
exenteration)?exenteration)?
• Mobilization of bladder from pelvic side wall
• Divide urachus
• Ligate infundibulopelvic ligaments (ovarian artery) and round
ligaments (vas)
• Incise broad ligament to expose ureters and moblize
• Pelvic lymphadenectomy
• Circumferencially incise on cervix
• Close vaginal defect
• Dissection of place bt anterior vaginal wall and posterior
surface of bladder
• Divide urethra

8. 8
Technique to improve QOLTechnique to improve QOL
Level of preservation:
• Anterior & membranous urethra + external sphincter
– For orthotopic neobladder
• Part of prostate and seminal vesicle
– Fertility , potency and continence
• Autonomic & sensory nerve (NVB)
– soft tissue adjacent to the tips of the seminal vesicles.
• Uterus & part of vagina ;
– Improve antomical support for neobladder & autonomic nerves
Disadv:
– Residual Ca prostate (30%)  10% clinically significant
– Increase oncologica risk  need long term data
Adv:
• Improve potency rate after nerve sparing cystectomy (Walsh J Urol 1996)
– 20y – 29y: 100%, 70y – 79y: 20%
– Overall 48%, depends on age of patient
– vs < 30% in non NS cystectomy
• Allow formation of neobladder and more natural voiding

9. 9
Other technical consideration
• Distal ureteral segment
– Length to be removed not defined
– FZ –ve give overall accuracy of > 98%

10. 10
Is radical cystectomy
contraindicated in pt >80yo?
• Cystectomy is associated with greatest
risk reduction in disease-related and non-
disease related death in patient > 80yo
• Pt older than 80 year of age have increase
post-operative morbidity but not increased
mortality
Hollenbeck Urology 2004

11. 11
What are methods of urinaryWhat are methods of urinary
diversion ?diversion ?
• To skin:
– Ureterocutaneostomy
– Ileal conduit
– Continent cutaneous urinary diversion
• To bowel: Ureterocolic diversion
• To urethra:
– Orthotopic neobladder
• Renal deterioration is not more frequent in
refluxing than non-refluxing ureteric implant

12. 12
How to perform ileal conduit ?How to perform ileal conduit ?
• 15cm segment with major arch, 15cm from ileocecal valve
• Ileoileostomy
• Closure of mesenteric window
• Flush conduit with copious saline
• Ureteroileal anastomosis
– Bricker
– Wallace – lowest complication like stricture and leakage, not recommended
extensive CIS (difficult mx in recurrence + bil obstruction)
– Absorbable suture, spatulation, water-tight mucosa to mucosa apposition over
stent (bilateral separate stent)
• Abdominal stoma (everting, tension free, ant abd fascia not too tight)
• Complications
– Fewer than the other 2 urinary diversion method
– Early: pyelonephritis, uertero-ileal leakage, stenosis
– Late: stoma complications (24%), upper tract changes (30%), urolithiasis
– Higher chance or urethral recurrence than neobladder (

13. 13
Continent cutaneous urinaryContinent cutaneous urinary
diversiondiversion
• Suitable candidate: self care ability, renal (CrCl 60ml/min) and liver
function, colonoscopy
• 4 types of continent mechanism
– Appendiceal tunneling
– Terminal ileum and ileocecal valve
– Intussuscepted nipple valve
– Hydraulic valve, as in Benchekroun nipple
• Common reservoirs
– Indiana pouch, Mainz pouch, double T-pouch
• Contraindication: same as neobladder
– Severe neurological & psychiatric illness
– Limited life expectancy
– Impaired LRFT
– +ve urethral margin or other surgical margin

14. 14
Orthotopic Urinary diversionOrthotopic Urinary diversion
• Assessment: self cath ability, renal function 60ml/min, life expectancy
(<75), no liver failure
• Relative contraindication specific to orthotopic bladder :
– Pre-operative RT
– Complex urethral stricture
– Severe urethral sphincter related incontinence
• Contraindication:
– Severe neurological & psychiatric illness
– Limited life expectancy
– Impaired LRFT
– +ve urethral margin or other surgical margin
• Overall risk of urethral recurrence 10%
• Terminal ileum most often used for bladder substitution
• Long term complications:
– urinary retention
– diurnal/nocturnal incontinence
– ureterointestinal stenosis
– metabolic disorders (hyperCl metabolic acidosis)
– Vit B12 deficiency

15. 15
How to perform Studer pouchHow to perform Studer pouch
• 60cm terminal ileum
• 25cm from ileocecal valve
• Distal 40cm placed in U shape, opened along
antimesenteric border
• Ureters anastomosed end-to side fashion to afferent limb
• Closure of anterior and posterior wall of U-shaped ileum
• Cut a hole in dependent portion of ileum
• Uretheroenteric anastomosis

16. 16
What is partial cystectomy?
• Ideal candidate: only 20%
– solitary lesion at dome allowing 2cm margin
– Tumour in diverticulum
• Need cystoscopy every 3 month for at least 2 years
• T3-4 tumors have the highest risk of developing
metastases (70%) but also have the lowest rate (10-
20%) of successful control of local disease with
bladder preservation
– Many of these patients will be curable with PLND
• 5-year survival from 50% to 70%

17. 17
What is the situation cystectomy
is prefer as opposed to RT?
• CIS (RT does not treat CIS)
• Upper tract obstruction
• Inflammatory bowel disease
• Severe irritative LUTS
• Previous RT
But if significant comorbidity or preserve
sexual function > RT

18. 18
Neoadjuvant chemotherapyNeoadjuvant chemotherapy

19. 19
• Advantage:
– At the earliest time point, when the burden of micrometastatic disease is
expected to be low
– In vivo chemosensitivity is tested
– The tolerability of chemotherapy is expected to be better before than after
cystectomy
– Potentially downstaging the tumor
– Did not affect the percentage of cystectomy performable [Nordic Trail 1+2]
• Disadvantage:
– 50% without micrometastasis will be overtreated
– Staging error may lead to overtreatment
– Delay in cystectomy may compromise outcome
– Chemo therapy may have SE that affect outcome of surgery
– Although overall morbidity is similar ,more anemia & neuropathy
• Regimen: MVAC (SWOG 2003), CMV (EORTC)
o GC less toxic with similar efficacy (Dash et al 2003)
Neo-Adj Chemo

20. 20
• Indication :
– Stage II-III and selected T4bN0 or N1 disease
– Good PS (0-1)
– Adequate renal function
• CMV Q3W for 3 cycles
• Advanced Bladder Cancer (ABC) Meta-analysis. [Lancet 2003]
– Analysis of 11 trial
– Cisplatin-containing chemotherapy :
• 5% (45% > 50%) absolute improvement 5yr overall survival
• 9% improvement in 5yr DFS
• 13% reduction in risk of death
– Combination is better than single agent
– Complete tumor response in 30%
– Update in 2005 [EU 2005]
• Absolute overall survival benefit of 5% (95% CI 1-9%, from 45-50%)
• Significant disease-free survival benefit (HR 0.78, 95% CI 0.71-0.86,
p<0.0001) with 9% improvement in 5 years
• Platinum combination significantly better than platinum single agent
– GC: Phase III metastatic trial: similar efficacy with CMV/M-VAC but less toxic
• EAU
– Neoadjuvant cisplatin-containing combination chemotherapy should be considered in muscle
invasive bladder cancer, irrespective of definitive treatment
• Contraindication: PS ≥ 2 and impaired renal function - <50-60 mL/minute

21. 21
What is SPARE trial?
• Cancer research UK
• Randomised trial of muscle invasive tumor
• RT VS cystectomy after neoadjavant
chemotherapy

22. 22
Delay cystectomyDelay cystectomy

23. 23
What is the problem of delay
cystectomy?
• Delay of treatment beyond 90 days of primary
diagnosis caused a significant increase in
extravesical disease (81 vs. 52%), decrease in
overall survival, recurrence-free survival, cause-
specific survival
– Chang SS, et al. Delaying radical cystectomy for muscle invasive bladder
cancer results in worse pathological stage. J Urol 2003;170(4 Pt 1):1085-7.
• Also affect the options of urinary diversion
– Hautmann RE, et al. Does the option of the ileal neobladder stimulate
patient and physician decision toward earlier cystectomy?. J Urol
1998;159(6):1845-50.

24. 24
LymphadenectomyLymphadenectomy

25. 25
Why PLND?Why PLND?
• Chance of LN metChance of LN met
• From Stein series
– Overall estimate ~ 25% patient undergo cystectomy have
LN met
– Superficial disease (P0, Pis, Pa, P1): 5%
– pT2 : 15
– pT3 : 40%
– pT4 : 50%
• EAU - In retrospective studies extended lymphadenectomy
has been reported to improve survival in patients with muscle-
invasive bladder cancer.
• The curative value of lymph node dissection, however, is still
unknown and a standardised lymph node dissection has yet
to be defined
25

26. 26
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
26

27. 27
Extended PLNDExtended 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
• 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
J Stein, D Skinner, 2006 BUJI
27

28. 28
Key Concepts of LN Metastasis
• Number of lymph nodes removed
• Number of lymph node metastasis
• Lymph node density

29. 29
Number of Lymph Nodes
• The number of lymph nodes
assessed pathologically depends,
–Boundaries of the LND
–Pathologist’s diligence in searching
and preparing the lymph nodes
–How the specimen is actually
submitted for pathological evaluation
–Patient’s variation

30. 30
Benefits of Extended LND
• Survival benefit in organ-confined node-
positive bladder cancer patients (TxN+)
-> Some evidence
• Survival benefit in organ-confined node-
negative bladder cancer patients (TxN0)
-> Strong evidence
• Overall 5yRFS
– pT1 76%, pT2 74%, pT3 52%, pT4 36%

31. 31
Benefit of Extended LND
• Patients with TxN+ disease
– Leissner et al. evaluated 79 patients with < 5 positive lymph nodes, and
demonstrated improved survival when >16 lymph nodes were removed,
although a multivariate analysis was not reported. [Leissner, BJU Int
2000]
– Herr et al. reviewed a lymph node-positive cystectomy series of 162
patients and observed that the removal of >13 total lymph nodes was
not a significant predictor of survival on multivariate analysis (P = 0.56).
[Herr, J Urol 2003]
– Stein et al. described the largest lymph node-positive series with 244
patients and observed no recurrence-free survival advantage with the
removal of ≥15 lymph nodes (P = 0.21). [Stein, J Urol 2003]
• However:
– Based on the 1260 patients from SEER database, removal of >10 lymph
nodes was associated with increased overall survival (hazard ratio,
0.52; 95% confidence interval , 0.43 - 0.64). [Wright, Cancer 2009]

32. 32
Leissner, BJUI 2000;85;817-823Leissner, BJUI 2000;85;817-823
5yRFS >=16 <=15
Tis or 1or 2,
pN0
85% 63%
T3 55% 40%
pLN+ 1-5
i.e. density
53% 25%
32

33. 33
Benefits of Extended LND
• In patients with TxN0 disease
– Better and more accurate staging by sampling
more lymph nodes
– Removal of micro-metastasis
– 33% of patients had unexpected microscopic
nodal metastasis to common iliac lymph
nodes
Bochner, J Urol. 2004

34. 34
Survival in patients with N0
disease
Herr, Urol 2003

35. 35
Recommendation
• The Bladder Cancer Collaborative Group
recommends 10-14 lymph nodes should
be removed at time cystectomy
Herr, J Urol 2004

36. 36
Technical Considerations
• Operation technique
– Standardized procedure
– Cystectomy-first or LND-first approach
– Extra operation time (63 minutes)
• Open versus laparoscopic
– Technically demanding in laparoscopic procedure
– No difference in term of lymph node yield and
complication rate
– Increased operation time but blood loss reduced
Finelli, J Urol. 2004. Porpiglia, J Endourol. 2007

37. 37
Why need extended LN?
• 90% of bladder draining LN distal and
caudal to where ureter cross common iliac
arteries [Studer EU2010]
• Limited LND likely understage LN status
[Studer JU2008]
– Cleveland clinic vs University of Bern
– 1) overall pLN +ve rate lower
– 2) more recurrence despite same pT2 / pT3 /
pLN+

38. 38
Where are the regional lymph nodes of the bladder ?
11%
20%
18% 7%
20%
5%
4%4%11%
B. Roth et al., Eur Urol 57:205-211,
2010

39. 39
LIMITED PLND: CC EXTENDED PLND: Bern
Boundaries of Dissection
{median 12 nodes: range 2-31} {median 22 nodes: range 10-43}
Dhar N., Studer U.E. et al., J. Urol 179: 873-878, 2008

40. 40
Patients with pT2 and pT3 N0Patients with pT2 and pT3 N0
bladder cancerbladder cancer
Institution Stage # of Patients # with pN+
CC
Limited
pT2 pN0-2 200 15/200 (7.5%)
Bern
Extended
pT2 pN0-2 150 24/150 (16%)
CC
Limited
pT3 pN0-2 136 29/136 (21%)
Bern
Extended
pT3 pN0-2 172 59/172 (34%)
Dhar N., Studer U.E. et al., J. Urol 179: 873-878, 2008

41. 41
Recurrenc free survival pT2Recurrenc free survival pT2 pNpN0-20-2 & pT3& pT3 pNpN0-20-2
p< 0.001p< 0.001
Limited PLND Extended PLND
0
. 2
. 4
. 6
. 8
1
0 1 2 2 4 3 6 4 8 6 0
C C P a t ie n t s
RFS
M o n t h s
1 9 %
p T 2 a + b , p N 0 - 2 ( n = 2 0 0 )
p T 3 a + b , p N 0 - 2 ( n = 1 3 6 )
p < 0 . 0 0 0 1
6 3 %
0
. 2
. 4
. 6
. 8
1
0 1 2 2 4 3 6 4 8 6 0
C C P a t ie n t s
RFS
M o n t h s
1 9 %
p T 2 a + b , p N 0 - 2 ( n = 2 0 0 )
p T 3 a + b , p N 0 - 2 ( n = 1 3 6 )
p < 0 . 0 0 0 1
6 3 %
B e r n P a t ie n t s
0
. 2
. 4
. 6
. 8
1
0 1 2 2 4 3 6 4 8 6 0
p T 2 a + b , p N 0 - 2 ( n = 1 5 0 )
p T 3 a + b , p N 0 - 2 ( n = 1 7 2 )
RFS
M o n t h s
p < 0 . 0 0 0 1
4 9 %
7 1 %
B e r n P a t ie n t s
0
. 2
. 4
. 6
. 8
1
0 1 2 2 4 3 6 4 8 6 0
p T 2 a + b , p N 0 - 2 ( n = 1 5 0 )
p T 3 a + b , p N 0 - 2 ( n = 1 7 2 )
RFS
M o n t h s
p < 0 . 0 0 0 1
4 9 %
7 1 %
Dhar N., Studer U.E. et al., J. Urol 179: 873-878, 2008

42. 42
limited extended
Overall pLN +ve 13% 26%
LN+ 5y RFS 7% 35%
pT2N0 67% 77%
pT3N0 23% 57%
42

43. 43
Also affect survivalAlso affect survival
• LN density
• Extracapsular extension of LN met
43

44. 44
Can we just perform the PLND only onCan we just perform the PLND only on
the side of tumor?the side of tumor?
• Bilateral nodal involvement is common
even if tumor is limited in the left or right
hemisphere of bladder. Bilateral PLND
should be performed
– Mapping study by Leissner
• In some series, up to 40% of positive
nodes were found in the contralateral side

45. 45
What are the advantages of doing
extended LN dissection?
• Extended PLND increased the total number of LN removed (from
14 to 25) Prospective multicentre study by Leissner
• Extended PLND although takes longer time to perform, it makes
subsequent cystectomy more straightforward because of a better
delineated vascular anatomy
• Cohort data from Bladder cancer collaborative group extended
PLND apparently reduce the incidence of positive surgical margins
• By increase the number of LN removed, it is associated with better
recurrence free survival in patients with organ confined disease,
extravesical disease and patients with nodal disease. (as shown in
multiple series, Stein/Leissner/Herr’s series)
• Although increased operating time, no evidence that extended
PLND would lead to increased morbidity, such as lymphocele, DVT,
bleeding (Stein & Leissner’s series)

46. 46
What are the morbidity and
mortality of PLND?
• According to Stein & Skinner’s series, the
perioperative mortality was 3% with early
complication of 28%. But there were no
perioperative deaths or early
complications related directly to PLND
• Patients who had high dose of irradiation
before operation are at risk of vascular
and associated injury. They are not good
candidates for extended PLND

47. 47
What is the concept of lymph
node density?
• From Stein’s series, LN density was
shown to be an independent significant
prognostic factor
• LN density of <=20%: 40% 10 year
recurrence free survival
• LN density of > 20%: 20% 10 year
recurrence free survival

48. 48
Urethrectomy

49. 49
• What is the urethral recurrence rate after
cystectomy?
– Overall incidence of urethral recurrence in retained
male urethra: 7.9%
• Skinner series
• What is the median time to recurrence?
– Median time to recurrence is 1.5 yrs with most
recurrence occurring before 5 years
– Some cases are reported up to 20 years after
cystectomy
– That is why life long follow up is required

50. 50
What are the reasons for urethral recurrence
after radical cystectomy?
1. Unrecognised TCC in the urethra at the
time of cystectomy (synchronus TCC)
2. Growth of TCC from a positive margin of
cystectomy
3. Recurrence owing to tumor spillage /
implantation
4. De novo TCC occurrence due to field
change (metachronus)

51. 51
What are the Risk factors for urethral
recurrence?
• Prostate involvement
– Most consistent risk factor (confirmed by multiple
cystectomy series)
– Risks associated with depth of prostate involvement
(Freeman’s series)
• Prostate stromal involvement: 20%
• Superficial prostate involvement: 15%
– Some study showed no increased risk if tumor is limited
to mucosa
• No prostate involvement: 6%
– Overall 5 year survival for patient with prostatic stromal
invasion is 35%. (according to Skinner’s series)

52. 52
What are the Risk factors for urethral
Recurrence?
• Type of urinary diversion (From Skinner/Freeman series)
– Lower in orthotopic diversion
• Cutaneous diversion 11.1%
• Orthotopic diversion: 2.9%
• Even in patients with prostate involvement
– Orthotopic diversion: 5%
– Cutaneous diversion: 24%
• Possible reasons
– Possible excretion of protective substance by ileum
– Protective effect is present when there is continued exposure of
urethra to urine
– Some systemic effect of orthopic neobladder construction
• Carcinoma in situ
• Involvement of bladder neck
– Most consistent association in women

53. 53
What are the indications of
urethrectomy?
• Positive margins at the level of urethral dissection (FZ)
• If the primary tumour is located at the bladder neck or
in the urethra (in women - Universally accepted that
en-bloc urethrectomy should be done if not for
orthotopic neobladder because this adds minimal time
and morbidity to the overall procedure), or if tumour
infiltrates the prostate stroma
• +ve resection margin anywhere in the bladder
• Tumor infiltrate into the prostate
• CIS

54. 54
Laparoscopic/robotic-Laparoscopic/robotic-
assisted laparoscopicassisted laparoscopic
cystectomycystectomy

55. 55
What is the role of laparoscopic/robotic-
assisted laparoscopic cystectomy?
• Maintain oncology efficacy of ORC, ↓morbidity,
↑recovery, ↑QoL
• Most authors have favoured an extracorporeal approach
based on currently available technology and using
intestinal segments for the urinary diversion
• 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

56. 56
Urinary diversionUrinary diversion

57. 57
Now
• Preferably:
– Continent reservoir connected to urethra
– Ileal segments (lower pressure peaks and
ease of surgical handling)

58. 58
Classification of Diversion
• Orthotopic
• Heterotopic
– Continent cutaneous
• Kock pouch – small bowel > complication – secretory diarrhea
• Mainz I pouch - Ileocecal reservoir with appendix catherterizable
pouch
• Mainz II pouch – ureterosigmoidostomy
• Mainz III - Transverse colon
• Indiana pouch - the ascending colon and a portion of the ileum
– Non-continent Cutaneous
– Diversion to GIT

59. 59
3 Principles for lower urinary
tract reconstruction
• A reservoir in which to store urine in low
pressure
• A conduit through which the urine is
conducted to the surface
• A continence mechanism

60. 60
Bladder reservoir must have:
• Able to retent 500-1000ml of fluid
• Maintenance of low pressure after filling
• Elimination of intermittency pressure
spikes
• True continence
• Ease of catheterization and emptying
• Prevention of reflux
• Skinner

61. 61
Factors influencing complication
• Patient Factors
1. Performance Status/ Co-morbidities
2. Patient /Caretaker compliance to CISC
Mobility
3. Previous RT
4. Renal function
5. Liver function
6. Body Habitus/BMI
• Bowel Factors
1. Type of intestinal segment used
2. Length of intestinal segment
3. Continent vs Continuously draining
4. Method/ extent of detubularization
5. Capacity
6. Compliance
7. Reflux or non-refluxing uretero-intestinal anastomosis
8. Type of diversion chosen

62. 62
Which Gastrointestinal
segments?
• Stomach
• Ileum
• Colon
– Colonic conduit is not preferred to ileal
conduit in renal impairment
– Colonic conduit have less risk of intestinal
obstruction compared to ileal conduit
• Appendix

63. 63
1. Stomach
• Advantage:
– Less hyperchloremic acidosis
– Reduced mucus production + UTI
• Disadvantage:
– Hematuria-dysuria syndrome (overcome with composite
urinary reservoir)
– Hyper-gastinemia
– hypochloremic Hypokalemic metabolic alkalosis
• Reduced intrinsic factor, possibly leading to vitamin B12
deficiency
• Gastric pouch ulceration
• Theoretical risk of bone demineralization
• Higher risk of malignancy

64. 64
Complication
• Gastric retention due to atony of the stomach or
edema of the anastomosis
• Hemorrhage (anastomotic site)
• Hiccups (gastric distention)
• Pancreatitis (intraoperative injury)
• Duodenal leakage
• Dumping syndrome  Steatorrhea, small stomach
syndrome
• Hypoproteinemia
• Bowel obstruction (10%)

65. 65
2. Ileum2. Ileum
• Advantage:
– Can be reconfigured as low-pressure reservoir
• Disadvantage:
– Impaired Vit B12 and Bile acid absorption (if >60cm
resected)
– Increased oxalate absorption stone formation
– HypoK, Hyperchloraemic acidosis (secrete Na HCO3)
– Osteoporosis and osteomalacia

66. 66
2.1 Ileocoecal valve2.1 Ileocoecal valve
• Controlled transport of ileal content into colon
• Rapid bowel propulsion  soft stools, diarrhoea,
malabsorption
• If the ileocecal valve be used, diarrhea, excessive
bacterial colonization of the ileum with malabsorption,
and fluid and bicarbonate loss may occur
• Decrease Vit B (32%)
• Decrease folic acid (11%)
• Metabolic acidosis (30%)
• Increase risk of renal and gall bladder stones

67. 67
3. Colon3. Colon
• Advantage:
– mobile sigmoid (easy to brought down)
– Larger diameter
– Less Vit B12 and bile salt absorption problem
– results in fewer nutritional problems
– incidence of postoperative bowel obstruction with colon is 4%,
less than that occurring with ileum
– An antireflux ureterointestinal anastomosis by the submucosal
tunnel technique is easier to perform with use of colon
• Disadvantage:
– Hyperchloremic hypokalemic Metabolic acidosis
– Frequent night time voiding (enhance peristalsis + higher
pressure)
– Increased UTI and malignancy (nitrosamine)

68. 68
JejunumJejunum
• Not usually employed due to severe
electrolyte imbalance
• Hyponatremia
• Hyperkalemic Hypochloremia metabolic
acidosis
• Severe dehydration

69. 69
4. Appendix
• Useful for catheterizable nipple for
continuent cutaneous diversion
• If appendix not available  Monti pouch
with ileal segments

70. 70
Summary
• 1. Jejunum
• Salt loss syndrome (dehydration, hyponatraemia,
hypochloraemia, hyperkalaemia, metabolic acidosis).
• 2. lleum
• Salt loss syndrome
• Hyperchloraemic acidosis
• 3. Colon
• Hyperchloraemic acidosis
• 4. Bone disease
• Demineralization (long-term)
• Reduced growth (young patients)
• Increased fracture rate
• Pain in weight-bearing joints

71. 71
Preparation of ureter
• Preserve blood supply: periureteral
adventitial tissue (reduce ischemia and
stricture
• Left ureter moved across retroperitoneum
above level of IMA

72. 72
(Transuretero-) Ureterocutaneostomy
• Indications:
– After palliative cystectomy in elderly frail pt
– Temporary diversion when GI tract not possible
– Diversion for fistula or hemorrhage
• Procedure:
– Ureter mobolized to bladder  ligated and divided
– V or U shaped skin incision
– Track throught abd wall in most direct line
– Ureter with largest diameter pulled thru track (spatulated)
– Apex of skin flap to ureteral apex (4-5/0)
– The other ureter End-to-side to complete TUU
– Oemntal flap to secure anastomosis and abdominal tunnel

73. 73
Ileal conduit
• Ileal Conduit still the standard for urinary
diversions
• Wide facial opening (x-type incision)
• Ileum in isoperistaltic fashion
• Stoma site
– Above or below the waist band
– Not close to umbilicus , through the belly of
rectus , bony prominence or scar
– Be test with patient and marked pre-op

74. 74
Submucosal tunneling

75. 75
Ureteric implantation
• Bricker and Nesbit:
o Both ureter implant individually in an end-to-side
• Wallace 66:
o Paralllel orientated ureter
o Spatualted at distal end
o Posterior plate suture
o Side-to-end fashion to ileal stump
• Wallace 69:
o End to end oriented ureter
o Spatulated and suture
o Side-to-end fashion to ileal stump

76. 76
Bricker

77. 77
Wallace

78. 78
Pros and Cons
• Advantage:
o Short segment use limited metabolic change
o Suitable in renal or hepatic insufficency
o Use when post-op radiation necessary
• Contraindications:
o Short bowel syndrome
o Radiation to terminal ileum
o Ascites

79. 79
Complications of ileal or colon
urinary diversion
• Early
– Anastomotic leak, enteric fistula, bowel obstruction, ileus, conduit
necrosis, urinary leakage
• Late
– Stomal prolapse, retraction, parastomal hernia, conduit stenosis-ileal
conduit only
– uretero-ileal stenosis
– UTI (colonization of ileal conduit)
– 25% Upper tract deterioration (reflux, chronic bacteriuria)
– Upper tract calculi
– Entero-conduit fistulae
– Metabolic ↑Cl metabolic acidosis, B12, bile acids
• HyperChloremic Metabolic Acidosis (10%)
• Secondary to RTA with derange RFT
• Txn: Oral sodium bicarbonate
• Cx: Bone demineralization

80. 80
Continent urinary diversion
• Good Reservoir
– Good capacity
– Lower pressure storage
– Low metabolic issue
• Spherical reservoir: low end-filling
pressure with maximum radius
• M/ W/ U folded reservoir

81. 81
Continent catheterizable
reservior
• Indication:
– External urethral sphincter sparing surgery
impossibile
– Urethral malformations
– Spinal injury or complex neurological defects
• Patient compliance is of utmost
importance
• Risk of perforation or bladder rupture

82. 82
• Continence mechanism:
– Appendix (Mitrofanoff)
– Tapered ileum (Monti)
– Intussucepted ileal nippples

83. 83
Complications
• Re-operation rate: 22-49%
• Stomal stenosis: 4-15%
• Incontinence rate: 3.2%
• Ureteral stenosis : 8%
• Metabolic (if IC valve & terminal ileum):
diarrhoea, hyperchloraemic acidosis,
malabsorbtion

84. 84
Orthotopic neobladder
• EUS must be intact
• To rule out cancer infiltration:
– Pre-op cystoscopy+ bx of BN/ Prostatic
urethra
– Intra-op FS of resected margin
• Advantage:
– Good QOL (physical integrity)
– Near normal voiding and continence

85. 85
CI to neobladder

86. 86
Neobladder construction

87. 87
Afferent anastomosis
• Reflux prevention:
– Camey-Le Duc
– Intussuceptive ileal nipple (Hemi-Kock)
– Abol-Enein, Stein : Serosa-lined extramural
tunnel implantation
– Isoperistaltic tubular limb

88. 88
Efferent anastomosis
• Day time continence: 87-98%
• Night time continence: 72-95%
• Need of CISC: M 4%, F 15%
• Precise preparation of urethra is essential
• Avoid Corner of pouch to urethra
anastomosis kinking and difficulties with
voiding

89. 89
Uretero (ileo-)Sigmoidostomy
• Largely replace by conduits
• Main Disadvantages:
– Metabolic acidosis
– Renal failure
– Tumourigenesis (adenoCa) at site of
anastomosis
– Bacterial reflux (Pyelonephritis and ureteric
stenosis)

90. 90
What are the advantages and
disadvantages of end and loop ileal
conduit stomas?
• Advantage of loop ileal conduit
– Ease of obtaining everted bud above skin
level
• Disvantage of end ileal conduit
– More prone of ischemic complication

91. 91
What is the effort of emptying
bladder after neobladder?
• Abdominal straining, intestinal peristalsis
and sphincter relaxation

92. 92
Prognosis afterPrognosis after
cystectomycystectomy

93. 93
What are the prognostic factorsWhat are the prognostic factors
of survival post cystectomy?of survival post cystectomy?
• Age
• Pathological stage
• Positive margins
• LN status
– Herr, et al
– Single node involvement have similar survival to node
negative patients
• Molecular markers
– P53 nuclear accumulation
– Loss of p21 expression

94. 94
What is the recurrence-freeWhat is the recurrence-free
survival rate after cystectomy?survival rate after cystectomy?
5 year 10 year
P0 N0 92% 86%
Pis N0 91% 89%
Pa N0 79% 74%
P1 N0 83% 78%
P2/3aN0 78-89% 76-87%
P3b N0 62% 61%
P4 N0 50% 45%
LN+ 35% 34%
• 10 years recurrence free survival: 60%, overall survival 40%
• Stein + Skinners group USC 2001 1054 patients
J Clin Oncol. 2001 Feb 1;19(3):666-75

95. 95
T2 T3 T4
5yr OS for radical
cystectomy
60-80% 30-60% >20%
5yr OS for
radiotherapy
40% 30% 10%

96. 96
• What are the other results drawn from
Skinner’s series?
• Overall ~30% of cancers recurred
• 22% distant and 7% local recurrence
• Median time to recurrence = 12 months
• A large series of cystectomies from Johns
Hopkins has recently reported a 7% incidence of
pT0
J Clin Oncol. 2001 Feb 1;19(3):666-75

97. 97
Palliative cystectomy for
muscle-invasive bladder
carcinoma

98. 98
What is the indication of palliative
cystectomy for muscle-invasive
bladder carcinoma?
• Primary radical cystectomy in T4b bladder
cancer is not a curative option
• If there are symptoms, radical cystectomy
may be a therapeutic/palliative option
• Intestinal or non-intestinal forms of urinary
diversion can be used with or without
palliative cystectomy
• Morbidity of surgery and quality of life
should be weighed against other options

99. 99
Neoadjuvant RT

100. 100
What is the role of neoadjuvant
RT?
• No role in improving survive
• Improved local control in T3b(10%)
• Tumour downstaging after 4-6 weeks
(50%)
• Preoperative radiotherapy cannot reduce
local recurrence after radical cystectomy

101. 101
What are the means of Bladder
preserving strategies
• Definitive RT
• Definitive Chemo
• Radical TURBT + systemic chemo
– Little data, not mainstream
• Palliative TURBT +/- RT : for elderly unfit
• Partial cystectomy +/- neo-adj chemo
• TURBT + definitive RT

102. 102
What is the role of TUR alone for
muscle invasive tumor?
• TUR alone is not a curative treatment
option in most patients
• If tumour growth is limited to the
superficial muscle layer and if restaging
biopsies are negative for residual tumour,
without hydronephrosis or CIS
• Therapeutic option, when the patient is
unfit for cystectomy or refuses open
surgery

103. 103
What is the role of EBRT?
• Cochrane analysis - cystectomy has an overall survival benefit compared to radiotherapy
• Target field: bladder only with 2cm margin
• Dose: 60-66Gy
• Indication:
– Should only be considered as sole txn when the patient is unfit for cystectomy or a
multimodality bladder-preserving approach
– Can stop bleeding from the tumour when local control cannot be achieved by transurethral
manipulation because of extensive local tumour growth
– For metastasis bone pain (30Gy) or palliative RT (40Gy)
– SCC and adenocarcinoma do not respond to RT
• Result:
– 3y local control rate: 50%
– Overall 5-year survival rates : 30%- 60% (inferior to RC)
– 5 yr Cancer-specific survival rate of 20% - 50%, with or without a complete response following
radiotherapy, respectively (EAU)
– Preserve bladder function in 50% of cases, esp in low volume/minimal residual disease
• Complication:
– 3-5% required cystectomy for complication
– 50% ED
– <5% major long term GU, GI morbidity
• Important prognostic factors
– Age, tumour size/stage, hydronephrosis and the completeness of the initial TURBT
• Previously RT patient undergoing RC later have a higher risk of early complication

104. 104
Definitive Chemo
• Chemotherapy alone rarely produce
durable complete response of the primary
tumor
• Radical TURBT + Chemo may allow long
term survival with intact bladder
• EAU 2011: cannot be recommended for
routine use

105. 105
Bladder sparing treatmentBladder sparing treatment
• Bladder preservation protocol
– A comparable long-term cancer specific survival rate of 50-60%
at 5 years’ follow-up is reported by both multimodality bladder-
preserving trials with negative tumor bed and cystectomy series.
– However, both therapeutic approaches have never been directly
compared and patients in multimodality series are highly
selected.
– A bladder-preserving multimodality strategy requires very close
multidisciplinary co-operation and a high level of patient
compliance.
– Even if a patient has shown a complete response to a
multimodality bladder-preserving strategy, the bladder remains a
potential source of recurrence
– Rodel et al (the largest series)
• 415 patients, TURBT + Chemo + XRT
• 40% 5 years overall survival

106. 106
What is the role of Multimodality
treatment?
• Methrotrexate, cisplatin and vinblastine
(MCV) aims at the eradication of
micrometastasis in combination with
radiotherapy, following TURBT, results in
a complete response rate of two-third
• Salvage rates of one-third
• Delay in surgical therapy can compromise
survival rates

107. 107
Adjuvant chemotherapy

108. 108
What is benefit of adjuvant
chemotherapy?
• After accurate pathological staging
• Overtreatment is avoided
• No delay in definitive surgery

109. 109
What is the disadvantage of
adjuvant chemotherapy?
• Assessment of in-vivo chemosensitivity is not possible
• Delay of chemotherapy, due to post-operative morbidity
• Adjuvant chemotherapy is under debate
• Neither randomized trials nor a meta-analysis supported
adjuvant chemotherapy
– No benefit for N0M0 patients
– Patients with lymph node metastasis or T3/4 disease appear
to benefit most
– Adjuvant chemo MAY delay progression
– No difference in overall survival at 5 years
• Adjuvant chemotherapy is advised within clinical trials, but
not for routine use because it has not been studied
sufficiently

110. 110
ChemotherapyChemotherapy
• Accelerated MVAC – 2 weekly regimen for
3 cycles (overnight as using diuretics to
increase U/O so as to reduce the toxicity

111. 111
Metastatic Ca BladderMetastatic Ca Bladder
• Advance CaB is a chemosensitive tumor
• 10-15% metastatic disease
• Metastatic disease died in 3-4 months without
treatment
• Treatment depends on Prognostic factors:
– 2 most important :KPS (Karnofsky PS) + visceral
metastasis i.e. Bajorin prognostic factor
– Age
– RFT (obstruting disease or chronic upper tract
inflammation)
– Metabolic change post urinary diversion
– Comorbidity

112. 112
Chemo for fit pt
• Prolong survival : MVAC 14.8mon vs GC 13.8mon
• GC : Gemcitabine + cisplatin
• M-VAC: Methrotrexate, vinblastine, adriamycin + cisplatin
• Response rate up to 70%
• GC less toxic (regimen of choice), or use HD-MVAC + GCSF
– Less neutropenic fever
– Less mucositis
– Less fatique
– More anaemia
– More thrombocytopenia
• 5y survival:
– LN only disease 20%
– Visceral metastasis 7 %
• Conclusion: 1st
line txn for fit patient  cisplatin containing
combination (GC or M-VAC) preferably with GCSF (granulocyte-
stimulating colony factor

113. 113
Cisplatin
• Alkylating agent
• Form reactive molecular species that alkylate
nucleophilic groups on DNA bases, particularly
the N-7 position of guanine
• This lead to cross-linking of base, abnormal
base sparing and DNA strand breakage
• Impaired DNA synthesis, interfering mitosis,
cause cell death/apoptosis
• SE: nephrotoxicity, neurotoxicity, ototoxicity,
N/V, e- disturbance: hypomagnesaemia,
hypokalaemia and hypocalcaemia

114. 11401/07/11
Gemicitabine
• Nucleoside analog
• Triphosphate analogue of gemcitabine replaces one of
the building blocks of nucleic acids(cytidine), during
DNA replication. The process arrests tumor growth, as
only one additional nucleoside can be attached to the
"faulty" nucleoside, resulting in apoptosis.
• Another target of gemcitabine: ribonucleotide reductase
(RNR). The diphosphate analogue binds to RNR active
site and inactivates the enzyme irreversibly. Once RNR
is inhibited, the cell cannot produce the
deoxyribonucleotides required for DNA replication and
repair, and cell apoptosis is induced

115. 115
• Chemotx for unfit pt
– 50% pt unfit due to poor PS, impaired RFT, co-morbidity forbids
high volume hydration
– Carboplatin combination (Carbo +Gemzar) or M-CAVI
– M-CAVI: Methrotrexate, Caboplatin + vinblastine
– Carbo/Gem : less toxic (13% vs 23%) , more response (42% vs
30%)
• Second line agent
– Vinflunine: 3rd
generation vinca alkaloid, highest level of evidence
ever reported (Gr A recommendation in EAU guideline)
– Overall response rate 8% but significant survival benefit
– Others treatment should take plase in clinical trial:
• Bone metastasis
– In 30-40% pt
– Zoledronic acid: the only bisphosphonate approved for
metastatic bone disease
– Reduce and delay skeletal related events, improve QoL and 1y
OS

116. 116
Palliative chemotherapyPalliative chemotherapy
• First-line treatment
–CMV  RR 56%; median OS 8 months
(JCO 1985)
–M-VAC  RR 72%, CR 18%; median OS 13
months (JCO 1997)
–Gemcitabine, cisplatin (c/w M-VAC)  RR
46% (49%); median OS 13.8 months (14.8
months) (JCO 2006)

117. 117
Palliative chemotherapyPalliative chemotherapy
• First-line treatment
– Paclitaxel, gemcitabine, cisplatin (c/w GC)  ORR
57.1% vs 46.4% (p=0.02); median OS 2.9 months
longer (ASCO 2007)
– Can carboplatin replace cisplatin?
• Carboplatin-based regimens in patients with normal RFT
have ORRs in the range of 30-40%
• But CR rates are lower
• Shorter median OS of 8-10 months
• Only be used when RFT not fit for cisplain

118. 118
Palliative chemotherapyPalliative chemotherapy
• Second-line treatment
–Ifosfamide  ORR 20% (CR 9%, PR 11%)
(JCO 1997)
–Paclitaxel, weekly  ORR 10% (PR 10%); MS
7.2m (JCO 2002)
–Docetaxel  ORR 13% (PR 13%); MS 9m
(BJC 1998)
–Pemetrexed  ORR 28% (CR 6%, PR 21%);
MS 9.6m (JCO 2006) √

119. 119
Palliative chemotherapyPalliative chemotherapy
• Novel agents
– Trastuzumab + paclitaxel, carboplatin and
gemcitabine (ASCO 2005)
• Phase II trial of 32 HER2-positive patients
• RR 73%
• But survival similar to combination without Trastuzumab
– Bevacizumab + GC (ASCO 2009)
• Phase II trial
• ORR 58% (CR 14%, PR 44%)
• Stable disease 30%
• DVT/PE 21 %, 42% stopped chemotherapy due to
toxicities

120. 120
What is QOL for different forms of treatment for
invasive bladder tumor?
• No randomized prospective HRQL study
• The overall HRQL after cystectomy
remains good in most patients, whichever
type of urinary diversion is used
• Some data suggests that continent
diversions produce a better HRQL
– Body image, social, sexual and physical
function

121. 121
What is the evidence of urethral
surveillance after cystectomy?
• Urethral washes and cytology are not
recommended
– MSKCC
– They review 24 patients who had urethral
recurrence
• followed by routine urethral wash cytology
• those not followed by urethral wash cytology and
presented with bleeding or urethral discharge
• No significant survival difference in patients
followed and not followed with urethral washing

122. 122
What is the treatment of urethral
occurrence?
• Standard treatment remains total urethrectomy
• Subtotal urethrectomy sparing the meatus
– Has been abandoned
• 27% of glanular urethra involvement rate in total
urethrectomy series
• Documented reports of late recurrence at urethral meatus
• In patients with orthotopic diversion
– Can attempt endoscopic management +/-intravesical therapy
– Or neobladder has been reconstructed
• CIS in the urethra > BCG instillations have shown success rates of
80%
• In distant disease > systemic chemotherapy

123. 123
What is the Survival data regarding
patients with urethral recurrence?
• Survival after urethral recurrence has
generally been disappointing
• Median survival : 28 months
• Invasive disease and symptomatic
presentation may carry a worse prognosis

124. 124
Upper tract recurrenceUpper tract recurrence

125. 125
What is the incidence of upper
tract involvement?
• <5% of patients with bladder ca
• 1-2% may be bilateral
• Following radical cystectomy UUT occur typically
after 3 years
• Majority of UUT occur in patients who have been
treated with radical cystectomy for organ
confined disease
– This may purely reflect the poorer outcome of patients
with extravesical involvement who therefore do not
survive long enough to develop UUT
• Risk factors - intramural ureteric involvement
and CIS