Muscle invasive bladder cancer

1
Muscle invasive bladder cancer

• Amar Mohee, Jen Graham
• Prof. Noel Clarke
• 21/03/14
• (utilising amended slides from S. Bromage/S.
  Maddineni)

2
Muscle Invasive Bladder Cancer

• Case study
• Diagnosis/staging
• Prognosis
• Treatment
• Neoadjuvant chemotherapy
• Cystectomy
• Extent in men/women
• Lymph node dissection
• Viva question Consent for cystectomy/ileal
  conduit/neobladder
• Viva question types of urinary diversion and
  their problems
• Radiotherapy
• Adjuvant/palliative chemotherapy
• Follow-up after radical treatment

3
Case Study - SM

• A 47 yrs male presents as an emergency with
  visible haematuria
• PMH nil
• Previous heavy smoker
• CT-U
• Normal upper tracts
• Filling defect in bladder
• Flexible cystoscopy shows a large solid-looking
  bladder tumour on the posterior wall

4
Risk factors

• Much the same as NMIBC
• Smoking, occupational exposure, chemotherapy
• ?particularly relevant to MIBC
• Chronic infection (particularly SCC)
• Foreign bodies including indwelling catheters
• Gender
• women more likely to be diagnosed with a primary
  MIBC (85 vs 51)
• ?hormonal role
• And present at older age
• ?due to late diagnosis haematuria mistaken for
  PV bleeding etc

5
MIBC

• 20-30 of bladder cancer is muscle invasive at
  initial diagnosis
• 15-20 of non-muscle invasive disease progresses
  to become muscle invasive
• 80 of MIBC have no history of NMIBC
• CIS may be pre-invasive lesion
• 80 progress to invasive TCC without treatment
• lt15 of patients with MIBC survive 2 yrs if left
  untreated

6
Pathogenesis
7
Diagnosis

• Requires a good TURBT with a second TUR in
  indicated cases
• Careful documentation of tumour site, size,
  number and appearance
• Biopsy of prostatic urethra or bladder neck
  recommended if
• considering neobladder
• or in suspicion of involvement
• bladder neck tumour, CIS present or multiple
  tumours
• But, frozen section analysis of urethral margin
  at time of cystectomy may be more accurate

8
Staging (TMN 2009)
9
Staging

• Understaging is a major problem (34-64 of cases)
• 1/3 of patients with MIBC have undetected
  metastasis at time of treatment for the primary
  tumour
• 25 undergoing radical cystectomy are found to
  have lymph node involvement at the time of
  surgery
• 27 of T1 tumours upstaged after cystectomy
  (Chang et al 2001)
• Herr et al (2007)
• 701 patients with T1 disease on first TUR, 30
  had T2 disease on second TUR
• 40 upstaged if no muscle in the original
  specimen
• 15 upstaged if muscle present

10
Staging pathology

• In MIBC all cases are high grade
• Morphological subtype can help assess prognosis
• Urothelial carcinoma
• Urothelial carcinoma with squamous/glandular
  differentiation
• Nested variant
• Rare but aggressive
• Micropapillary differentiation
• Frequently associated with lymphovascular
  invasion
• Doesnt respond well to neoadjuvant chemo
• Trophoblastic differentiation
• Small cell carcinoma
• May be associated with paraneoplastic symdromes
• Very sensitive to chemotherapy
• Spindle cell carcinoma
• Differentiation between pT2a/b not possible on
  TUR specimens
• important to note after cystectomy
• predictive of risk of recurrence in node
  negative disease

11
Staging MCQ

• Which of the following is NOT true with regard to
  staging of invasive bladder cancer?
• Bimanual exam is highly predictive for
  extravesical disease if a mass is palpable after
  TUR
• CT and MRI are equivalent for prediction of nodal
  involvement
• Bone scanning is useful for screening
  asymptomatic patients with clinically
  organ-confined disease
• PET scanning is limited by concentration of
  fluorodeoxyglucose in the lumen of the bladder
• Answer c

12
Staging Radiology

• Aims to determine
• Extent of local disease
• Evaluate upper tracts
• Lymph node involvement
• Exclude metastasis to distant organs
• Lung, liver, bones, peritoneum etc
• Gives prognostic information
• Aids appropriate treatment selection

13
Staging local extent

• Ideally before TUBRT
• Difficult to differentiate tumour and post-op
  change
• MRI reported to be more accurate than CT for
  local tumour assessment
• Both limited in detecting T3a disease so
  principal aim to detect T3b
• Accuracy for MRI 73-96
• Accuracy for CT 55-92

14
Staging lymph nodes

• CT/MRI generally equivalent
• Sensitivity 48-87
• Assessment based on size
• Poor for assessing metastasis in minimally
  enlarged nodes
• Suspicious if max short axis diameter
• gt8mm for pelvic nodes
• gt10mm for abdominal nodes
• Role for FDG-PET/CT
• Sensitivity of 70, specificity 96 (Kibel, 2009)
  in patients with negative CT scans

15
Staging upper tracts/distal mets

• Excretory phase CT-U highest accuracy for
  diagnosing upper tract disease
• Sensitivity 67-100
• Specificity 93-99
• CT/MRI generally equivalent for distal abdominal
  mets but CT may be better for lung mets
• Bone scan
• Useful in highest risk disease
• If symptomatic of bony pain
• Raised Alk phos
• But MRI may be better for detecting bony disease
• Role for FDG-PET/CT?
• Mertens et al, BJUI 2013
• 19.8 upstaged
• 8/96 found to have second primary
• Additional info influenced treatment option in
  20
• Not recommended by EAU at present

16
Case study - MS

• Histology confirms G3 muscle invasive urothelial
  carcinoma
• CT chest/abdo/pelvis
• Normal except for thickening of bladder wall
• What next?

17
Treatment
18
Basic principles

• Aim for
• Long term survival
• Prevention of pelvic recurrence or metastatic
  bladder cancer
• Excellent QoL
• 2 concepts of curative treatment
• Radical cystectomy /- systemic chemotherapy
• Bladder conserving therapy TURBT, radiotherapy,
  systemic chemotherapy

19
Treatment

• Neo-adjuvant chemotherapy

20
Neo-adjuvant chemotherapy

• Evidence
• Neoadjuvant cisplatin-containing combination
  chemotherapy improves overall survival.
• Neoadjuvant chemotherapy has its limitations
  regarding
• patient selection
• current development of surgical technique
• current chemotherapy combinations.
• Recommendations
• Neoadjuvant chemotherapy is recommended for
• T2-T4a, cN0M0 bladder cancer
• and should always be cisplatinum-based
  combination therapy.
• Neoadjuvant chemotherapy is not recommended in
  patients with PS gt 2 and/or impaired renal
  function.

21
Background

• Cystectomy alone 50 OS in 5 years
• Neo-adjuvant chemotherapy
• Better tolerated preop
• Burden of micromets less
• Improve pathological status (less positive
  margins and nodes)

22
Nordic Trial 1neoadjuvant chemoRx?cystectomy

• 311 patients locally advanced bladder cancer
  (G3T1-T4NxM0)
• 2 cycles comprising cisplatindoxorubicin, with a
  3-week interval between cycles 1 and 2 vs no
  chemo
• 4Gy for 5 consecutive days, then cystectomy
• 18/12 FU (47/12 for alive patients)
• Results in chemotherapy group (vs no chemo)
• Downstaging in T1 group (p0.002)
• OS improved in all groups but not statistically
• Better OS in responders than non-responders

Scand J Urol Nephrol. 199327(3)355-62.
23
Nordic Trial 2neoadjuvant chemo ? cystectomy

• 317 patients (T2-4aNxM0)
• 3 courses of cisplatin-methotrexate vs no chemo
• 5.3 years FU
• Results
• OS 53 vs 46
• pT0 (26 vs 11) p0.001
• No statisitical survival benefit but significant
  downstaging

Scand J Urol Nephrol. 200236(6)419-25.
24
Cochrane Review 2005neoadjuvant chemo? cystectomy

• 3005 patients from 11 RCTs (T2-T4a)
• Platinum based combination chemotherapy
  significant benefit on OS
• 14 reduction in the risk of death
• 5 absolute benefit at 5 years (95 CI 1 to 7)
• OS increased from 45 to 50.
• Effect was observed irrespective of the type of
  local treatment and did not vary between
  subgroups of patients
• Combination platinum based chemo better than
  single platinum based agent

Cochrane Database Syst Rev. 2005 Apr
18(2)CD005246.
25
BA06 30894 trialneoadjuvant chemo ?cystectomy or
Rx

• 967 patients,
• 8 years follow-up
• CMV Cisplatin, methotrexate and vinblastine
• 16 reduction in the risk of death
• corresponding to an increase in 10-year survival
  from 30 to 36) after CMV

J Clin Oncol. 2011 Jun 129(16)2171-7. doi
10.1200/JCO.2010.32.3139. Epub 2011 Apr 18.
26
Neo-adjuvant chemotherapy

• Assessing responders
• PET, MRI, biomarkers
• No definite modality
• Disadvantages
• Who are responders?
• Surgical morbidity?

N Engl J Med 2003 Aug349(9)859-66.
27
Treatment

• Radical Cystectomy

28
Radical Cystectomy

• Good outcome requires
• Appropriate indication
• Standard of treatment for localised MIBC (T2-T4a,
  N0-Nx, M0)
• Also indicated for
• High risk and recurrent NMIBC
• Failed BCG
• Salvage treatment after non-response or
  recurrence after bladder-sparing therapy
• Optimisation of patient
• Adequate surgery
• Combination with chemotherapy

29
Patient selection

• Treatment choice guided by
• Performance status
• Biological age
• Data from SEER registry shows that while stage is
  important for cancer-specific death, age carries
  highest risk of other-cause mortality but not for
  increased cancer-specific death
• Pre-existing co-morbidities
• Radical cystectomy (RC) may be preferred to
  radiotherapy if
• Presence of CIS
• Upper tract obstruction
• Severe irritative urinary symptoms
• Presence of inflammatory bowel disease

30
Treatment timing

• Several studies show worse outcome if time
  between initial diagnosis and cystectomy gt12
  weeks
• More advanced pathological stage
• Decreased survival

Sanchez-ortiz et al, J urol, 2003 Gore et al,
Cancer 2009
31
Oncological outcomes

• Survival is dependent on pathological stage and
  lymph node involvement
• 86 of recurrences occur within 3yrs
• 25 local pelvic
• 75 distant
• Stein et al,
• J Clin Oncol
• 2001

5yr recurrence free survival 5 yr overall survival
All patients (n1054) 68 60
Organ confined
N - 85 78
N 46 45
Extravesical
N - 58 47
N 30 25
32
Oncological outcomes

• Overall 5 yrs disease-free survival of 55
• Ghoneim et al,
• J Urol, 2008

33
Extent of surgery

• Standard surgical technique for curative RC
• Removal of bladder and all macroscopically
  visible and resectable bladder-perforating tumour
  extensions
• removal of adjacent distal ureters
• Lymphadenectomy
• Plus
• In men
• Prostatectomy
• (urethrectomy)
• In women, standard pelvic exenteration includes
• Entire urethra
• Adjacent vagina
• Uterus
• Technical variations aim to improve QoL (preserve
  continence/sexual function)

34
Back to SM...

• Young, fit, recently married , doesnt like the
  idea of a stoma
• T2N0M0
• Should have a preoperative bone scan
• Is not a candidate for bladder preservation on
  the basis of age
• Has approx 5 risk of positive lymph nodes at the
  time of cystectomy
• Should have ureteral frozen section analysis at
  the time of cystectomy
• Answer (according to Campbells) d

35
Ureteric margins

• Traditionally ureteric margins sent for frozen
  section
• Sensitivity of 74 and specificity 99.8
• Further ureteric resection in presence of
  positive margins
• Some small series suggest that there is little
  gained by resection back to normal urothelium
• Schoenberg J.Urol 1996
• Therefore ureteric margins only sent if specific
  indication

36
Urethrectomy - men

• Urethral recurrence in 6-8
• Usually within 14-24 months of RC
• Historically, indications for urethrectomy
• multifocality, diffuse CIS, bladder neck, and
  prostate involvement
• But CIS and multifocality NOT associated with ?
  risk
• Risk ? if prostatic involvement
• 5 risk if no involvement
• 12/18 if superficial/invasive involvement
• ?risk in orthotopic diversion compared with
  cutaneous diversion (independent of prostatic
  involvement)
• Best predictive parameter is frozen section
  analysis at time of cystectomy
• Positive urethral margin indication for
  urethrectomy

Stein et al J.Urol 2005
37
Urethrectomy - women

• Urethral recurrence in 0.8-4.3
• Stein et al, Urology 1998
• Bladder neck involvement is the most important
  risk factor for urethral involvement
• Frozen section analysis shows 100 sensitivity
  and specificity for detection of a positive
  urethral margin compared with final pathology
• ?role for preserving uterus/vagina to provide
  improved anatomical support for the neobladder
  and preservation of autonomic nerves

38
Prostate/sexual-function sparing cystectomy

• Theorectical advantage of retained sphincter and
  erectile mechanisms
• Usually constitutes prostate capsule sparing
  (TURP or Millens)
• Vallencien, J Urol 2002
• Excellent results for continence (gt90) and
  potency (gt80)
• But, concerns over 10-15 increased oncological
  failure rate (Hautmann, Stein, Urol Clin North
  Am, 2005)
• Careful patient selection needed
• Incidental prostate cancer found in 28 of men
  undergoing cystoprostatectomy
• 20 of these Gleason 7 (Abdelhady, BJUI 2007)

39
Cystectomy

• Lymphadenectomy

40
Lymphadenectomy in GU Cancers

• Is it curative or diagnostic for staging
  purposes?
• Curative
• Penile
• Testicular
• Rarely curative
• Prostate
• Bladder
• Probably not curative (?prognostic)
• Renal
• Renal pelvis
• Ureteric

41
Lymphadenectomy Questions

• Does lymphadenectomy improve survival?
• What are the Indications for lymphadenectomy?
• What should the extent of lymphadenectomy be?
• Does limited or extended lymphadenectomy impact
  on morbidity?
• Is there a role for frozen section in
  lymphadenectomy?

42
Lymphadenectomy

• No improvement of PLND on survival
• Poulsen et al., J Urol, 1998
• Vieweg et al., J Urol, 1999
• Leissner et al., BJU Int 2000
• Significant improvement of PLND on survival
• Skinner, J Urol, 1982
• Poulsen et al., J Urol, 1998
• Leissner et al., BJU Int, 2000
• Mills et al., J Urol, 2001
• Herr et al., J Urol, 2002

43
Lymph Node where?

• Autopsy study
• 215 patients with MIBC
• 92 peri-vesical LN
• 72 retroperitoneal LN
• 35 abdominal LN
• 47 Nve and Mve
• Pelvic nodes neg no disease outside pelvis

Urol Int 199962(2)69-75.
44
Lymph Nodes and staging

• 25 of cystectomy specimens contain pos. nodes
• Node positivity correlates closely with T-stage
• T1 lt 10
• T3-T4 33
• But
• Is survival in extended lymphadenectomy increased
• directly (surgery) or
• indirectly (chemotherapy)?

45
Extent of lymphadenectomy

• Gold Standard Surgery
• Standard lymphadenectomy
• common iliac bifurcation, with the ureter being
  the medial border, and including the internal
  iliac, presacral, obturator fossa and external
  iliac nodes
• An extended lymphadenectomy
• aortic bifurcation
• Genitofemoral N (lat) to Obturator N (med)
  Inguinal ligament (Inf) to Aortic bifurcation
  (Sup)
• Peri-operative mortality lt3

Stein et al J.Clin.Oncol. (2001) 19 666
46
Standard v. extended pelvic lymph node dissection
1 Para-caval 2 Inter-aorto-caval 3
Para-aortic 4 Common iliac 5 Common iliac 6
Ext iliac 7 Ext Iliac 8 Pre-sacral 9
Obturator 10 Obturator 11 Int iliac 12 Int Iliac
IMA
47
Optimal extent of lymphadenopathy(Mansoura,
Egypt)

• Prospective study 400 consecutive patients
• 200 (50) received extended LN dissection (ELN)
• No neoadjuvant or adjuvant therapy
• 50/12 FU
• 96 patients (24.0) had lymph node metastases
• 5-yr disease-free survival ELN group
• 66.6 vs 54.7 (p 0.043)
• In LN Pos patients
• 5-yr disease-free survival (48.0 vs 28.2 p
  0.029)

Eur Urol. 2011 Sep60(3)572-7. doi
10.1016/j.eururo.2011.05.062. Epub 2011 Jun 12.
48
Evidence for extent of lymphadenectomy

• Leissner et al. J.Urol, 2004
• Prospective study between 1999-2002
• x6 centres
• 290 pts with invasive bladder cancer
• TCC 76, SCC 19, Adeno 3.4
• Radical cystectomy and extended PLND
• No prior neoadjuvant chemo
• All surgery performed by 2 surgeons only in each
  centre

49
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50
Site of lymph node involvement

• Abol-Enein J.Urol, 2004
• Prospective study between 1999-2002
• 200 pts with invasive bladder cancer
• TCC 115, SCC 68, Adeno 17
• Radical cystectomy and extended PLND
• No prior neoadjuvant chemo
• Pre-op staging with contrast CT
• All surgery performed by 2 surgeons

51
Nodal Statistics

• 10,122 nodes examined
• 48 (24) pts had pos. LNs
• Mean number of pos. nodes/involved case 8.08
  13.2 (range 1-56)

52
LYMPH NODE INVOLVEMENT AND BLADDER CANCER
Anatomical distribution of retrieved and positive
nodes
53
Extent of lymphadenectomy

• Dhar et al, march 2008, J.Urol
• Compared 2 institutions 1987-2000
• Cleveland clinic limited lymphadenectomy (336)
• University of Bern Extended (322)
• All staged N0M0 prior to surger
• CIS/pT1 and T4 excluded

54
Extent of lymphadenectomy

• Dhar et al, march 2008, J.Urol
• Results
• Overall positive rate
• 13 for limited vs 26 for extended
• 5 year recurrence free survival rate for N
• 7 for limited vs 35 for extended
• 5 year recurrence free survival rate for T3N0-2
• 19 for limited vs 49 for extended
• Extended dissection -
• more accurate staging
• improved survival with non organ confined node
  positive disease

55
Morbidity of lymphadenectomy

• Does extended lymph node dissection bear more
  morbidity than limited dissection?
• Controlled trial n 92, 46 standard, 46 extended
• Extended node dissection adds an hour to
  procedure.
• No difference in morbidity
• Broessner et al BJUI (2004) 93 64

56
Summary Extended PLND

• Requires increased technical expertise
• Increases the operative time by 60min
• Consequently, probably does impact on morbidity
• How many?
• Around 10-15
• Cancer. 2008 Jun112(11)2401-8
• Increases the identification of LN pts
• (common iliac and presacral nodes)

57
Viva Questions...

• Consent SM for radical cystectomy and urinary
  diversion/neobladder

58
Complications after RC

• 3 perioperative mortality (Stein, 2001)
• Morbidity (Ramani et al, BJUI 2009)
• Early complications 38.6
• Late (gt30day) 26.9
• Surgical complications can relate to cystectomy,
  LN dissection, bowel anastomosis or diversion
• Paralytic ileus is common
• SBO or anastomotic leak lt8.7
• Symptomatic lymphocoele lt5
• Transfusion rate can be up 66
• Medical complications
• PE/DVT lt5
• Also cardiac, respiratory, infectious
• Gakis et al, Eur Urol 2013

59
Mortality and case volume

• McCabe et al Postgrad Med J 2007
• Significant inverse correlation between case
  volume and mortality rate
• Minimum case load of 8 procedures per year to
  achieve the lowest mortality
• NICE recommend centres perform a combined total
  of 50 cystectomies/prostatectomies per year
• (Improving outcomes in urological cancers, 2010)

60
Minimally invasive surgery

• Lin, Br J cancer 2014
• Prospective randomised control trial of open vs
  LAP-assisted cystectomy
• 35 patients in each group
• Significant differences in
• Operative time, estimated blood loss , analgesic
  requirement, time to resumption of oral intake
• No difference in
• Length of stay, complications, lymph node yield
• Nix Eur Urol 2010
• Prospective randomised control trial of open vs
  ROBOTIC-assisted cystectomy
• Significant differences in
• Operative time, time to return of bowel function,
  analgesic requirement
• Non-inferior for lymph node yield

61
Long term complications

• May vary according to the type of urinary
  diversion
• Viva question
• Tell me different options for reconstruction
  following cystectomy. What problems can occur?

62
Radiotherapy
63
Neo-adjuvant radiotherapy

• Conclusions
• No data exist to support
• There are suggestions in older literature that
  pre-operative radiotherapy decreases local
  recurrence of muscle-invasive bladder cancer
• Recommendations
• Pre-operative radiotherapy is not recommended to
  improve survival
• Pre-operative radiotherapy for operable
  muscle-invasive bladder cancer results in tumour
  downstaging after 4-6 weeks.

64
Neo-adjuvant radiotherapy

• Retrospective studies
• pre-operative radiotherapy at doses of 40-50 Gy,
  followed after 4-6 weeks by cystectomy
• downstaging of the tumour stage (40-65 of
  patients)
• lower risk of local recurrence (10-42)
• improved survival (11-12)

Cancer 1994 Nov74(10)2819-27 Int J Radiat Oncol
Biol Phys 1995 May32(2)331-40.Cancer 1988
Jan61(2)255-62 Cancer 1982 Mar49(5)869-973 J
Urol 1997 Mar157(3)805-7
65
Neo-adjuvant radiotherapy

• Prospective studies
• X6 RCTs (Rx vs cystectomy alone)
• SWOG, Mansoura, other small ones
• No increase in toxicity
• A meta-analysis
• odds ratio for the difference in 5-year survival
  of 0.71
• ?bias largest trial, majority did not receive
  the planned treatment.
• Results of the largest trial were excluded,
• the odds ratio became 0.95 (95 CI 0.57-1.55)

Anticancer Res 1998 May18(3b)1931-4.
66
External beam radiotherapy (EBRT)

• Bladder with 2cm safety margin
• Target dose 60-66 Gy, divided daily 1.8-2.0 Gy
• 6-7 weeks max, to prevent repopulation of tumour
  cells
• Cochrane review(Cochrane Database Syst Rev
  2002(1)CD002079)
• NMIBC 5 year OS30-60 , Cancer specific
  survival 20-50
• Cystectomy has survival benefit over EBRT
• Chung et al (Urol Oncol 2007 Jul-Aug25(4)303-9)
• 340 patients with MIBC
• EBRT, ERBTchemo, neoadj chemo then EBRT
• At 10 years, cancer free survival 35, OS 19
• EBRT alone only in select patients
• No CIS, 2 year disease recurrence bad prognosis)

67
Chemotherapy

• Evidence
• Adjuvant chemotherapy is under debate.
• Neither randomised trials nor a meta-analysis
  have provided sufficient data to support the
  routine use of adjuvant chemotherapy.

68
Adjuvant Chemotherapy

• For T3/4 Nve M0 disease
• X6 trials
• Poorly designed
• No obvious benefit
• At the time of recurrence vs straight after
  surgery?
• No benefit
• Clinical trials will provide data

69
Multimodality bladder-preserving treatment
70
Tri-modality bladder-sparing therapy

• Optimal candidate is T2Nx or N0MO without
• Extensive CIS
• Tumour-associated hydronephrosis
• Tumour invasive into prostatic stroma
• Need to be motivated and undergo frequent
  cystoscopies with cystectomy if necessary for
  recurrence
• Complete response rate in 60-80
• 3 series show similar 5/10yr survival to
  cystectomy BUT
• Results confounded by clinical staging only
• Prompt use of cystectomy when neccessary

Gaskis et al, Eur Urol 2013.
71
Predictors of outcome
72
Outcome predictors

• Tumour grade and stage
• Prostatic stromal involvement
• 20 5 year survival
• Hydronephrosis pre-op
• Molecular markers
• Tumour associated antigens
• Oncogenes (c-H-ras, c-myc, c-erbB2)
• Cellular adhesion molecules (E-Cadherin)
• Blood group antigens
• Proliferating antigens
• Epidermal growth factor receptor
• Angiogenesis inhibitors

73
Quality of life

• Evidence
• The use of validated questionnaires is
  recommended to assess HRQoL in patients with
  MIBC.
• Unless a patients comorbidities, tumour
  variables and coping abilities present clear
  contraindications, a continent urinary diversion
  should be offered.

74
Quality of life

• Validated questionnaires
• Concerning physical, emotional, social functions
• e.g. FACT (Functional Assessment of Cancer
  Therapy )
• Bladder reconstruction scores higher
• not always significant
• Also used to show improvements with palliative Rx

75
QOL after urinary diversion

• Patients with continent diversion generally score
  better on-
• Body image, social activity and physical function
• Lack of significance ? Due to response shift
• Najari et al. 2007, J.Urol
• Compared 116 patients- radical cystectomy
• Neobladder (81)
• Continent cutaneous diversion (26)
• Ileal conduit (9)
• Erectile dysfunction, urinary and bowel functions
• ED improved irrespective of diversion
• Neobladder significantly more leakage and worse
  function at night

76
QOL bladder preservation

• Perdona et al 2008 Cancer
• 1994-2002
• 121 patients T2-T4
• TUR and 2 cycles of chemotherapy
• Then radiotherapy
• Survival rates at 5 years
• Overall 68
• Bladder intact 51
• Distant mets in 38

77
Follow-up
78
Follow-up
79
Follow up

• Normograms not recommended
• Most recurrences within 24 months after
  cystectomy
• 10-15 pelvic recurrence
• Up to 50 distant mets lung, liver, bones
• 1.8-6.0 upper tract recurrence
• 1/3 diagnosed by surveillance, 2/3 by symptoms
• ve margin, multi-focality, NMIBC
• 1.5-6.0 urethral recurrence in male
• Risk is lower in orthotopic diversion (?normal
  urine flow)
• Asymptomatic better survival than symptomatic

Eur Urol 2012 Aug 62(2) 290-302.
80
Follow-up of renal function

• Ileal conduit
• 29 have renal deterioration in the long term
• No surgical cause for deterioration in 18
• Important predisposing factors
• Hypertension
• recurrent urinary sepsis
• GFRlt 50 ml/min
• 11 with deterioration due to upper tract
  obstruction
• identifiable using renography and GFR
• A type IIIb curve was an early indicator of
  obstruction.
• (Samuel et al. J.Urol, vol 176, 2006)

81
Palliative Management
82
Control of Symptoms - Inoperable tumours (T4b)

• Palliative cystectomy
• Not curative
• Last resort for relief of debilitating symptoms
• Increase mortality and morbidity
• BJU Int. 2005 Jun95(9)1211-4

83
Control of Symptoms

• Obstructive symptoms
• Mechanism mechanical, invasion leading to
  altered peristalsis
• Diversion ( palliative cystectomy),
• BL nephrostomies (easiest)
• Stenting (patient choice but gets blocked and may
  migrate, frequent change)
• Urology 2005 Sep66(3)531-5
• Bleeding and pain
• Stop anticoagulation
• 1 Silver nitrate, 1-2 alum, 4 formalin
  (painful)
• J Urol 1985 Jun133(6)956-7
• Rx improvement pain 59, bleeding 73
• Clin Oncol (R Coll Radiol) 19946(1)11-3
• Embolisation?up to 90 success
• Urol J 2009 Summer6(3)149-56

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85
Summary

• Prognosis
• Similar for radiotherapy vs radical cystectomy
• 5 year survival
• T2 64
• T3/4 39
• Cystectomy
• 30 day mortality lt3
• Morbidity 33
• Ureteric margins frozen section not needed
• Urethra positive frozen section only
  contraindication to neobladder
• BUT practice varies

86
Summary

• Lymph node dissections
• Gold standard extended
• Skip lymph node mets
• Curative in small number
• Adds an hour no evidence of increased morbidity
• Send packets separately
• Variable sentinel node position
• Quality of life
• Type of diversion tailored to individual
• Follow-up after radical treatment variable
• 86recurrences occur in first 3 years

87
The end