Muscle invasive bladder cancer

Amar Mohee, Jen GrahamProf. Noel Clarke

21/03/14

(utilising amended slides from S. Bromage/S. Maddineni)

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

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

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

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

• <15% of patients with MIBC survive 2 yrs if left untreated

Pathogenesis

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

Staging (TMN 2009)

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

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 Doesn’t 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

• Big advantage of cystectomy over bladder-sparing treatment is ability to provide accurate pathological stage to guide adjuvant treatment

Staging MCQ• Which of the following is NOT true with regard

to staging of invasive bladder cancer?

a) Bimanual exam is highly predictive for extravesical disease if a mass is palpable after TUR

b) CT and MRI are equivalent for prediction of nodal involvement

c) Bone scanning is useful for screening asymptomatic patients with clinically organ-confined disease

d) PET scanning is limited by concentration of fluorodeoxyglucose in the lumen of the bladder

• Answer : c

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

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%

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 >8mm for pelvic nodes >10mm for abdominal nodes

•Role for FDG-PET/CT▫Sensitivity of 70%, specificity 96% (Kibel,

2009) in patients with negative CT scans

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

Case study - MS

•Histology confirms G3 muscle invasive urothelial carcinoma

•CT chest/abdo/pelvis▫Normal except for thickening of bladder

wall

•What next?

Treatment

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

Treatment

Neo-adjuvant chemotherapy

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 > 2 and/or impaired renal function.

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)

Nordic Trial 1neoadjuvant chemo+Rxcystectomy

•311 patients: locally advanced bladder cancer (G3T1-T4NxM0)▫2 cycles comprising cisplatin+doxorubicin, 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 (p=0.002)▫OS improved in all groups but not statistically▫Better OS in responders than non-responders

Scand J Urol Nephrol. 1993;27(3):355-62.

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%): p=0.001

•No statisitical survival benefit but significant downstaging

Scand J Urol Nephrol. 2002;36(6):419-25.

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.

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 1;29(16):2171-7. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18.

Neo-adjuvant chemotherapy

•Assessing responders▫PET, MRI, biomarkers▫No definite modality

•Disadvantages▫Who are responders?▫Surgical morbidity?

N Engl J Med 2003 Aug;349(9):859-66.

Treatment

Radical Cystectomy

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

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

Treatment timing•Several studies show worse outcome if

time between initial diagnosis and cystectomy >12 weeks▫More advanced pathological stage▫Decreased survival

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

5yr recurrence

free survival

5 yr overall survival

All patients (n=1054)

68% 60%

Organ confinedN - 85% 78%N + 46% 45%

ExtravesicalN - 58% 47%N + 30% 25%

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 Oncol2001

Oncological outcomes

•Overall 5 yrs disease-free survival of 55%

▫Ghoneim et al,J Urol, 2008

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)

Back to SM...•Young, fit, recently married , doesn’t like

the idea of a stoma•T2N0M0

a) Should have a preoperative bone scanb) Is not a candidate for bladder

preservation on the basis of agec) Has approx 5% risk of positive lymph

nodes at the time of cystectomyd) Should have ureteral frozen section

analysis at the time of cystectomy

Answer (according to Campbell’s) : d

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

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

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

Prostate/sexual-function sparing cystectomy• Theorectical advantage of retained sphincter and

erectile mechanisms• Usually constitutes prostate capsule sparing

(TURP or Millen’s)• Vallencien, J Urol 2002

▫ Excellent results for continence (>90%) and potency (>80%)

• 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)

Cystectomy

Lymphadenectomy

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

Lymphadenectomy: Questions

1. Does lymphadenectomy improve survival?

2. What are the Indications for lymphadenectomy?

3. What should the extent of lymphadenectomy be?

4. Does limited or extended lymphadenectomy impact on morbidity?

5. Is there a role for frozen section in 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

Lymphadenectomy

Lymph Node: where?

•Autopsy study▫215 patients with MIBC

92% peri-vesical LN 72% retroperitoneal LN 35% abdominal LN 47% N+ve and M+ve

•Pelvic nodes neg = no disease outside pelvis

Urol Int 1999;62(2):69-75.

• 25% of cystectomy specimens contain pos. nodes

• Node positivity correlates closely with T-stage▫ T1 : < 10%▫ T3-T4: 33%

• But ▫ Is survival in extended lymphadenectomy

increased directly (surgery) or indirectly (chemotherapy)?

Lymph Nodes and staging

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 <3%

Stein et al J.Clin.Oncol. (2001) 19: 666

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

Standard v. extended pelvic lymph node dissection IMA

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 Sep;60(3):572-7. doi: 10.1016/j.eururo.2011.05.062. Epub 2011 Jun 12.

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

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

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)

    No. Retrieved Nodes No. Involved Cases Pos Nodes

Region

Total Mean ± SE Total Mean ± SE

1 Paracaval group 550 2.75 ± 1.9 9 0.19 ± 0.53

2 Inter-aortocaval 846 4.23 ± 2.7 23 0.48 ± 1.35

3 Para-aortic 979 4.90 ± 2.9 40 0.83 ± 2.33

4 Rt common iliac 789 3.97 ± 2.3 34 0.71 ± 1.73

5 Lt common iliac 1,015 5.07 ± 2.8 50 1.04 ± 2.38

6 Rt external iliac 742 3.71 ± 2.6 15 0.31 ± 0.85

7 Lt external iliac 732 3.66 ± 2.9 26 0.54 ± 1.81

8 Presacral 723 3.62 ± 2.2 22 0.46 ± 1.27

9 Rt obturator 1,309 6.54 ± 3.6 62 1.29 ± 2.11

10 Lt obturator 1,202 6.01 ± 3.4 39 0.81 ± 1.79

11 Rt internal iliac 607 3.04 ± 2.9 38 0.79 ± 1.52

12 Lt internal iliac 628 3.14 ± 2.7 30 0.65 ± 1.26

LYMPH NODE INVOLVEMENT AND BLADDER CANCER

Anatomical distribution of retrieved and positive nodes

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

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

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

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 Jun;112(11):2401-8• Increases the identification of LN+ pts

▫ (common iliac and presacral nodes)

Viva Questions...

•Consent SM for radical cystectomy and urinary diversion/neobladder

Complications after RC• 3% perioperative mortality (Stein, 2001)• Morbidity (Ramani et al, BJUI 2009)

▫ Early complications – 38.6%▫ Late (>30day) – 26.9%

• Surgical complications can relate to cystectomy, LN dissection, bowel anastomosis or diversion:▫ Paralytic ileus is common▫ SBO or anastomotic leak <8.7%▫ Symptomatic lymphocoele <5%▫ Transfusion rate can be up 66%

• Medical complications▫ PE/DVT <5%▫ Also cardiac, respiratory, infectiousGakis et al, Eur Urol 2013

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)

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

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?

Radiotherapy

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.

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 Nov;74(10):2819-27Int J Radiat Oncol Biol Phys 1995 May;32(2):331-40.Cancer 1988 Jan;61(2):255-62 Cancer 1982 Mar;49(5):869-973J Urol 1997 Mar;157(3):805-7

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 May;18(3b):1931-4.

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: OS:30-60% , Cancer specific survival 20-50%• Cystectomy has survival benefit over EBRT

• Chung et al (Urol Oncol 2007 Jul-Aug;25(4):303-9)

▫340 patients with MIBC ▫ EBRT, ERBT+chemo, 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)

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

Adjuvant Chemotherapy

•For T3/4 N+ve 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

Multimodality bladder-preserving treatment

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.

Predictors of outcome

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

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

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

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

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 met’s in 38%

Follow-up

Follow-up

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.

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 GFR< 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)

Palliative Management

Control of Symptoms - Inoperable tumours (T4b)

•Palliative cystectomy ▫Not curative ▫Last resort for relief of debilitating

symptoms▫Increase mortality and morbidity

BJU Int. 2005 Jun;95(9):1211-4

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 Sep;66(3):531-5

• Bleeding and pain▫ Stop anticoagulation▫ 1% Silver nitrate, 1-2% alum, 4% formalin (painful)

J Urol 1985 Jun;133(6):956-7▫ Rx: improvement pain 59%, bleeding 73%

Clin Oncol (R Coll Radiol) 1994;6(1):11-3▫ Embolisation:?up to 90% success

Urol J 2009 Summer;6(3):149-56

Summary

•Prognosis▫Similar for radiotherapy vs radical

cystectomy▫5 year survival

T2 : 64% T3/4: 39%

•Cystectomy 30 day mortality <3% Morbidity 33% Ureteric margins : frozen section not needed

Urethra ; positive frozen section only contraindication to neobladder BUT practice varies

Summary•Lymph node dissections

Gold standard ; extended Skip lymph node met’s 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▫86%recurrences occur in first 3 years

The end