Bladder CancerURO

8/11/2019 Bladder CancerURO

1/56

Bladder Cancer

Adam Madej M.D.

Marek Lipiski M.D. Ph.D.Associated Professor of Urology


2/56

EBM


3/56

Guidelineses

Two guidelineses = Two diseases


4/56

Epidemiology

fourth most common cancer in menmale-to-female 3.8 : 1

6.6% of the total cancers in men / 2.1% in women

2006, Europe:104,400 incident cases of bladder cancer

82,800 in men

21,600 in women


5/56

Epidemiology

Initial diagnosis of bladder cancer:

70% non-muscle-invasive

30% muscle-invasive


6/56

Risk factors

Tobacco smoking !!!

the most well-established risk factor

causing about 50-65% of male cases and 20-30% of female casesrelated to the duration of smoking

and number of cigarettes smoked per day

Occupational exposure to chemicals

work-related cases = 20-25%benzene derivatives and arylamines

Professions who use rubbers, textiles, paints, leathers and chemicals

Phenacetin


7/56

Risk factors

EBRT

external beam radiation therapy for gynaecological malignancies

Dietary factors

hypothesis; vegetable and fruit intake

reduced the risk of bladder cancer

Chronic urinary tract infection

invasive squamous cell carcinomaschistosomiasis

Cyclophosphamide

Gender


8/56

Classification

2002 TNM by UICC (Union International Contre le Cancer)


9/56

Classification

2002 TNM by UICC (Union International Contre le Cancer)


10/56

NMIBC


11/56

Histological grading


12/56

PUNLMP

The PUNLMPare defined

as lesions that do not have

cytological featuresof malignancy but show

normal urothelial cells

in a papillary configuration.

Although they have

a negligible risk forprogression, they

are not completely benign

and still have a tendency

to recur.


13/56

Morphological subtypes

Muscle-invasive bladder cancer

In this stage all cases are high-gradeurothelial carcinomas

(grade II or grade III in WHO 1973),

but some morphological subtypes can be most important

for prognosis and treatment decisions:

Small-cell carcinomas Urothelial carcinomas with squamous and/or glandular partial differentiation

Spindle cell carcinomas

Some urothelial carcinomas with trophoblastic differentiation


14/56

Diagnosis

Symptoms

Painless haematuria !!!

urgency

dysuriaincreased frequency

pelvic pain

in more advanced tumours


15/56

Diagnosis

Physical examination

rectal and vaginal bimanual palpation

A palpable pelvic mass can be found in patients

with locally advanced tumours.In addition, bimanual examination should be carried out

before and after TUR to assess

whether there is a palpable mass or the tumour fixed to the pelvic wall.


16/56


17/56

Diagnosis

Imaging

IVU intravenous urography

CT computed tomography

US ultrasonography

CT urography


18/56

Diagnosis

Imaging



US ultrasonography

CT urography


19/56

Diagnosis

Imaging



US ultrasonography

CT urography


20/56

Diagnosis

Urinary cytology

Examination of a voided urine

or

bladder-washing specimen

>>>

exfoliated cancer cells

high sensitivity

in high-grade tumours


21/56

Diagnosis

Cystoscopy

The diagnosis of bladder cancer

depends on

cystoscopic examination

of the bladderand

histological evaluation

of the resected tissue.


22/56

Diagnosis

Transurethral resection (TUR)

The goal of TUR is to make the correct diagnosis,

which means including bladder musclein the resection biopsies.


23/56

Diagnosis


Small tumours (less than 1 cm)

resection en bloc

the specimen contains the complete tumour

plus a part of the underlying bladder wall including bladder muscle

Larger tumours

resection in fractions

exophytic part of the tumour

underlying bladder wall with the detrusormuscle

edges of the resection area


24/56

Diagnosis


As a standardprocedure, cystoscopy and TUR

are performed using white light. However, the use of white light

may lead to missing lesions that are present but not visible.

Flat urothelial lesions such as dysplasia or carcinoma in situare difficult to be identified under routine cystoscopic procedures.

Small papillary tumors can be easily overlooked

during conventional white light cystoscopy.


25/56

Photodynamic diagnosis

FLUOROCHROME

hexaminolevulinate

5-ALA >>>

PROTOPORPHYRIN IXOptical filter (405 nm)

Photodynamic diagnisis (PDD) involves fluorescence to localise abnormal

tissue. This method is based on selective accumulation of fluorochrome

(hexaminolevulinate; 5-ALA) in malignant cells.


26/56

Photodynamic diagnosis

white light cystoscopy fluorescence-guided cystoscopy


27/56

Diagnosis

Bladder and prostatic urethral biopsy

The biopsies from normal-looking mucosa in patients with bladder tumours

so called random biopsies (R-biopsies)

or selected site mucosal biopsies

are only recommended if fluorescent areas are seen

with photodynamic diagnosis (PDD).

Cold cup biopsies from normal-looking mucosa should be performed

when cytology is positive,

when exophytic tumour is of non-papillary appearance,

or when fluorescent areasare seen with PDD.


28/56

Diagnosis

Second resection

when the initial resection has been incomplete

when multiple and/or large tumours are present

when the pathologist has reported that the specimencontained no muscle tissue

when a high-grade, non-muscle-invasive

tumour or a T1 tumour has been detected at the initial TUR


29/56


30/56

Prognostic factors for NMIBC

The classic way to categorize patients with TaT1 tumours

is to divide them into risk groups based on prognostic factors.

The scoring system is based on the six most significant

clinical and pathological factors:

number of tumours

tumour size prior recurrence rate

T category

presence of concomitant CIS

tumour grade


31/56


Weightingused to calculate

recurrence

and

progression

scores


32/56


Probability of recurrenceand progressionaccording to total score


33/56

Treatment

Treatment

of NMIBC


34/56

Treatment

Transurethral resection of bladder tumor (TURBT)

is the first-line treatment to diagnose, to stage,

and to treat visible tumors.

Patients with bulky, high-grade, or multifocal tumors

should undergo a second procedure

to ensure complete resection and accurate staging.

Approximately 50% of stage T1 tumorsare upgraded to muscle-invasive disease.

Electrocauteryor laser fulgurationof the bladder tumor

is sufficient for low-grade, small-volume, papillary tumors.


35/56

Treatment

High-grade T1 tumors that recur despite BCGhave a 50% likelihood of progressing to muscle-invasive disease.

Cystectomy performed prior to progression

yields a 90%5-year survival rate.

The 5-year survival rate drops to 50-60%

in muscle-invasive disease.

Patients with unresectable large superficial tumors,

prostatic urethra involvement, and BCG failure

should also undergo radical cystectomy.

Radical cystectomy in NMIBC


36/56

Treatment

BCG immunotherapy is used in the treatment of Ta, T1, and CISurothelial carcinoma of the bladder

decrease the rate of recurrence and progression

it is the most effective intravesical therapy

Mechanism: Immune response against BCG surface antigenscross-reacted with putative bladder tumor antigens

Typically, BCG is administered weekly for 6 weeks.

Another 6-week course may be administered

if a repeat cystoscopy reveals tumor persistence or recurrence.

Intravesical BCG immunotherapy

(Bacillus Calmette-Gurin immunotherapy)


37/56

Treatment

Valrubicinhas recently been approved as intravesical chemotherapy for CIS thatis refractory to BCG.

Other forms of adjuvant intravesical chemotherapy for bladder cancer include

intravesical triethylenethiophosphoramide (thiotepa[Thioplex]), mitomycin-C,

doxorubicin, and epirubicin.

Although these agents may increase the time to disease recurrence,

no evidence indicates that these therapies prevent disease progression.

No evidence suggests that these adjuvant therapies are as effective as BCG.

Intravesical chemotherapy


38/56

Treatment

Treatment

of muscle-invasive

and metastatic

bladder cancer


39/56

Treatment

The standard treatment

for patients with muscle-invasive bladder canceris radical cystectomy.

However, this gold standard

only provides 5-year survival in about 50% of patients.

In order to improve these unsatisfactory results,

the use of peri-operative chemotherapy has been explored since the 1980s.


40/56

Neoadjuvant chemotherapy

Neoadjuvant cisplatin-containing combination chemotherapy

improves overall survival by 5-7%

Neoadjuvant chemotherapy has its limitations regarding patient

selection, current development of surgical technique, and current

chemotherapy combinations.

Neoadjuvant cisplatin-containing combination chemotherapy

should be considered in muscleinvasive bladder cancer,

irrespective of definitive treatment

Neoadjuvant chemotherapy is notrecommended

in patients with PS > 2 and impaired renal function

ECOG / WHO / Z b d


41/56

ECOG / WHO / Zubrod score

0 - Asymptomatic(Fully active, able to carry on all predisease activities without restriction)

1 - Symptomatic but completely ambulatory(Restricted in physically strenuous activity but ambulatory and able to carry out work of a

light or sedentary nature. For example, light housework, office work)

2 - Symptomatic, 50% in bed, but not bedbound(Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)

4 - Bedbound(Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)

5 - Death

ECGO scorequantify cancer patients' general well-being


42/56

Radical cystectomy

Traditionally radical cystectomy is recommended for patients

with muscle-invasive bladder cancer

T2-T4a, N0-Nx, M0

Other indications include high-risk and recurrent superficial tumours:

BCG-resistant Tis,

T1G3

extensive papillary disease

that cannot be controlled with TUR and intravesical therapy alone

Indications


43/56

Radical cystectomy

Salvage cystectomyis indicated for:

non-responders to conservative therapy

recurrences after bladder sparing treatments

non-urothelial carcinomas

and as a purely palliative intervention

for e.g. fistula formation, pain or recurrent macrohematuria

Indications


44/56


45/56

U i Di i


46/56

Urinary Diversion

abdominal diversionsuch as ureterocutaneostomy, ileal or colonic

conduit, and various forms of acutaneous continent pouch

urethral diversionwhich includes various forms of gastrointestinalpouches attached to the urethra as a continent, orthotopic urinary

diversion (neobladder, orthotopic bladder substitution)

rectosigmoid diversions, such as uretero(ileo-)rectostomy.

From an anatomical standpoint three alternatives

are presently used after cystectomy:

U i Di i


47/56

Urinary Diversion

Ureterocutaneostomy

U i Di i


48/56

Urinary Diversion

Ileal conduit

Continent cutaneous

urinary diversion

C l d it


49/56

Colon conduit

U i Di i


50/56

Urinary Diversion

Ureterocolonic

diversion

Orthotopic neobladder

VESICA ILEALE PADOVANA (VIP)


51/56

( )


52/56

R di l t t


53/56

Radical cystectomy

Treatment


54/56

Treatment

Treatment

of non-rescetable

tumors

Treatment


55/56

Treatment

Primary radical cystectomy in T4b bladder cancer

is nota curative option.

If there are symptoms, radical cystectomy

may be a therapeutic/palliative option.

The indication for performing a palliative cystectomyis symptom relief

(pain, recurrent bleeding, urgency and fistula formation).

Intestinal or non-intestinal forms of urinary diversion

can be used with or without palliativecystectomy.


56/56

Documents

Bladder CancerURO