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Bladder Cancer. 2nd Clinic of Urology Medical University of Lodz. Adam Madej M.D. Marek Lipiński M.D. Ph.D. Associated Professor of Urology. EBM. Guidelineses.

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Bladder cancer

Bladder Cancer

2nd Clinic of Urology Medical University of Lodz

Adam Madej M.D.

Marek Lipiński M.D. Ph.D.

Associated Professor of Urology



Guidelineses

Guidelineses

Two guidelineses = Two diseases


Epidemiology

Epidemiology

  • fourth most common cancer in men

  • male-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


Epidemiology1

Epidemiology

Initial diagnosis of bladder cancer:

70% non-muscle-invasive

30% muscle-invasive


Risk factors

Risk factors

Tobacco smoking !!!

the most well-established risk factor

causing about 50-65% of male cases and 20-30% of female cases

related 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


Risk factors1

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 carcinoma

schistosomiasis

Cyclophosphamide

Gender


Classification

Classification

2002 TNM by UICC (Union International Contre le Cancer)


Classification1

Classification

2002 TNM by UICC (Union International Contre le Cancer)




Punlmp

PUNLMP

The PUNLMP are defined

as lesions that do not have cytological features of malignancy but show

normal urothelial cells in a papillary configuration. Although they have a negligible risk for progression, they

are not completely benign and still have a tendency to recur.


Morphological subtypes

Morphological subtypes

Muscle-invasive bladder cancer

In this stage all cases are high-grade urothelial 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


Diagnosis

Diagnosis

Symptoms

  • Painless haematuria !!!

  • urgency

  • dysuria

  • increased frequency

  • pelvic pain

  • in more advanced tumours


Diagnosis1

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.


Diagnosis2

Diagnosis

Imaging

  • IVU intravenous urography

  • CT computed tomography

  • US ultrasonography

  • CT urography


Diagnosis3

Diagnosis

Imaging

  • IVU intravenous urography

  • CT computed tomography

  • US ultrasonography

  • CT urography


Diagnosis4

Diagnosis

Imaging

  • IVU intravenous urography

  • CT computed tomography

  • US ultrasonography

  • CT urography


Diagnosis5

Diagnosis

Imaging

  • IVU intravenous urography

  • CT computed tomography

  • US ultrasonography

  • CT urography


Diagnosis6

Diagnosis

Urinary cytology

Examination of a voided urine

or

bladder-washing specimen

>>>

exfoliated cancer cells

high sensitivity

in high-grade tumours


Diagnosis7

Diagnosis

Cystoscopy

The diagnosis of bladder cancer depends on

cystoscopic examination

of the bladder

and

histological evaluation

of the resected tissue.


Diagnosis8

Diagnosis

Transurethral resection (TUR)

The goal of TUR is to make the correct diagnosis,

which means including bladder muscle in the resection biopsies.


Diagnosis9

Diagnosis

Transurethral resection (TUR)

  • 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


Diagnosis10

Diagnosis

Transurethral resection (TUR)

As a standard procedure, 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 situ

are difficult to be identified under routine cystoscopic procedures.

Small papillary tumors can be easily overlooked

during conventional white light cystoscopy.


P hotodynamic diagnosis

Photodynamic diagnosis

Photodynamic diagnisis (PDD) involves fluorescence to localise abnormal tissue. This method is based on selective accumulation of fluorochrome (hexaminolevulinate; 5-ALA) in malignant cells.

FLUOROCHROME hexaminolevulinate

5-ALA >>> PROTOPORPHYRIN IX

Optical filter (405 nm)


P hotodynamic diagnosis1

Photodynamic diagnosis

white light cystoscopy

fluorescence-guidedcystoscopy


Diagnosis11

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.


Diagnosis12

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 specimen

  • contained no muscle tissue

  • when a high-grade, non-muscle-invasive

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


Diagnosis13

Diagnosis

Imaging for staging in verified bladder tumours

Imaging is indicated only if there is a clinical consequence.

The purpose of imaging for staging invasive bladder cancer is to:

• Assess the extent of local tumour invasion

• Detect tumour spread to lymph nodes

• Detect tumour spread to other distant organs

(liver, lung, bones, peritoneum, pleura, kidney, adrenal gland and others)

Methods: CT, MR, MDCT (multidetector-row CT)


Prognostic factors for nmibc

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


Prognostic factors for nmibc1

Prognostic factors for NMIBC

Weighting

used to calculate

recurrence

and

progression

scores


Prognostic factors for nmibc2

Prognostic factors for NMIBC

Probability of recurrence and progression according to total score


Treatment

Treatment

Treatment of NMIBC


Treatment1

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 tumors

are upgraded to muscle-invasive disease.

Electrocautery or laser fulguration of the bladder tumor

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


Treatment2

Treatment

Radical cystectomy in NMIBC

High-grade T1 tumors that recur despite BCG

have 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.


Treatment3

Intravesical BCG immunotherapy

(Bacillus Calmette-Guérin immunotherapy)

Treatment

  • BCG immunotherapy is used in the treatment of Ta, T1, and CIS urothelial carcinoma of the bladder

  • decrease the rate of recurrence and progression

  • it is the most effective intravesical therapy

  • Mechanism: Immune response against BCG surface antigens

  • cross-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.


Treatment4

Treatment

Intravesical chemotherapy

Valrubicin has recently been approved as intravesical chemotherapy for CIS that is 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.


Treatment5

Treatment

Treatment of muscle-invasive and metastatic

bladder cancer


Treatment6

Treatment

The standard treatment

for patients with muscle-invasive bladder cancer

is 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.


N eoadjuvant chemotherapy

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 not recommended

in patients with PS > 2 and impaired renal function


Ecog who zubrod score

ECGO score quantify cancer patients' general well-being

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 during the day

(Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)

3 - 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


Radical cystectomy

Radical cystectomy

Indications

  • 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


Radical cystectomy1

Radical cystectomy

Indications

  • Salvage cystectomy is 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


Radical cystectomy2

Radical cystectomy

Technique

Radical cystectomy includes the removal of the

bladder

prostate

seminal vesicles

uterusadnexa

lymphadenectomy

(removal of the obturator, internal, external,

common iliac, presacral nodes and nodes at the aortic bifurcation)

The inclusion of the entire prostate in male patients,

and the extent of urethrectomy and vaginal resection in female patients, has recently been questioned.


Radical cystectomy3

Radical cystectomy

Laparoscopic cystectomy

Laparoscopic cystectomy has been shown to be feasible

both in male and female patients.

The cystectomy itself and the subsequent urinary diversion

can be done hand-assisted,

robot-assisted or unaided.


Urinary diversion

Urinary Diversion

From an anatomical standpoint three alternatives

are presently used after cystectomy:

• abdominal diversion such as ureterocutaneostomy, ileal or colonic conduit, and various forms of acutaneous continent pouch

• urethral diversion which includes various forms of gastrointestinal pouches attached to the urethra as a continent, orthotopic urinary diversion (neobladder, orthotopic bladder substitution)

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


Urinary diversion1

Urinary Diversion

Ureterocutaneostomy


Urinary diversion2

Continent cutaneous urinary diversion

Urinary Diversion

Ileal conduit



Urinary diversion3

Orthotopic neobladder

Ureterocolonic diversion

Urinary Diversion





Treatment7

Treatment

Treatment of non-rescetable tumors


Treatment8

Treatment

Primary radical cystectomy in T4b bladder cancer

is not a curative option.

If there are symptoms, radical cystectomy

may be a therapeutic/palliative option.

The indication for performing a palliative cystectomy is symptom relief (pain, recurrent bleeding, urgency and fistula formation).

Intestinal or non-intestinal forms of urinary diversion

can be used with or without palliativecystectomy.


Bladder cancer1

Bladder Cancer

2nd Clinic of Urology Medical University of Lodz

Thank you


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