Bladder Cancer

Adam Madej M.D.

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

2nd

Clinic

of U

rolo

gy

Med

ical

Unive

rsity

of L

odz

EBM

Guidelineses

Two guidelineses = Two diseases

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

Epidemiology

Initial diagnosis of bladder cancer:

70% non-muscle-invasive30% muscle-invasive

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 chemicalswork-related cases = 20-25%

benzene derivatives and arylaminesProfessions who use rubbers, textiles, paints, leathers and chemicals

Phenacetin

Risk factors

EBRT external beam radiation therapy for gynaecological malignancies

Dietary factorshypothesis; vegetable and fruit intake

reduced the risk of bladder cancer

Chronic urinary tract infectioninvasive squamous cell carcinoma

schistosomiasis

Cyclophosphamide

Gender

Classification

2002 TNM by UICC (Union International Contre le Cancer)

Classification

2002 TNM by UICC (Union International Contre le Cancer)

NMIBC

Histological grading

PUNLMP

The PUNLMP are defined as lesions that do not have cytological features of malignancy but

shownormal 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

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

Symptoms

• Painless haematuria !!!

• urgency• dysuria

• increased frequency• pelvic pain

in more advanced tumours

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 outbefore and after TUR to assess

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

Diagnosis

Imaging

• IVU intravenous urography

• CT computed tomography

• US ultrasonography

• CT urography

Diagnosis

Imaging

• IVU intravenous urography

• CT computed tomography

• US ultrasonography

• CT urography

Diagnosis

Imaging

• IVU intravenous urography

• CT computed tomography

• US ultrasonography

• CT urography

Diagnosis

Imaging

• IVU intravenous urography

• CT computed tomography

• US ultrasonography

• CT urography

Diagnosis

Urinary cytology

Examination of a voided urineor

bladder-washing specimen>>>

exfoliated cancer cells

high sensitivityin high-grade tumours

Diagnosis

Cystoscopy

The diagnosis of bladder cancer depends on

cystoscopic examination of the bladder

and histological evaluation of the resected tissue.

Diagnosis

Transurethral resection (TUR)

The goal of TUR is to make the correct diagnosis, which means including bladder muscle in the resection biopsies.

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 detrusor muscle

• edges of the resection area

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.

Photodynamic diagnosis

FLUOROCHROME hexaminolevulinate

5-ALA >>> PROTOPORPHYRIN IX

Optical 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.

Photodynamic diagnosis

white light cystoscopy fluorescence-guided cystoscopy

Diagnosis

Bladder and prostatic urethral biopsy

The biopsies from normal-looking mucosa in patients with bladder tumoursso called random biopsies (R-biopsies)

or selected site mucosal biopsiesare only recommended if fluorescent areas are seen

with photodynamic diagnosis (PDD).

Cold cup biopsies from normal-looking mucosa should be performedwhen cytology is positive,

when exophytic tumour is of non-papillary appearance, or when fluorescent areasare seen with PDD.

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

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

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 NMIBC

Weighting used to calculate

recurrence and

progression scores

Prognostic factors for NMIBC

Probability of recurrence and progression according to total score

Treatment

Treatment of

NMIBC

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.

Treatment

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.

Radical cystectomy in NMIBC

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.

Intravesical BCG immunotherapy (Bacillus Calmette-Guérin immunotherapy)

Treatment

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.

Intravesical chemotherapy

Treatment

Treatment of muscle-invasive and metastatic

bladder cancer

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.

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

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

ECGO score quantify cancer patients' general well-being

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

Radical cystectomy

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

Indications

Radical cystectomy

Radical cystectomy includes the removal of the bladder

prostate seminal vesicles

uterus adnexalymphadenectomy

(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.

Technique

Radical 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.

Laparoscopic cystectomy

Urinary Diversion

• 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.

From an anatomical standpoint three alternatives are presently used after cystectomy:

Urinary Diversion

Ureterocutaneostomy

Urinary Diversion

Ileal conduit

Continent cutaneous urinary diversion

Colon conduit

Urinary Diversion

Ureterocolonic diversion

Orthotopic neobladder

VESICA ILEALE PADOVANA (VIP)

Urinary Diversion

Radical cystectomy

Treatment

Treatment of non-

rescetable tumors

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 Cancer

Thank you

2nd

Clinic

of U

rolo

gy

Med

ical

Unive

rsity

of L

odz