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