Bladder Cancer
Adam Madej M.D.
Marek Lipiński M.D. Ph.D.
Associated Professor of Urology
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-invasive
30% muscle-invasive
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 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
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 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
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 out
before 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 urine
or
bladder-washing specimen
>>>
exfoliated cancer cells
high sensitivity
in 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
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)
Photodynamic diagnosis
white light cystoscopy
fluorescence-guided cystoscopy
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.
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
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
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.
Treatment
Intravesical BCG immunotherapy
(Bacillus Calmette-Guérin immunotherapy)
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.
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.
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
ECGO score quantify cancer patients' general well-being
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
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 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 cystectomy
Technique
Radical cystectomy includes the removal of the
bladder
prostate
seminal vesicles
uterus adnexa
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 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
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 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