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PRESENTED BY: DR. VIKAS KUMAR
MODERATOR : DR.P.K.PURI
(HOD DEPTT. OF UROLOGY,IGMC,
SHIMLA)
INTRODUTION
•Bladder cancer is the 9th most common cancer overall and 2nd
after
prostate ca in genitourinary sys.
Bladder cancer is the 13th most common cause of death worldwide
Sixty-three percent of all bladder cancer cases occur in developed
countries, with 55% from North America and Europe
In North America and Europe, 95% to 97% of cases are urothelial
carcinoma;
 in Africa 60% to 90% are urothelial and 10% to 40% are
squamous cell; and
Egypt has the highest rate of squamous cell carcinoma because of
the endemic infections with Schistosoma species .
 Bladder cancer is 3 times more common in men than in
women.
 Bladder cancer is rare in persons less than the age of 40
years and typically nonaggressive and well differentiated
 The median age of bladder cancer diagnosis is 65 years of
age for men and women, and the incidence and mortality
from the disease increases with age.
 The incidence rate of bladder cancer is decreasing faster in
men than in women because of the recent decrease in the
percent of men smoking compared with women.
ETIOLOGY
I) GENETIC
- The null GSTM1 polymorphism is
associated with an increased bladder risk with
a relative risk of 1.5.
- The slow NAT-2 polymorphism is
related to bladder cancer with an odds ratio of
1.4 compared with the fast polymorphism
II) EXTERNAL RISK FACTORS
i) Smoking – 60-70%
ii) Aromatic amines – 20-27%
iii) Nutritional Factors - fruits and vegetables
protective; salted and barbequed meat, pork, total fat,
pickled vegetables, soy, and spices procarcinogenic
iv) Inflammation/Infection -
Schistosoma hematobium, human papillomavirus,
Escherichia coli,Pseudomonas,and gonorrhea
v) Radiation
vi) Chemotherapy
vii) Heredity
PATHOLOGY
 Histologically, 90% of bladder cancers are of urothelial origin, 5%
are squamous cell carcinomas, and less than 2% are
adenocarcinoma or other variants.
 At initial presentation, 80% of urothelial tumors are non–muscle
invasive.
 There are multiple growth patterns of urothelial cancer, including
flat carcinoma in situ (CIS), papillary tumors that can be low or
high grade, and sessile tumors with a solid growth pattern
WHO Classification of Noninvasive and
Invasive Urothelial Neoplasia
 Noninvasive Urothelial Neoplasia
 Hyperplasia (flat and papillary)
 Reactive atypia
 Atypia of unknown significance
 Urothelial dysplasia (low-grade intraurothelial neoplasia)
 Urothelial carcinoma in situ (high-grade intraurothelial
neoplasia)
 Urothelial papilloma
 Urothelial papilloma, inverted type
 Papillary urothelial neoplasm of low malignant potential
 Noninvasive low-grade papillary urothelial carcinoma
 Noninvasive high-grade papillary urothelial carcinoma
 Invasive Urothelial Neoplasia
 Lamina propria invasion
 Muscularis propria (detrusor muscle) invasion
STAGING
PRIMARY TUMOR (T)
 TX Primary tumor cannot be assessed
 T0 No evidence of primary tumor
 Ta Noninvasive papillary carcinoma
 Tis Carcinoma in situ: “flat tumor”
 T1 Tumor invades subepithelial connective tissue
 T2 Tumor invades muscularis propria
pT2a Tumor invades superficial muscularis propria (inner half)
pT2b Tumor invades deep muscularis propria (outer half)
 T3 Tumor invades perivesical tissue:
pT3a Microscopically
pT3b Macroscopically (extravesical mass)
 T4 Tumor invades any of the following: prostatic stroma, seminal
vesicles, uterus, vagina, pelvic wall, abdominal wall
 T4a Tumor invades prostatic stroma, uterus, vagina
 T4b Tumor invades pelvic wall, abdominal wall
REGIONAL LYMPH NODES (N)
 NX Lymph nodes cannot be assessed
 N0 No lymph node metastasis
 N1 Single regional lymph node metastasis in the
true pelvis (hypogastric, obturator, external
iliac, or presacral lymph node)
 N2 Multiple regional lymph node metastasis in
the true pelvis (hypogastric, obturator,
external iliac, or presacral lymph node metastasis)
 N3 Lymph node metastasis to the common iliac lymph
nodes
Distant Metastasis (M)
 M0 No distant metastasis

M1 Distant metastasis
Anatomic Stage
Group T N M
 Stage 0a Ta N0 M0
 Stage 0is Tis N0 M0
 Stage I T1 N0 M0
 Stage II T2a N0 M0
T2b N0 M0
 Stage III T3a N0 M0
T3b N0 M0
T4a N0 M0
 Stage IV T4b N0 M0
Any T N1-3 M0
Any T Any N M1
DISSEMINATION
A) Angiolymphatic Invasion : seen in approximately 25% of invasive
urothelial carcinoma.
B) Pagetoid Spread : Pagetoid spread occurs when cancer cells grow
underneath a layer of normal-appearing surface urothelium.
-Pagetoid spread of urothelial cancer can occur into the prostatic
urethra and distal ureters.
-Biopsies of normal-appearing prostatic urothelium are needed
in the evaluation of patients with positive urine cytology and yet
endoscopically normal bladder
C) Direct Extension : Direct extension of tumors into the basal lamina,
connective tissue, and, ultimately, the angiolymphatic system is
caused by genetic and epigenetic changes.
DETECTION OF UROTHELIAL
CARCINOMA
 Gross, painless hematuria is the primary
symptom in 85% of patients
 Fifty percent of patients with gross hematuria will
have a demonstrable cause, 20% will have a
urologic malignancy, and 12% will have a bladder
tumor
 The AUA guidelines for microscopic hematuria
evaluation include a cystoscopy, upper tract
imaging, and urine cytology
INVESTIGATIONS
1) URINE CYTOLOGY
-Positive urine cytology is virtually
diagnostic of a bladder tumor
-the gold standard urinary marker
against which other markers are held
- the sensitivity and specificity for
cytology in detecting bladder cancer is 40% to
62% and 94% to 100%, respectively.
1) 2) CYSTOSCOPY
A) White light cystoscopy (WLC) is the gold standard.
- White light cystoscopy has an excellent sensitivity of 87% and
specificity of 85% for papillary tumors but is relatively poor for CIS
(15%).
B) Blue light cystoscopy : Porphyrin-induced fluorescence
cystoscopy uses photoactive porphyrins, such as hexaminolevulinate,
that accumulate preferentially in neoplastic tissue and emit red
fluorescence under blue-wavelength light.
-This may improve the detection of small papillary lesions and CIS.
- Blue light cystoscopy detected 58% of CIS ; and sensitivity of 87%
CARCINOMA URINARY BLADDER
C) Narrow-band imaging (NBI) is an endoscopic optical image
enhancement technique that enhances the contrast between mucosal
surfaces and microvascular structures without the use of dyes.
- vascular structures appear dark brown or green against a pink
or white mucosal background.
- sens. 100% and sp.82%
-NBI more accurately detects tumor recurrence after BCG
therapy than do urine cytology or white light cystoscopy,
3) RANDOM BLADDER BIOPSY
-Random bladder biopsies are
recommended to detect unsuspected CIS or small
papillary tumors in endoscopically normal urothelium.
- Overall, there is a 2.5% detection rate of
CIS or small papillary tumors in random biopsies of
patients with known or suspected bladder tumors.
-It is reasonable to perform random
biopsies in high-risk individuals, such as for those given
postintravesical therapy or for those with a positive
cytology and an endoscopically negative bladder.
4) URINE MARKERS
-There are various urine markers that evaluate
secreted proteins or shed cells in the hope of noninvasively
detecting bladder cancer.
-To date, none of these markers have a high
enough sensitivity or specificity to replace office cystoscopy.
MARKER MEDIAN SENSITIVITY (%) MEDIAN SPECIFICITY (%)
 BTA stat 70 75
 BTAtrak 69 65
 NMP22 73 80
 FDP 61 79
 ImmunoCyt 83 80
 Cytometry 60 80
 Quanticyt 59 79
 Hb-dipstick 52 82
 Lewis X 83 85
 FISH 84 95
 Telomerase 75 86
 Microsatellite 91 94
 CYFRA21-1 94 86
 UBC 78 91
 Cytokeratin 20 91 84
 BTA 50 86
 TPS 72 78
NON–MUSCLE-INVASIVE BLADDER
CANCER
 DEF : malignant urothelial tumors that have not
invaded the detrusor are more appropriately
termed non–muscle invasive traditionally known
as superficial bladder cancer .
 Approximately 70% are non–muscle invasive at
presentation. Of these, 70% present as stage Ta,
20% as T1, and 10% as CIS
 Stage Ta tumors are usually low grade. Although
recurrence is common, especially in the setting of
multiplicity, progression is rare .
 Between 40% and 83% of patients with CIS will
develop muscle invasion if untreated.
 T1 tumors are usually papillary. Deep penetration
into the lamina propria, especially if involving
muscularis mucosae, increases the risk of
recurrence and progression
Non-Muscle Invasive Bladder CancerNon-Muscle Invasive Bladder Cancer
Carcinoma in SituCarcinoma in Situ
 There is significant potential for
understaging in patients with high-grade,
apparently non–muscle-invasive tumors,
especially for those that appear to be
stage T1.
 one third of patients believed to have
non–muscle-invasive disease at the time
of cystectomy were found to actually have
muscle invasion, only half of which were
organ confined. Metastases were already
present in 8% of these patients.
NMIUCNMIUC PrognosisPrognosis correlates with:correlates with:
 Tumor gradeTumor grade
 +/- CIS+/- CIS
 Tumor SizeTumor Size
 MultiplicityMultiplicity
 Papillary vs SessilePapillary vs Sessile
 +/- Lymphovascular Invasion+/- Lymphovascular Invasion
ENDOSCOPIC SURGICAL
MANAGEMENT
 TUR of bladder tumor (TURBT)
under regional or general
anesthesia is the initial treatment
for visible lesions and is performed
to
(1) remove all visible tumors
and
(2) provide specimens for
pathologic examination to
determine stage and grade.
 Bimanual examination of the
bladder should be performed
under anesthesia before
prepping and draping unless the
tumor is clearly small and
noninvasive, and it should be
repeated after resection.
 Fixation or persistence of a palpable mass after resection
suggests locally advanced disease.
 Friable, low-grade tumors can often be removed without the use
of electrical energy
 If a tumor appears to be muscle invasive, biopsies of the borders
and base in order to establish invasion may be performed in lieu
of complete resection, because cystectomy will likely follow based
on confirmatory biopsies
 Consensus is that patients with pT1 and high-grade Ta tumors
merit repeat resection after 2 to 3 weeks
A, Broad-based papillary lesion. B, Resection of lesion with loop
electrocautery. C, Depth of resection to detrusor muscle.
Complications of Transurethral
Resection of Bladder Tumor
- Minor bleeding
- irritative symptoms
- uncontrolled hematuria
- clinical bladder perforation
-TUR Syndrome
--UO Obstruction
Why Do Patients Recur?
 Nature of the tumor…
 Missed tumors at TURBT
 Incomplete TURBT resection
 Implantation of shed tumor cells at
TURBT
Perioperative Intravesical Therapy to Prevent
Tumor Implantation
 It is believed that tumor cell implantation
immediately after resection is responsible for
many early recurrences and this has been used to
explain the observation that initial tumors are
most commonly found on the floor and lower side
walls of the bladder, whereas recurrences are
often located near the dome.
 Thus intravesical chemotherapy to kill such cells
before implantation has been used
 Mitomycin C (MMC) appears to be the most effective
adjuvant intravesical chemotherapeutic agent
perioperatively.
 a single dose administered within 6 hours lessens
recurrence rates, whereas a dose 24 hours later does not
 Recurrence dropped from 48.4% to 36.7%
 Destroys residual microscopic tumor at the TURBT site
 Used to prevent tumor implantation
 Perforation is absolute contraindication
IMMUNOTHERAPYIMMUNOTHERAPY
 Goal of immunotherapy is to
 Augment cancer cell recognition
 Promote tumor cell-specific cytotoxicity
 Recruit tumor cells that have evaded the immune system
“onto the radar”
 Intravesical immunotherapy results in a massive local
immune response characterized by induced expression
of cytokines in the urine and bladder wall and by an
influx of granulocytes, mononuclear, and dendritic cells
1) Bacillus Calmette-Guérin
- BCG is an attenuated mycobacterium
developed as a vaccine for tuberculosis that has
demonstrated antitumor activity in several different
cancers including UC
-BCG is stored in refrigeration and
reconstituted from a lyophilized powder.
 Use in CIS
 CIS is often diffuse preventing complete tumor
resection
 80% response rate
 50% durable at 4 yrs and 30% at 10 yrs
 Higher efficacy compared with intravesical
chemo
 Use in residual tumor
 Effectively treats Ta papillary lesions, but not a surgical
substitute
 TURP + delayed BCG to prostatic urethra is effective treatment
for prostatic CIS
 Use as prophylaxis for 6 weeks after TURBT
 Induction decreased recurrence by up to 40% for T1 lesions
compared to TUR alone
 Induction + Maintenance can reduce progression by 20-30% in
HG tumors
 Maintenance is thought to provide long-term
immunostimulation
BCG SCHEDULING
-Treatments are generally begun 2 to
4 weeks after tumor resection, allowing time for
re-epithelialization, which minimizes the potential
for intravasation of live bacteria
-The vaccine (80-120 mg) is
reconstituted with 50 mL of saline and should be
administered through a urethral catheter under
gravity
-In the event of a traumatic
catheterization, the treatment should be delayed
for several days to 1 week, depending on the
extent of injury.
 After instillation, the patient should retain the
solution for at least 2 hours
 Patient should turn from side to side to bathe the
entire urothelium
 Fluid, diuretic, and caffeine restriction before
instillation is essential to limit dilution of the
agent with urine and to facilitate retention of the
agent for 2 hours
 6 week induction alone is insufficient to achieve optimal
response
 Lamm and SWOG Maintenance
– (after 6 week induction)
 @ 3 months- 3 weekly instillations
 @ 6 months- 3 weekly instillations
 then every 6 months for 3 yrs
 Quinolones may affect the viability of BCG and
should be avoided if possible during the course of
BCG treatments
CONTRAINDICATIONS
 Absolute Contraindications
 Immunosuppressed and
immunocompromised patients
 Immediately after transurethral resection
on the basis of the risk of intravasation
and septic death
 Personal history of BCG sepsis
 Gross hematuria (intravasation risk)
 Traumatic catheterization (intravasation
risk)
 Total incontinence (patient will not retain
agent)
 Relative Contraindications
 Urinary tract infection (intravasation risk)
 Liver disease (precludes treatment with
isoniazid if sepsis occurs)
 Personal history of tuberculosis (risk theorized
but unknown)
 Poor overall performance status
 Advanced age
 No or Insufficient Data on Potential Need
for Contraindications
 Patients with prosthetic materials
 Ureteral reflux
 Anti–tumor necrosis factor medications
(theoretically predispose to BCG sepsis)
SIDE EFFECTS
Grade 1: Moderate Symptoms <48 Hr
 Mild/moderate irritative voiding symptoms, mild hematuria, fever
<38.5° C
 ASSESSMENT
 Possible urine culture to rule out bacterial urinary tract infection
 SYMPTOM MANAGEMENT
 Anticholinergics, analgesics, nonsteroidal anti-inflammatory drugs
Grade 2: Severe Symptoms and/or >48 Hr
Severe irritative voiding symptoms, hematuria, or symptoms lasting
>48 hr
All maneuvers for grade 1, plus the following:
ASSESSMENT
Urine culture, chest radiograph, liver function tests
MANAGEMENT
Consult immediately with physician experienced in
management of mycobacterial infections/complications.
Consider dose reduction to one half to one third of dose
when instillations resume.
Treat culture results as appropriate.
 ANTIMICROBIAL AGENTS
 Administer isoniazid and rifampins, 300 mg/day and 600 mg/day,
orally until symptom resolution.
 Do not use monotherapy.
 Observe for rifampin drug-drug interactions (e.g., warfarin).
Grade 3: Serious Complications (Hemodynamic Changes,
Persistent High-Grade Fever)
 ALLERGIC REACTIONS (JOINT PAIN, RASH)
 Perform all maneuvers described for grades 1 and 2, plus the
following:
 Isoniazid, 300 mg/day, and rifampin, 600 mg/day, for 3-6
months depending on response
SOLID ORGAN INVOLVEMENT (EPIDIDYMITIS, LIVER, LUNG, KIDNEY,
OSTEOMYELITIS, PROSTATE)
• Isoniazid, 300 mg/day, rifampin, 600 mg/day, ethambutol, 15
mg/kg/ day single daily dose for 3-6 months
•Cycloserine often causes severe psychiatric symptoms and is to be
strongly discouraged.
•BCG is almost uniformly resistant to pyrazinamide, so this drug has
no role.
•Consider prednisone, 40 mg/day, when response is inadequate or
for septic shock (never given without effective antibacterial therapy).
2) INTERFERON
-Interferons have multiple antitumor activities
* inhibition of nucleotide synthesis;
*upregulation of tumor antigens,
*antiangiogenic properties; and
*stimulation of cytokine release with enhanced T and B cell
activation, as well as enhanced natural killer cell activity.
-Interferon as a solitary agent is more expensive
and less effective than BCG or intravesical chemotherapy in
eradicating residual disease, preventing recurrence of papillary
disease, and treating CIS
-Combination of BCG and interferon is superior
3) NEWER IMMUNOTHERAPEUTIC AGENTS
 Keyhole-limpet hemocyanin (KLH) from the
hemolymph of the mollusk Megathura crenulata
 Bropirimine
 Mycobacterial cell wall DNA extract
 Thiosulfinate extracts of garlic
 Interleukin-12
INTRAVESICAL CHEMOTHERAPY
 INDICATIONS
 Low grade tumor
 Multifocal tumor
 Recurrences > 4
 CIS
 Intravesical chemotherapy has a clear impact on tumor
recurrence when immediately instilled after TURBT and in
the adjuvant setting.
 There is no clear evidence of an impact on progression.
 Combinations of various chemotherapeutic agents and
chemotherapy combined with BCG have not demonstrated
major benefit combined with single-agent treatment, with
the exception of interferon
 Given for 6-8 wks post op. but response not better than
BCG
 Various chemotherapeutic agents
include:
 Mitomycin C
 Doxorubicin and Its Derivatives
 Thiotepa
 Gemcitabine and
 Taxanes
EARLY CYSTECTOMY
• Should be considered in patients
-Micropapillary Variant
– Do not tolerate intravesical therapy
– Failed attempts at disease control with TURBT +IVT
– Lesions not amenable to endoscopic resection
– Failure of TURBT and intravesical therapy
• Recurrence at higher grade and multifocality
• Progression on intravesical therapy (Grade Progression)
• Invasion into detrusor (T progression)
• Especially in HGTa or CIS
RADIATION THERAPY
• Has not been studied extensively in NMI
Urothelial Ca
• Initial very good response, short term
• Not effective long term for Ta or CIS
– 90% recur in 5 years
AMERICAN UROLOGICAL ASSOCIATION 2007
GUIDELINES FOR NON–MUSCLE-INVASIVE BLADDER
CANCER
 Index Patient #1: Abnormal Urothelial “Growth”
but Not Proven Cancer
 Standard: Obtain biopsy to confirm grade
for all index patients
 If possible, eradicate all visible tumors
 If cancer, periodic cystoscopy
 Option: Single dose of postoperative
intravesical chemotherapy
 Index Patient #2: Small-Volume, Low-Grade
Ta
Recommendation: Single dose of postoperative
intravesical chemotherapy
 Index Patient #3: Multifocal or Large Low-
Grade Ta, or Recurrent Low-Grade Ta
 Recommendation: Intravesical BCG or MMC—
goal to prevent/delay recurrence
 Option: Maintenance BCG or MMC
 Index Patient #4: High-Grade Ta, T1, or CIS
 Standard: If T1 disease, but no muscularis in specimen,
repeat resection
 Recommendation: Intravesical BCG with maintenance
therapy
 Option: Consider cystectomy for select patients
 Index Patient #5: High-Grade Ta, T1, and/or CIS
Following Prior Intravesical Therapy
 Standard: T1 disease but no muscularis in
specimen, repeat resection
 Recommendation: Consider cystectomy as
therapeutic alternative
 Option: Further intravesical therapy may be
considered
INVASIVE BLADDER CANCER
DEF. : It includes T2 and beyond bladder cancer
 The majority (80%) of patients with bladder cancer present de
novo with muscle-invasive disease as its first manifestation.
 The remaining 15% to 20% progress from non–muscle-invasive
cancer after treatment with intravesical therapy.
 Deaths due to bladder cancer invariably occur as a result of
distant metastases present at the time of loco-regional therapy.
 Progression of cancer after definitive loco-regional therapy
commonly occurs within the first 2 years after treatment
STAGING AND EVALUATION
 Laboratory testing at a minimum
should include
 complete hemogram,
 blood urea,
 creatinine,
 electrolytes,
 liver function tests
 IMAGING STUDIES:
 CXR
 CT Abd & pelvis
 CT Chest
 Bone scan
 MRI
 PET
 Tumor markers- CEA,CA19.9,CA 125
MANAGEMENT
 I) SURGICAL
 II) NEOADJUVANT CHEMOTHERAPY
 III)ADJUVANT CHEMOTHERAPY
SURGICAL
 I) RADICAL CYTECTOMY
 II) BLADDER PRESERVATION
SURGERY
Indications for radical cystectomy
 Infiltrating muscle-invasive bladder cancer without
evidence of metastasis or with low-volume, resectable
locoregional metastases (stage T2-T3b)
 Superficial bladder tumors characterized by any of the
following:
 Refractory to cystoscopic resection and intravesical
chemotherapy or immunotherapy
 Extensive disease not amenable to cystoscopic
resection
 Invasive prostatic urethral involvement
 Primary adenocarcinoma, SCC, or sarcoma
 Stage-pT1, grade-3 tumors unresponsive to intravesical
BCG vaccine therapy
 CIS refractory to intravesical immunotherapy or
chemotherapy
 Palliation for pain, bleeding, or urinary frequency
RADICAL CYSTECTOMY
 Radical Cystectomy
 Removal of bladder with surrounding fat
 Prostate/seminal vesicles (males)
 Uterus/cervix/fallopian tubes/ovaries /ant. Vault of vagina
(females)
 + Urethrectomy
 Pelvic Lymphadenectomy
 More is better
 Urinary Diversion
 Conduit urinary diversion
 Continent cutaneous reservoir
 Orthotopic neobladder
Radical Cystectomy
 Midline incision
 Thorough intraabdominal exploration (rule out
metastatic disease)
 Assess resectability of bladder
Step 1: mobilize the urachus from the umbilicus
Step 2: mobilize the bladder from the bowel
Step 3: isolate and transect ureters
Step 4: complete lymph node dissection
Step 5: separate bladder from sigmoid colon
Step 6: complete posterior dissection and cut off bladder blood supply
Step 7: complete anterior dissection and isolate urethra
Step 8: transect urethra and remove specimen
Cystectomy is not performed when
(1)lymph node metastases are unresectable because of
bulk or proximal extent above the common iliac
vessels;
(2) there is evidence of extensive periureteral disease;
(3) the bladder is fixed to the pelvic sidewall; or
(4) tumor is invading the rectosigmoid colon.
PELVIC LYMPHADENECTOMY
 ~25% have LN involvement at cystectomy
 25 nodes be the minimum number to be
removed
 Accurate staging
 Assessment of prognosis
 Adjuvant therapies (chemotherapy, clinical trials)
 Therapeutic benefit
 Removal of micrometastatic disease
Standard LNDStandard LND ExtendedExtended
LND
Pelvic Lymphadenectomy
Urinary Diversion
 Use of intestinal segment to bypass/ reconstruct/
replace the normal urinary tract
 Goals:
 Storage of urine without absorption
 Maintain low pressure even at high volumes to allow
unobstructed flow of urine from kidneys
 Prevent reflux of urine back to the kidneys
 Socially-acceptable continence
 Empties completely
 “Ideal” diversion has yet to be discovered
Types of Urinary Diversion
ILEAL CONDUIT
(incontinent
diversion to
skin)
CONTINENT
CUTANEOUS
RESERVOIR
(continent
diversion to
skin)
ORTHOTOPIC
NEOBLADDER
(continent
diversion to
urethra)
Figures from www.clevelandclinic.org/health/health-info/docs
Ileal Conduit
 15-20 cm of small
intestine (ileum) is
separated from the
intestinal tract
 Intestines are sewn
back together (re-
establish intestinal
continuity)
Ileal Conduit
 Ureters are attached to
one end of the segment
of ileum
 Natural peristalsis of
intestine propels urine
through the segment
 Other end is brought
out through an opening
on the abdomen
ureter
ureter
Ileum
Ileal Conduit
ADVANTAGES
 Simplest to perform
 Least potential for
complications
 No need for intermittent
catheterization
 Less absorption of urine
DISADVANTAGES
 Need to wear an external
collection bag
 Stoma complications
 Parastomal hernia
 Stomal stenosis
 Long-term sequelae
 Pyelonephritis
 Renal deterioration
Continent Cutaneous Reservoir
 Many variations (same theme)
 Indiana Pouch, Penn Pouch, Kock Pouch…
 All use various parts of the intestine
 ileum, right colon most commonly
 Reservoir
 “Detubularized” intestine- low pressure storage
 Continence mechanism
 Ileocecal valve (Indiana)
 Flap valve (Penn, Lahey)
 Intussuscepted nipple valve (Kock)
Continent Cutaneous Reservoir
INDIANA POUCH
Appendix
removed
Right colon
and distal
ileum
isolated
Right colon is
opened
lengthwise
and folded
down to
create a
sphere
Continent Cutaneous Reservoir
INDIANA POUCH
RESERVOIR
EFFERENT LIMB
(to skin)
catheter
Ureters attached to back of reservoir (not shown)
Continence
maintained by
ileocecal valve
Continent Cutaneous Reservoir
ADVANTAGES
 No external bag
 Stoma can be covered
with bandaid
DISADVANTAGES
 Most complex
 Need for regular
intermittent
catheterization
 Potential complications:
 Stoma stenosis
 Stones
 Urine infections
Orthotopic Neobladder
 Currently the diversion of choice
 Studer, T-Pouch, Hautmann, Ghoniem, etc.
COMPONENTS:
 Internal reservoir – detubularized ileum
 Connect to urethra (“efferent limb”)
 Urethral sphincter provides continence
 “Afferent Limb” – ureteral connection
 Antirefluxing (T-Pouch, Kock)
 Low pressure isoperistaltic limb (Studer)
Orthotopic Neobladder
15-20 cm
44 cm
Ureters
attache
d
Connect to urethra
Ileum
detubularize
d Reservoir
STUDER ILEAL NEOBLADDER
22 cm
22 cm
15-20 cm
Isolation of ileal segment
Orthotopic Neobladder
Orthotopic Neobladder
Afferent Limb
Detubularization of ileum
Orthotopic Neobladder
Afferent Limb Reservoir
Opening to
urethra
Orthotopic Neobladder
ADVANTAGES
 No external bag
 Urinate through
urethra
 May not need
catheterization
DISADVANTAGES
 Incontinence (10-
30%)
 Retention (5-20%)
 Risk of stones,
UTI’s
 Need to “train”
neobladder
Choice of Urinary Diversion
 Disease Factors
 Urethral margin
 Patient Factors
 Kidney function / liver function
 Manual dexterity
 Preoperative urinary continence/ urethral strictures
 Motivation
 Surgeon Factors
 Familiarity with various types of diversions
Urinary Diversions
 Enterostomal therapist is CRITICAL for success
 Urinary diversions require lifelong follow-up
 Imaging (kidneys/ureters/diversion)
 Labs (electrolytes, acid-base, B12 levels)
 Cancer follow-up (surveillance imaging, cytology)
BLADDER PRESERVATION
APPROACHES
1) Radical Transurethral Resection of
Bladder Tumor (TURBT)
 Criteria
a) initial occurrence of bladder cancer;
b) no CIS;
c) size less than or equal to 3 cm;
d) stage T2 (no palpable mass); and
e) not in the dome or high posterior wall because of the risk
of bowel injury
2) Partial Cystectomy
 Criteria
a) Same as for TURBT plus
b) Located at dome and away from the ureteral orifices.
Bilateral pelvic lymphadenectomy is performed at the time of
surgery for pathologic staging of the nodes
3) Trimodality Therapy
TURBT + CHEMO + RT
Criteria
a) clinical stage (organ-confined),
b) tumor size less than 3 to 5 cm,
c) absence of hydronephrosis,
d) absence of a palpable mass, and
e) unifocal disease
Role of neoadjuvant
chemotherapy
 Chemotherapy before surgery has several advantages.
 Therapy is better tolerated before surgery or radiation.
 Chemotherapy-related toxicities are considerably less in patients
with localized disease than in those with metastatic disease on
the basis of performance status.
 Patients are often able to tolerate a greater dose intensity and
more cycles of chemotherapy preoperatively than postoperatively.
 Neoadjuvant chemotherapy allows in vivo drug sensitivity testing
that may provide useful information for later therapy.
 The primary tumor can be evaluated for response, which also has
major prognostic significance.
 In addition, preoperative chemotherapy may down-stage tumors,
potentially allowing for technically easier surgery
 DISADVANTAGE
 delay in definitive local therapy in patients who do not respond or
whose disease progresses.
 An interval longer than 12 weeks between the diagnosis of muscle
invasion and cystectomy has even been associated with a poorer
outcome.
 increase in the incidence of perioperative morbidity.
ADJUVANT CHEMOTHERAPY
 In patients with pT3-4 and/or N+M0 disease, 5-year survival after
radical cystectomy is only 25% to 35% at best.
 As a result, adjuvant chemotherapy has been advocated for high-
risk patients in an effort to delay recurrence and prolong survival
 ADVANTAGES
 An adjuvant approach allows selection of patients at highest risk
of metastatic or recurrent disease on the basis of an accurate
pathologic evaluation.
 Surgery is performed without delay, and the advent of orthotopic
neobladders and continent urinary diversions has improved
quality of life in patients after cystectomy, favoring immediate
cystectomy.
 There is evidence that delaying cystectomy can be detrimental (,
and no time is wasted in those patients who do not respond to
chemotherapy.
 The availability of sufficient tissue for increasingly sophisticated
analysis of molecular prognostic and predictive markers is also a
potential advantage.
 If micrometastases are present, they can be treated with
chemotherapy when at a low volume, rather than after there is
overt metastatic disease.
 DISADVANTAGES
 bladder is not preserved and that there is a delay in
starting systemic therapy for occult metastases
while the focus is first on the primary tumor.
 Response cannot be easily evaluated, and the only
clinical end point that can be assessed is the time to
tumor recurrence
 difficulty in administering chemotherapy to those
with surgical morbidities following cystectomy.
ROBOTIC AND LAP. RADICAL
CYSTOPROSTATECTOMY
 Robotic-assisted and lap. radical
cystectomy represents an evolving field in
urology.
 It is certainly one tool that can be used in
the treatment of invasive bladder cancer.
 Morbidity is limited, operative time is
comparable, and long-term oncologic
outcomes are awaited.
CARCINOMA URINARY BLADDER

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CARCINOMA URINARY BLADDER

  • 1. PRESENTED BY: DR. VIKAS KUMAR MODERATOR : DR.P.K.PURI (HOD DEPTT. OF UROLOGY,IGMC, SHIMLA)
  • 2. INTRODUTION •Bladder cancer is the 9th most common cancer overall and 2nd after prostate ca in genitourinary sys. Bladder cancer is the 13th most common cause of death worldwide Sixty-three percent of all bladder cancer cases occur in developed countries, with 55% from North America and Europe In North America and Europe, 95% to 97% of cases are urothelial carcinoma;  in Africa 60% to 90% are urothelial and 10% to 40% are squamous cell; and Egypt has the highest rate of squamous cell carcinoma because of the endemic infections with Schistosoma species .
  • 3.  Bladder cancer is 3 times more common in men than in women.  Bladder cancer is rare in persons less than the age of 40 years and typically nonaggressive and well differentiated  The median age of bladder cancer diagnosis is 65 years of age for men and women, and the incidence and mortality from the disease increases with age.  The incidence rate of bladder cancer is decreasing faster in men than in women because of the recent decrease in the percent of men smoking compared with women.
  • 4. ETIOLOGY I) GENETIC - The null GSTM1 polymorphism is associated with an increased bladder risk with a relative risk of 1.5. - The slow NAT-2 polymorphism is related to bladder cancer with an odds ratio of 1.4 compared with the fast polymorphism
  • 5. II) EXTERNAL RISK FACTORS i) Smoking – 60-70% ii) Aromatic amines – 20-27% iii) Nutritional Factors - fruits and vegetables protective; salted and barbequed meat, pork, total fat, pickled vegetables, soy, and spices procarcinogenic
  • 6. iv) Inflammation/Infection - Schistosoma hematobium, human papillomavirus, Escherichia coli,Pseudomonas,and gonorrhea v) Radiation vi) Chemotherapy vii) Heredity
  • 7. PATHOLOGY  Histologically, 90% of bladder cancers are of urothelial origin, 5% are squamous cell carcinomas, and less than 2% are adenocarcinoma or other variants.  At initial presentation, 80% of urothelial tumors are non–muscle invasive.  There are multiple growth patterns of urothelial cancer, including flat carcinoma in situ (CIS), papillary tumors that can be low or high grade, and sessile tumors with a solid growth pattern
  • 8. WHO Classification of Noninvasive and Invasive Urothelial Neoplasia  Noninvasive Urothelial Neoplasia  Hyperplasia (flat and papillary)  Reactive atypia  Atypia of unknown significance  Urothelial dysplasia (low-grade intraurothelial neoplasia)  Urothelial carcinoma in situ (high-grade intraurothelial neoplasia)  Urothelial papilloma  Urothelial papilloma, inverted type  Papillary urothelial neoplasm of low malignant potential  Noninvasive low-grade papillary urothelial carcinoma  Noninvasive high-grade papillary urothelial carcinoma  Invasive Urothelial Neoplasia  Lamina propria invasion  Muscularis propria (detrusor muscle) invasion
  • 9. STAGING PRIMARY TUMOR (T)  TX Primary tumor cannot be assessed  T0 No evidence of primary tumor  Ta Noninvasive papillary carcinoma  Tis Carcinoma in situ: “flat tumor”  T1 Tumor invades subepithelial connective tissue  T2 Tumor invades muscularis propria pT2a Tumor invades superficial muscularis propria (inner half) pT2b Tumor invades deep muscularis propria (outer half)  T3 Tumor invades perivesical tissue: pT3a Microscopically pT3b Macroscopically (extravesical mass)  T4 Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall  T4a Tumor invades prostatic stroma, uterus, vagina  T4b Tumor invades pelvic wall, abdominal wall
  • 10. REGIONAL LYMPH NODES (N)  NX Lymph nodes cannot be assessed  N0 No lymph node metastasis  N1 Single regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node)  N2 Multiple regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node metastasis)  N3 Lymph node metastasis to the common iliac lymph nodes
  • 11. Distant Metastasis (M)  M0 No distant metastasis  M1 Distant metastasis
  • 12. Anatomic Stage Group T N M  Stage 0a Ta N0 M0  Stage 0is Tis N0 M0  Stage I T1 N0 M0  Stage II T2a N0 M0 T2b N0 M0  Stage III T3a N0 M0 T3b N0 M0 T4a N0 M0  Stage IV T4b N0 M0 Any T N1-3 M0 Any T Any N M1
  • 13. DISSEMINATION A) Angiolymphatic Invasion : seen in approximately 25% of invasive urothelial carcinoma. B) Pagetoid Spread : Pagetoid spread occurs when cancer cells grow underneath a layer of normal-appearing surface urothelium. -Pagetoid spread of urothelial cancer can occur into the prostatic urethra and distal ureters. -Biopsies of normal-appearing prostatic urothelium are needed in the evaluation of patients with positive urine cytology and yet endoscopically normal bladder C) Direct Extension : Direct extension of tumors into the basal lamina, connective tissue, and, ultimately, the angiolymphatic system is caused by genetic and epigenetic changes.
  • 14. DETECTION OF UROTHELIAL CARCINOMA  Gross, painless hematuria is the primary symptom in 85% of patients  Fifty percent of patients with gross hematuria will have a demonstrable cause, 20% will have a urologic malignancy, and 12% will have a bladder tumor  The AUA guidelines for microscopic hematuria evaluation include a cystoscopy, upper tract imaging, and urine cytology
  • 15. INVESTIGATIONS 1) URINE CYTOLOGY -Positive urine cytology is virtually diagnostic of a bladder tumor -the gold standard urinary marker against which other markers are held - the sensitivity and specificity for cytology in detecting bladder cancer is 40% to 62% and 94% to 100%, respectively.
  • 16. 1) 2) CYSTOSCOPY A) White light cystoscopy (WLC) is the gold standard. - White light cystoscopy has an excellent sensitivity of 87% and specificity of 85% for papillary tumors but is relatively poor for CIS (15%). B) Blue light cystoscopy : Porphyrin-induced fluorescence cystoscopy uses photoactive porphyrins, such as hexaminolevulinate, that accumulate preferentially in neoplastic tissue and emit red fluorescence under blue-wavelength light. -This may improve the detection of small papillary lesions and CIS. - Blue light cystoscopy detected 58% of CIS ; and sensitivity of 87%
  • 18. C) Narrow-band imaging (NBI) is an endoscopic optical image enhancement technique that enhances the contrast between mucosal surfaces and microvascular structures without the use of dyes. - vascular structures appear dark brown or green against a pink or white mucosal background. - sens. 100% and sp.82% -NBI more accurately detects tumor recurrence after BCG therapy than do urine cytology or white light cystoscopy,
  • 19. 3) RANDOM BLADDER BIOPSY -Random bladder biopsies are recommended to detect unsuspected CIS or small papillary tumors in endoscopically normal urothelium. - Overall, there is a 2.5% detection rate of CIS or small papillary tumors in random biopsies of patients with known or suspected bladder tumors. -It is reasonable to perform random biopsies in high-risk individuals, such as for those given postintravesical therapy or for those with a positive cytology and an endoscopically negative bladder.
  • 20. 4) URINE MARKERS -There are various urine markers that evaluate secreted proteins or shed cells in the hope of noninvasively detecting bladder cancer. -To date, none of these markers have a high enough sensitivity or specificity to replace office cystoscopy.
  • 21. MARKER MEDIAN SENSITIVITY (%) MEDIAN SPECIFICITY (%)  BTA stat 70 75  BTAtrak 69 65  NMP22 73 80  FDP 61 79  ImmunoCyt 83 80  Cytometry 60 80  Quanticyt 59 79  Hb-dipstick 52 82  Lewis X 83 85  FISH 84 95  Telomerase 75 86  Microsatellite 91 94  CYFRA21-1 94 86  UBC 78 91  Cytokeratin 20 91 84  BTA 50 86  TPS 72 78
  • 22. NON–MUSCLE-INVASIVE BLADDER CANCER  DEF : malignant urothelial tumors that have not invaded the detrusor are more appropriately termed non–muscle invasive traditionally known as superficial bladder cancer .  Approximately 70% are non–muscle invasive at presentation. Of these, 70% present as stage Ta, 20% as T1, and 10% as CIS
  • 23.  Stage Ta tumors are usually low grade. Although recurrence is common, especially in the setting of multiplicity, progression is rare .  Between 40% and 83% of patients with CIS will develop muscle invasion if untreated.  T1 tumors are usually papillary. Deep penetration into the lamina propria, especially if involving muscularis mucosae, increases the risk of recurrence and progression
  • 24. Non-Muscle Invasive Bladder CancerNon-Muscle Invasive Bladder Cancer
  • 26.  There is significant potential for understaging in patients with high-grade, apparently non–muscle-invasive tumors, especially for those that appear to be stage T1.  one third of patients believed to have non–muscle-invasive disease at the time of cystectomy were found to actually have muscle invasion, only half of which were organ confined. Metastases were already present in 8% of these patients.
  • 27. NMIUCNMIUC PrognosisPrognosis correlates with:correlates with:  Tumor gradeTumor grade  +/- CIS+/- CIS  Tumor SizeTumor Size  MultiplicityMultiplicity  Papillary vs SessilePapillary vs Sessile  +/- Lymphovascular Invasion+/- Lymphovascular Invasion
  • 28. ENDOSCOPIC SURGICAL MANAGEMENT  TUR of bladder tumor (TURBT) under regional or general anesthesia is the initial treatment for visible lesions and is performed to (1) remove all visible tumors and (2) provide specimens for pathologic examination to determine stage and grade.  Bimanual examination of the bladder should be performed under anesthesia before prepping and draping unless the tumor is clearly small and noninvasive, and it should be repeated after resection.
  • 29.  Fixation or persistence of a palpable mass after resection suggests locally advanced disease.  Friable, low-grade tumors can often be removed without the use of electrical energy  If a tumor appears to be muscle invasive, biopsies of the borders and base in order to establish invasion may be performed in lieu of complete resection, because cystectomy will likely follow based on confirmatory biopsies  Consensus is that patients with pT1 and high-grade Ta tumors merit repeat resection after 2 to 3 weeks
  • 30. A, Broad-based papillary lesion. B, Resection of lesion with loop electrocautery. C, Depth of resection to detrusor muscle.
  • 31. Complications of Transurethral Resection of Bladder Tumor - Minor bleeding - irritative symptoms - uncontrolled hematuria - clinical bladder perforation -TUR Syndrome --UO Obstruction
  • 32. Why Do Patients Recur?  Nature of the tumor…  Missed tumors at TURBT  Incomplete TURBT resection  Implantation of shed tumor cells at TURBT
  • 33. Perioperative Intravesical Therapy to Prevent Tumor Implantation  It is believed that tumor cell implantation immediately after resection is responsible for many early recurrences and this has been used to explain the observation that initial tumors are most commonly found on the floor and lower side walls of the bladder, whereas recurrences are often located near the dome.  Thus intravesical chemotherapy to kill such cells before implantation has been used
  • 34.  Mitomycin C (MMC) appears to be the most effective adjuvant intravesical chemotherapeutic agent perioperatively.  a single dose administered within 6 hours lessens recurrence rates, whereas a dose 24 hours later does not  Recurrence dropped from 48.4% to 36.7%  Destroys residual microscopic tumor at the TURBT site  Used to prevent tumor implantation  Perforation is absolute contraindication
  • 35. IMMUNOTHERAPYIMMUNOTHERAPY  Goal of immunotherapy is to  Augment cancer cell recognition  Promote tumor cell-specific cytotoxicity  Recruit tumor cells that have evaded the immune system “onto the radar”
  • 36.  Intravesical immunotherapy results in a massive local immune response characterized by induced expression of cytokines in the urine and bladder wall and by an influx of granulocytes, mononuclear, and dendritic cells 1) Bacillus Calmette-Guérin - BCG is an attenuated mycobacterium developed as a vaccine for tuberculosis that has demonstrated antitumor activity in several different cancers including UC -BCG is stored in refrigeration and reconstituted from a lyophilized powder.
  • 37.  Use in CIS  CIS is often diffuse preventing complete tumor resection  80% response rate  50% durable at 4 yrs and 30% at 10 yrs  Higher efficacy compared with intravesical chemo
  • 38.  Use in residual tumor  Effectively treats Ta papillary lesions, but not a surgical substitute  TURP + delayed BCG to prostatic urethra is effective treatment for prostatic CIS  Use as prophylaxis for 6 weeks after TURBT  Induction decreased recurrence by up to 40% for T1 lesions compared to TUR alone  Induction + Maintenance can reduce progression by 20-30% in HG tumors  Maintenance is thought to provide long-term immunostimulation
  • 39. BCG SCHEDULING -Treatments are generally begun 2 to 4 weeks after tumor resection, allowing time for re-epithelialization, which minimizes the potential for intravasation of live bacteria -The vaccine (80-120 mg) is reconstituted with 50 mL of saline and should be administered through a urethral catheter under gravity -In the event of a traumatic catheterization, the treatment should be delayed for several days to 1 week, depending on the extent of injury.
  • 40.  After instillation, the patient should retain the solution for at least 2 hours  Patient should turn from side to side to bathe the entire urothelium  Fluid, diuretic, and caffeine restriction before instillation is essential to limit dilution of the agent with urine and to facilitate retention of the agent for 2 hours
  • 41.  6 week induction alone is insufficient to achieve optimal response  Lamm and SWOG Maintenance – (after 6 week induction)  @ 3 months- 3 weekly instillations  @ 6 months- 3 weekly instillations  then every 6 months for 3 yrs  Quinolones may affect the viability of BCG and should be avoided if possible during the course of BCG treatments
  • 42. CONTRAINDICATIONS  Absolute Contraindications  Immunosuppressed and immunocompromised patients  Immediately after transurethral resection on the basis of the risk of intravasation and septic death  Personal history of BCG sepsis  Gross hematuria (intravasation risk)  Traumatic catheterization (intravasation risk)  Total incontinence (patient will not retain agent)
  • 43.  Relative Contraindications  Urinary tract infection (intravasation risk)  Liver disease (precludes treatment with isoniazid if sepsis occurs)  Personal history of tuberculosis (risk theorized but unknown)  Poor overall performance status  Advanced age  No or Insufficient Data on Potential Need for Contraindications  Patients with prosthetic materials  Ureteral reflux  Anti–tumor necrosis factor medications (theoretically predispose to BCG sepsis)
  • 44. SIDE EFFECTS Grade 1: Moderate Symptoms <48 Hr  Mild/moderate irritative voiding symptoms, mild hematuria, fever <38.5° C  ASSESSMENT  Possible urine culture to rule out bacterial urinary tract infection  SYMPTOM MANAGEMENT  Anticholinergics, analgesics, nonsteroidal anti-inflammatory drugs
  • 45. Grade 2: Severe Symptoms and/or >48 Hr Severe irritative voiding symptoms, hematuria, or symptoms lasting >48 hr All maneuvers for grade 1, plus the following: ASSESSMENT Urine culture, chest radiograph, liver function tests MANAGEMENT Consult immediately with physician experienced in management of mycobacterial infections/complications. Consider dose reduction to one half to one third of dose when instillations resume. Treat culture results as appropriate.
  • 46.  ANTIMICROBIAL AGENTS  Administer isoniazid and rifampins, 300 mg/day and 600 mg/day, orally until symptom resolution.  Do not use monotherapy.  Observe for rifampin drug-drug interactions (e.g., warfarin). Grade 3: Serious Complications (Hemodynamic Changes, Persistent High-Grade Fever)  ALLERGIC REACTIONS (JOINT PAIN, RASH)  Perform all maneuvers described for grades 1 and 2, plus the following:  Isoniazid, 300 mg/day, and rifampin, 600 mg/day, for 3-6 months depending on response
  • 47. SOLID ORGAN INVOLVEMENT (EPIDIDYMITIS, LIVER, LUNG, KIDNEY, OSTEOMYELITIS, PROSTATE) • Isoniazid, 300 mg/day, rifampin, 600 mg/day, ethambutol, 15 mg/kg/ day single daily dose for 3-6 months •Cycloserine often causes severe psychiatric symptoms and is to be strongly discouraged. •BCG is almost uniformly resistant to pyrazinamide, so this drug has no role. •Consider prednisone, 40 mg/day, when response is inadequate or for septic shock (never given without effective antibacterial therapy).
  • 48. 2) INTERFERON -Interferons have multiple antitumor activities * inhibition of nucleotide synthesis; *upregulation of tumor antigens, *antiangiogenic properties; and *stimulation of cytokine release with enhanced T and B cell activation, as well as enhanced natural killer cell activity. -Interferon as a solitary agent is more expensive and less effective than BCG or intravesical chemotherapy in eradicating residual disease, preventing recurrence of papillary disease, and treating CIS -Combination of BCG and interferon is superior
  • 49. 3) NEWER IMMUNOTHERAPEUTIC AGENTS  Keyhole-limpet hemocyanin (KLH) from the hemolymph of the mollusk Megathura crenulata  Bropirimine  Mycobacterial cell wall DNA extract  Thiosulfinate extracts of garlic  Interleukin-12
  • 50. INTRAVESICAL CHEMOTHERAPY  INDICATIONS  Low grade tumor  Multifocal tumor  Recurrences > 4  CIS
  • 51.  Intravesical chemotherapy has a clear impact on tumor recurrence when immediately instilled after TURBT and in the adjuvant setting.  There is no clear evidence of an impact on progression.  Combinations of various chemotherapeutic agents and chemotherapy combined with BCG have not demonstrated major benefit combined with single-agent treatment, with the exception of interferon  Given for 6-8 wks post op. but response not better than BCG
  • 52.  Various chemotherapeutic agents include:  Mitomycin C  Doxorubicin and Its Derivatives  Thiotepa  Gemcitabine and  Taxanes
  • 53. EARLY CYSTECTOMY • Should be considered in patients -Micropapillary Variant – Do not tolerate intravesical therapy – Failed attempts at disease control with TURBT +IVT – Lesions not amenable to endoscopic resection – Failure of TURBT and intravesical therapy • Recurrence at higher grade and multifocality • Progression on intravesical therapy (Grade Progression) • Invasion into detrusor (T progression) • Especially in HGTa or CIS
  • 54. RADIATION THERAPY • Has not been studied extensively in NMI Urothelial Ca • Initial very good response, short term • Not effective long term for Ta or CIS – 90% recur in 5 years
  • 55. AMERICAN UROLOGICAL ASSOCIATION 2007 GUIDELINES FOR NON–MUSCLE-INVASIVE BLADDER CANCER  Index Patient #1: Abnormal Urothelial “Growth” but Not Proven Cancer  Standard: Obtain biopsy to confirm grade for all index patients  If possible, eradicate all visible tumors  If cancer, periodic cystoscopy  Option: Single dose of postoperative intravesical chemotherapy
  • 56.  Index Patient #2: Small-Volume, Low-Grade Ta Recommendation: Single dose of postoperative intravesical chemotherapy  Index Patient #3: Multifocal or Large Low- Grade Ta, or Recurrent Low-Grade Ta  Recommendation: Intravesical BCG or MMC— goal to prevent/delay recurrence  Option: Maintenance BCG or MMC  Index Patient #4: High-Grade Ta, T1, or CIS  Standard: If T1 disease, but no muscularis in specimen, repeat resection  Recommendation: Intravesical BCG with maintenance therapy  Option: Consider cystectomy for select patients
  • 57.  Index Patient #5: High-Grade Ta, T1, and/or CIS Following Prior Intravesical Therapy  Standard: T1 disease but no muscularis in specimen, repeat resection  Recommendation: Consider cystectomy as therapeutic alternative  Option: Further intravesical therapy may be considered
  • 58. INVASIVE BLADDER CANCER DEF. : It includes T2 and beyond bladder cancer  The majority (80%) of patients with bladder cancer present de novo with muscle-invasive disease as its first manifestation.  The remaining 15% to 20% progress from non–muscle-invasive cancer after treatment with intravesical therapy.  Deaths due to bladder cancer invariably occur as a result of distant metastases present at the time of loco-regional therapy.  Progression of cancer after definitive loco-regional therapy commonly occurs within the first 2 years after treatment
  • 59. STAGING AND EVALUATION  Laboratory testing at a minimum should include  complete hemogram,  blood urea,  creatinine,  electrolytes,  liver function tests
  • 60.  IMAGING STUDIES:  CXR  CT Abd & pelvis  CT Chest  Bone scan  MRI  PET  Tumor markers- CEA,CA19.9,CA 125
  • 61. MANAGEMENT  I) SURGICAL  II) NEOADJUVANT CHEMOTHERAPY  III)ADJUVANT CHEMOTHERAPY
  • 62. SURGICAL  I) RADICAL CYTECTOMY  II) BLADDER PRESERVATION SURGERY
  • 63. Indications for radical cystectomy  Infiltrating muscle-invasive bladder cancer without evidence of metastasis or with low-volume, resectable locoregional metastases (stage T2-T3b)  Superficial bladder tumors characterized by any of the following:  Refractory to cystoscopic resection and intravesical chemotherapy or immunotherapy  Extensive disease not amenable to cystoscopic resection  Invasive prostatic urethral involvement  Primary adenocarcinoma, SCC, or sarcoma
  • 64.  Stage-pT1, grade-3 tumors unresponsive to intravesical BCG vaccine therapy  CIS refractory to intravesical immunotherapy or chemotherapy  Palliation for pain, bleeding, or urinary frequency
  • 65. RADICAL CYSTECTOMY  Radical Cystectomy  Removal of bladder with surrounding fat  Prostate/seminal vesicles (males)  Uterus/cervix/fallopian tubes/ovaries /ant. Vault of vagina (females)  + Urethrectomy  Pelvic Lymphadenectomy  More is better  Urinary Diversion  Conduit urinary diversion  Continent cutaneous reservoir  Orthotopic neobladder
  • 66. Radical Cystectomy  Midline incision  Thorough intraabdominal exploration (rule out metastatic disease)  Assess resectability of bladder
  • 67. Step 1: mobilize the urachus from the umbilicus
  • 68. Step 2: mobilize the bladder from the bowel
  • 69. Step 3: isolate and transect ureters
  • 70. Step 4: complete lymph node dissection
  • 71. Step 5: separate bladder from sigmoid colon
  • 72. Step 6: complete posterior dissection and cut off bladder blood supply
  • 73. Step 7: complete anterior dissection and isolate urethra
  • 74. Step 8: transect urethra and remove specimen
  • 75. Cystectomy is not performed when (1)lymph node metastases are unresectable because of bulk or proximal extent above the common iliac vessels; (2) there is evidence of extensive periureteral disease; (3) the bladder is fixed to the pelvic sidewall; or (4) tumor is invading the rectosigmoid colon.
  • 76. PELVIC LYMPHADENECTOMY  ~25% have LN involvement at cystectomy  25 nodes be the minimum number to be removed  Accurate staging  Assessment of prognosis  Adjuvant therapies (chemotherapy, clinical trials)  Therapeutic benefit  Removal of micrometastatic disease
  • 77. Standard LNDStandard LND ExtendedExtended LND Pelvic Lymphadenectomy
  • 78. Urinary Diversion  Use of intestinal segment to bypass/ reconstruct/ replace the normal urinary tract  Goals:  Storage of urine without absorption  Maintain low pressure even at high volumes to allow unobstructed flow of urine from kidneys  Prevent reflux of urine back to the kidneys  Socially-acceptable continence  Empties completely  “Ideal” diversion has yet to be discovered
  • 79. Types of Urinary Diversion ILEAL CONDUIT (incontinent diversion to skin) CONTINENT CUTANEOUS RESERVOIR (continent diversion to skin) ORTHOTOPIC NEOBLADDER (continent diversion to urethra) Figures from www.clevelandclinic.org/health/health-info/docs
  • 80. Ileal Conduit  15-20 cm of small intestine (ileum) is separated from the intestinal tract  Intestines are sewn back together (re- establish intestinal continuity)
  • 81. Ileal Conduit  Ureters are attached to one end of the segment of ileum  Natural peristalsis of intestine propels urine through the segment  Other end is brought out through an opening on the abdomen ureter ureter Ileum
  • 82. Ileal Conduit ADVANTAGES  Simplest to perform  Least potential for complications  No need for intermittent catheterization  Less absorption of urine DISADVANTAGES  Need to wear an external collection bag  Stoma complications  Parastomal hernia  Stomal stenosis  Long-term sequelae  Pyelonephritis  Renal deterioration
  • 83. Continent Cutaneous Reservoir  Many variations (same theme)  Indiana Pouch, Penn Pouch, Kock Pouch…  All use various parts of the intestine  ileum, right colon most commonly  Reservoir  “Detubularized” intestine- low pressure storage  Continence mechanism  Ileocecal valve (Indiana)  Flap valve (Penn, Lahey)  Intussuscepted nipple valve (Kock)
  • 84. Continent Cutaneous Reservoir INDIANA POUCH Appendix removed Right colon and distal ileum isolated Right colon is opened lengthwise and folded down to create a sphere
  • 85. Continent Cutaneous Reservoir INDIANA POUCH RESERVOIR EFFERENT LIMB (to skin) catheter Ureters attached to back of reservoir (not shown) Continence maintained by ileocecal valve
  • 86. Continent Cutaneous Reservoir ADVANTAGES  No external bag  Stoma can be covered with bandaid DISADVANTAGES  Most complex  Need for regular intermittent catheterization  Potential complications:  Stoma stenosis  Stones  Urine infections
  • 87. Orthotopic Neobladder  Currently the diversion of choice  Studer, T-Pouch, Hautmann, Ghoniem, etc. COMPONENTS:  Internal reservoir – detubularized ileum  Connect to urethra (“efferent limb”)  Urethral sphincter provides continence  “Afferent Limb” – ureteral connection  Antirefluxing (T-Pouch, Kock)  Low pressure isoperistaltic limb (Studer)
  • 88. Orthotopic Neobladder 15-20 cm 44 cm Ureters attache d Connect to urethra Ileum detubularize d Reservoir STUDER ILEAL NEOBLADDER
  • 89. 22 cm 22 cm 15-20 cm Isolation of ileal segment Orthotopic Neobladder
  • 91. Orthotopic Neobladder Afferent Limb Reservoir Opening to urethra
  • 92. Orthotopic Neobladder ADVANTAGES  No external bag  Urinate through urethra  May not need catheterization DISADVANTAGES  Incontinence (10- 30%)  Retention (5-20%)  Risk of stones, UTI’s  Need to “train” neobladder
  • 93. Choice of Urinary Diversion  Disease Factors  Urethral margin  Patient Factors  Kidney function / liver function  Manual dexterity  Preoperative urinary continence/ urethral strictures  Motivation  Surgeon Factors  Familiarity with various types of diversions
  • 94. Urinary Diversions  Enterostomal therapist is CRITICAL for success  Urinary diversions require lifelong follow-up  Imaging (kidneys/ureters/diversion)  Labs (electrolytes, acid-base, B12 levels)  Cancer follow-up (surveillance imaging, cytology)
  • 95. BLADDER PRESERVATION APPROACHES 1) Radical Transurethral Resection of Bladder Tumor (TURBT)  Criteria a) initial occurrence of bladder cancer; b) no CIS; c) size less than or equal to 3 cm; d) stage T2 (no palpable mass); and e) not in the dome or high posterior wall because of the risk of bowel injury
  • 96. 2) Partial Cystectomy  Criteria a) Same as for TURBT plus b) Located at dome and away from the ureteral orifices. Bilateral pelvic lymphadenectomy is performed at the time of surgery for pathologic staging of the nodes
  • 97. 3) Trimodality Therapy TURBT + CHEMO + RT Criteria a) clinical stage (organ-confined), b) tumor size less than 3 to 5 cm, c) absence of hydronephrosis, d) absence of a palpable mass, and e) unifocal disease
  • 98. Role of neoadjuvant chemotherapy  Chemotherapy before surgery has several advantages.  Therapy is better tolerated before surgery or radiation.  Chemotherapy-related toxicities are considerably less in patients with localized disease than in those with metastatic disease on the basis of performance status.  Patients are often able to tolerate a greater dose intensity and more cycles of chemotherapy preoperatively than postoperatively.  Neoadjuvant chemotherapy allows in vivo drug sensitivity testing that may provide useful information for later therapy.
  • 99.  The primary tumor can be evaluated for response, which also has major prognostic significance.  In addition, preoperative chemotherapy may down-stage tumors, potentially allowing for technically easier surgery  DISADVANTAGE  delay in definitive local therapy in patients who do not respond or whose disease progresses.  An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy has even been associated with a poorer outcome.  increase in the incidence of perioperative morbidity.
  • 100. ADJUVANT CHEMOTHERAPY  In patients with pT3-4 and/or N+M0 disease, 5-year survival after radical cystectomy is only 25% to 35% at best.  As a result, adjuvant chemotherapy has been advocated for high- risk patients in an effort to delay recurrence and prolong survival  ADVANTAGES  An adjuvant approach allows selection of patients at highest risk of metastatic or recurrent disease on the basis of an accurate pathologic evaluation.  Surgery is performed without delay, and the advent of orthotopic neobladders and continent urinary diversions has improved quality of life in patients after cystectomy, favoring immediate cystectomy.
  • 101.  There is evidence that delaying cystectomy can be detrimental (, and no time is wasted in those patients who do not respond to chemotherapy.  The availability of sufficient tissue for increasingly sophisticated analysis of molecular prognostic and predictive markers is also a potential advantage.  If micrometastases are present, they can be treated with chemotherapy when at a low volume, rather than after there is overt metastatic disease.
  • 102.  DISADVANTAGES  bladder is not preserved and that there is a delay in starting systemic therapy for occult metastases while the focus is first on the primary tumor.  Response cannot be easily evaluated, and the only clinical end point that can be assessed is the time to tumor recurrence  difficulty in administering chemotherapy to those with surgical morbidities following cystectomy.
  • 103. ROBOTIC AND LAP. RADICAL CYSTOPROSTATECTOMY  Robotic-assisted and lap. radical cystectomy represents an evolving field in urology.  It is certainly one tool that can be used in the treatment of invasive bladder cancer.  Morbidity is limited, operative time is comparable, and long-term oncologic outcomes are awaited.

Notes de l'éditeur

  1. Surgery for bladder cancer can really be divided into 3 main components: First, the radical cystectomy which is removal of the bladder with its surrounding fat. In males that also routinely includes the prostate and seminal vesicles, and in women, the uterus, cervix, tubes, and ovaries. Depending on the stage of disease, the urethra may also need to be removed. The removal of the pelvic lymph nodes is also a critical component to the completeness of the surgical resection. And finally, the urinary diversion which typically has the most direct impact on the patient’s quality of life.
  2. The radical cystectomy is performed through a long midline incision. This allows for a thorough intraabdominal exploration to first rule out any obvious metastatic spread which might not have been evident on the preoperative imaging studies. It also allows direct assessment of the bladder to ensure that it can be safely removed.
  3. Despite our CT scans and MRI’s, still about 25% of patients who go into surgery without any evidence of spread outside of the bladder will be found to have positive lymph nodes once the specimen is analyzed. A properly performed pelvic lymphadenectomy provides accurate staging and therefore a better idea of the prognosis. Those patients with lymph node involvement should be considered for other treatments such as chemotherapy or inclusion in clinical trials. It was once thought that once the tumor had spread to the lymph nodes, that “the cat was out of the bag” so to speak and that there was little benefit to doing a thorough lymph node removal. However, there is now increasing evidence to suggest that there is a therapeutic benefit to removing these nodes and that some patients can be cured of their disease with surgery.
  4. One of the current controversies in the Urologic community is what is the optimal extent of the lymph node dissection. For a long time, the standard dissection would include only the lower pelvic nodes directly around the bladder. Several studies have recently supported a more extended dissection to include the nodes around the lower portions of the aorta and inferior vena cava.
  5. Now for the part of the talk that I think most of you are interested in- the urinary diversion. This is basically using a portion of the intestine to bypass, reconstruct, or replace the normal urinary tract. The goals of a urinary diversion are straight forward: To store urine without absorption of the waste products. To store that urine at low pressures so that the urine can continue to drain from the kidneys. To prevent reflux of urine back into the kidneys. To hold on to the urine until it is socially-acceptable to empty, and then to empty completely. If you think about it, this is what our normal bladders do everyday. Having said that, the ideal form of diversion has yet to be discovered.
  6. There are 3 main types of diversions practiced at this time. The ileal conduit which is an incontinent diversion to the skin. This is also known as a urostomy in which an external bag collects the urine continuously. Beginning in the 1980’s we started performing more complex reconstructions, in which a continent reservoir was constructed with an opening to the skin which would then have to be catheterized in order to empty. And it really wasn’t until the 1990’s that the neobladder became popular, which is a continent diversion connected to the native urethra.
  7. The ileal conduit is created from 15-20 cm of small intestine (ileum). This segment of intestine is separated from the rest of the intestinal tract. The intestines are obviously sewn back together so that one can still have bowel movements.
  8. The ureters that drain the kidneys are then sewn into one end of the ileum. And the other end is brought up to an opening on the abdomen as a stoma. The intestine naturally has a propulsive movement, almost like a snake, that normally would be moving food through the GI tract, but in this instance, is pushing the urine through the segment and out of the body.
  9. So for each of these diversions, I’m going to give you a breakdown of the advantages and disadvantages. For the conduit, the advantage is that it is simple to perform. Arguably, it has the least potential for complications. There is no need for catheterization, and because of the movement of the intestine, there is less time for absorption of the urine in the intestine. The disadvantages are that you need to wear an external collection bag. There can be problems with the stoma- either a hernia or scarring making it difficult for the urine to pass. Some long-term problems that have been noted include risks of infections and decreased function of the kidneys after many years.
  10. For the continent cutaneous reservoir- These go by many names with slight variations but all with a similar theme. You may hear these referred to as an Indiana pouch, or a Kock pouch. All use various parts of the intestine, most commonly the ileum and right colon. The intestine is detubularized to create a low pressure storage reservoir. The main difference between these pouches are in terms of how they provide continence. The Indiana uses the natural valve between the small and large intestine called the ileocecal valve. This normally prevents the stool in the colon from backing up into the small intestine. A variety of other techniques have been created to also prevent leakage from the reservoir, including flap valves and nipple valves.
  11. The Indiana Pouch is probably the most commonly used cutaneous reservoir. Here, the right colon and ileum are isolated. The appendix is removed. The right colon is opened lengthwise and folded down to create a sphere.
  12. The ureters are attached to the back of the reservoir and the ileum becomes that efferent limb that is brought up to the skin opening. Continence is maintained by this one way ileocecal valve. So that the only way to empty the reservoir is by passing a catheter through the skin opening through the efferent limb (or ileum) and into the pouch. This needs to be done at regular intervals throughout the day, usually every 4-6 hours.
  13. The main advantage of this type of reservoir is that no external bag is needed. The stoma can be covered with a bandaid. The disadvantages can be quite significant. It is much more complex to create than the ileal conduit. It does require regular intermittent catheterization every 4-6 hours. There are potential for complications with scarring at the stoma making it difficult to catheterize. Urine infections and stones can form within the reservoir since the urine is sitting in there for longer periods of time.
  14. Just as with the catheterizable cutaneous diversions, there are a number of different type of neobladders, though all are based on the same principles. The internal reservoir is created from detubularized intestine. The continence mechanism here is the body’s own urethral sphincter that we naturally depend upon for our urine control normally. The main differences between the various neobladders is how the ureters are attached to the reservoir.
  15. The most commonly performed neobladder is called the Studer neobladder after a European urologist. 44 cm of ileum is set aside for the reservoir and an additional 15-20 cm is for the afferent limb. The ureters are attached to this afferent limb which then drains down into the detubularized 44 cm reservoir, which is then connected to the urethra.
  16. This is how it looks in the operating room. The intestine is separated from the rest of the intestinal tract
  17. The lower 44 cm portion is opened up and fashioned into a patch.
  18. This patch is then folded and closed to become a sphere. And this is the finished product. The ureters are sewn into the afferent limb on the left and the other end is sewn to the urethra.
  19. The advantages: no external bag, ability to urinate through the urethra, and you may not need to do any catheterization. There are significant risks of incontinence (10-30%) which would require pads. There is also a risk of retention of urine that might require intermittent catheterization, which appears to be higher in females for whatever reason. Similar to the Indiana Pouch, there is a risk of stone and UTI’s. It does take some effort to train the neobladder. Patients do need to be very motivated to learn to urinate at regular intervals, practice exercises to control the urine, and to basically learn how to empty the neobladder through a combination of pelvic floor relaxation and abdominal straining.
  20. With all of these options, how does one decide. Well, I think there are really 3 main factors that go into the decision. First is the bladder cancer itself. If the cancer involves the urethra, it does not make sense to create a fancy diversion and connect it to any area where there is cancer. So, if the urethra is involved, the urethra is removed and one of the skin diversions is performed. Secondly, patient factors are clearly important. Due to the potential for absorption of the urine through the intestine, a continent diversion requires normal kidney and liver function to compensate. Good manual dexterity is needed for diversions that may require intermittent catheterization. It’s good to know if there are any preexisting problems with the urethra or urinary sphincter when considering a neobladder. The continent diversions do require a bit of work and patients do need to be motivated to take care of themselves, catheterize when needed, and to be diligent about medical followup to prevent problems down the road. And finally, the surgeon’s familiarity and experience will also play into the choice of diversion.
  21. One of the keys to success is having a dedicated enterostomal therapist or nurse specialist who can work with patients both before and after surgery. I’ve been very fortunate at Loyola to have Ginger Lewis who is an incredible resource for my patients and who has been instrumental in leading our active bladder cancer support group. All of these urinary diversions require lifelong followup. This includes periodic imaging of the kidneys, ureters, and diversion, regular blood work, as well as the routine follow-up for surveillance of the cancer.