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 MicroscopicallypT3b 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 M0T4a N0 M0

Stage IV T4b N0 M0Any T N1-3 M0Any 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%

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 Telomerase75 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 Non-Muscle Invasive Bladder CancerCancer

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 grade Tumor 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 Standard LNDLND Extended Extended

LNDLND

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

ureterureter

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 ReservoirINDIANA POUCH

Appendix removed

Right colon and distal

ileum isolated

Right colon is opened lengthwise and folded down to create a sphere

Continent Cutaneous ReservoirINDIANA POUCH

RESERVOIREFFERENT LIMB

(to skin)

catheterUreters 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 attached

Connect to urethra

Ileum detubularized 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)

Criteriaa) initial occurrence of bladder cancer;b) no CIS; c) size less than or equal to 3 cm;d) stage T2 (no palpable mass); ande) not in the dome or high posterior wall because of the risk

of bowel injury

2) Partial Cystectomy

Criteriaa) 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

Criteriaa) clinical stage (organ-confined),

b) tumor size less than 3 to 5 cm,

c) absence of hydronephrosis,

d) absence of a palpable mass, ande) 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.