transitional cell carcinoma of urinary bladeder

TRANSITIONAL CELL TRANSITIONAL CELL CARCINOMA OF URINARY CARCINOMA OF URINARY

BLADEDERBLADEDER

Presented byPresented by

DR. Md.Rezaul KarimDR. Md.Rezaul KarimFCPS (Surgery)FCPS (Surgery)

MS Urology Thesis Part StudentMS Urology Thesis Part Student

Urology Department, BSMMU, Dhaka.Urology Department, BSMMU, Dhaka.

Incidence : sex & raceIncidence : sex & race

Second most Second most common GU cancercommon GU cancer 53,200 new case diagnosed annually in USA, 53,200 new case diagnosed annually in USA,

(33%) in 2000.(33%) in 2000. M:FM:F ratio is ratio is 2-3:12-3:1 Black : whiteBlack : white ratio ratio 4:14:1 Average age at diagnosis (65-69 yrs)Average age at diagnosis (65-69 yrs)

Mean age-Mean age- Male 69yr, Female 74 yr, Male 69yr, Female 74 yr,

Adolescent & youngAdolescent & young >30-40 yr (more indolent). >30-40 yr (more indolent).

Etiology & Risk factorsEtiology & Risk factors

Risk factors are Risk factors are

Cigarette smokingCigarette smoking Lather industriesLather industries

Textile industriesTextile industries Analgesics (phenacetin)Analgesics (phenacetin)

Rubber fire industryRubber fire industry CyclophosphamideCyclophosphamide

Hair dresser, PainterHair dresser, Painter Chronic irritationChronic irritation

Metal works Metal works RadiotherapyRadiotherapy

Tryptophan metabolitesTryptophan metabolites Coffee & tea drinkingCoffee & tea drinking

Artificial sweetenersArtificial sweeteners Schistosoma Schistosoma haematobiumhaematobium

Risk factorsRisk factors

Others:Others: Black foot diseaseBlack foot disease

Arsenic ingestionArsenic ingestion

Chinese herb nephropathyChinese herb nephropathy

Heridity:Heridity:

slightly elevated in relatives ( in smokers)slightly elevated in relatives ( in smokers)

Genetic:Genetic:

Oncogenes- p21 ras mutation – high hist. gradeOncogenes- p21 ras mutation – high hist. grade

Tumor suppressor gene- p53 high hist. grade, del 17pTumor suppressor gene- p53 high hist. grade, del 17p

pRb-aggressive TCCpRb-aggressive TCC

Loss of ch. 9 – both low & high gradeLoss of ch. 9 – both low & high grade

ch. 11 – cHa-ras in 40% bladder cancer.ch. 11 – cHa-ras in 40% bladder cancer.

Clinical carcinogensClinical carcinogens

Exogenous carcinogensExogenous carcinogens αα & & ββ naphthylamine naphthylamine BenzidineBenzidine 4-aminobiphenyl4-aminobiphenyl CyclophosphamideCyclophosphamide Phenacetin, artificial sweetenersPhenacetin, artificial sweeteners Endogenous Endogenous carcinogenscarcinogens Nitrosamine, tryptophane metabolitesNitrosamine, tryptophane metabolites

PathologyPathology

Bladder papillomaBladder papilloma stage 0, benign condition, rare malig. transforamtionstage 0, benign condition, rare malig. transforamtion

but some associates with TCCbut some associates with TCC 3% progress to frank carcinoma, recurrence -47%3% progress to frank carcinoma, recurrence -47% Carcinoma in situCarcinoma in situ velvety patch of erythematous mucosavelvety patch of erythematous mucosa

consists of poorly differentiated TCC confined to consists of poorly differentiated TCC confined to urotheliumurothelium

focal or diffuse, concomitantfocal or diffuse, concomitant

Carcinoma in situ cont..Carcinoma in situ cont..

High rate of recurrence >80%High rate of recurrence >80%

may be asymptomatic or present with urinary frequency, may be asymptomatic or present with urinary frequency, urgency, dysuriaurgency, dysuria

urine cytopathology positive – 80- 90%.urine cytopathology positive – 80- 90%.

Rapidly shades in urine.Rapidly shades in urine. Cystoscopic appearance – cystitis.Cystoscopic appearance – cystitis. Bears a very bad prognosis. Bears a very bad prognosis.

Pathology cont..Pathology cont.. TCCTCC - >90% - >90% papillary (70%), sessile (invasive), infiltrating, papillary (70%), sessile (invasive), infiltrating,

nodular(20%), mixed (20%), flat intraepithelial (CIS). nodular(20%), mixed (20%), flat intraepithelial (CIS). Papillary tumor are superficial.Papillary tumor are superficial.

Relative tumor frequency in urinary bladderRelative tumor frequency in urinary bladder Posterior & lateral wall- 70%Posterior & lateral wall- 70% Trigone & bladder neck- 20%Trigone & bladder neck- 20% Vault of bladder – 10%Vault of bladder – 10% Diverticulum - <1%Diverticulum - <1%

Staging of TCCStaging of TCC

Jewett- Marshall staging systemJewett- Marshall staging system Stage 0-Stage 0- CIS or superficial papillary tumor confined to the CIS or superficial papillary tumor confined to the

mucosa with no invasionmucosa with no invasion Stage A-Stage A- Papillary tumor invading the lamina propria Papillary tumor invading the lamina propria Stage B1-Stage B1- Tumor with superficial muscle invasion Tumor with superficial muscle invasion Stage B2-Stage B2- Tumor with deep muscle invasion Tumor with deep muscle invasion Stage C-Stage C- Invasion of the perivesical fat Invasion of the perivesical fat Stage D1-Stage D1- Involvement of adjacent viscera and/ or pelvic Involvement of adjacent viscera and/ or pelvic

nodesnodes Stage D2 -Stage D2 - Involvement of nodes above the aortic Involvement of nodes above the aortic

bifurcation or distant spread.bifurcation or distant spread.

Staging cont..Staging cont..

TNM ClassificationTNM Classification T =T = primary tumor primary tumor Tx-Tx- primary tumor can’t be assesed primary tumor can’t be assesed Tis-Tis- Carcinoma in situ Carcinoma in situ Ta-Ta- Noninvasive papillary carcinoma Noninvasive papillary carcinoma T1-T1- Tumor invades submucosa/ lamina propria Tumor invades submucosa/ lamina propria T2a-T2a- Tumor invades superficial muscle Tumor invades superficial muscle T2b-T2b- Tumor invades deep muscle Tumor invades deep muscle T3a-T3a- Tumor invades perivesical fat (microscopic) Tumor invades perivesical fat (microscopic) T3b-T3b- Tumor invades perivesical fat (macroscopic) Tumor invades perivesical fat (macroscopic) T4a-T4a- Tumor invades adjacent organ Tumor invades adjacent organ T4b- T4b- Tumor invades pelvic wall, abdominal wall.Tumor invades pelvic wall, abdominal wall.


T1aT1a superficial lamina propria above superficial lamina propria above

muscularis mucosaemuscularis mucosae T1bT1b deep lamina propria beyond deep lamina propria beyond

muscularis mucosaemuscularis mucosae

((Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Richard D. Williams, BJU, 2004)and Richard D. Williams, BJU, 2004)

Seminal vesicle involvement should be included as Seminal vesicle involvement should be included as pT4b.pT4b.

((Prognosis of seminal vesicle involvement by TCC of the bladder, Prognosis of seminal vesicle involvement by TCC of the bladder, Siamak Daneshmand, Jhon P. Stein et al, J of Urol, Vol 172, 81-Siamak Daneshmand, Jhon P. Stein et al, J of Urol, Vol 172, 81-84, Jul’04)84, Jul’04)

TNM Classification cont..TNM Classification cont.. N=N= Regional lymph nodes (below aortic bifurcation) Regional lymph nodes (below aortic bifurcation) NX-NX- Regional lymph nodes can’t be assessed Regional lymph nodes can’t be assessed N0-N0- No regional lymph nodes metastasis No regional lymph nodes metastasis N1-N1- Metastasis in single node < 2 cm Metastasis in single node < 2 cm N2-N2- Metastasis in single node > 2 cm but <5 cm or multiple Metastasis in single node > 2 cm but <5 cm or multiple

nodes < 5 cmnodes < 5 cm N3-N3- Metastasis in nodes >5 cm. Metastasis in nodes >5 cm.

M= M= Distant metastasisDistant metastasis MX-MX- Presence of distant metastasis can’t be assessed Presence of distant metastasis can’t be assessed M0-M0- No distant metastasis No distant metastasis M1-M1- Distant metastasis Distant metastasis


Clinical stagingClinical staging Imaging with US, CT, MRIImaging with US, CT, MRI

CXR, bone scanCXR, bone scan Bimannual palpation after Bimannual palpation after TURBTTURBT No thikening- No thikening- superf. tumorsuperf. tumor

Tumor was palpable- Tumor was palpable- invasive tumorinvasive tumor

Pathological stagingPathological staging ‘‘p’ stagingp’ staging hist. examination of the hist. examination of the

tissue from the base oftissue from the base of resected arearesected area ‘‘P’ stagingP’ staging hist. examination of hist. examination of specimen after radical specimen after radical cystectomy cystectomy


Bimannual palpation after TURBT Bimannual palpation after TURBT No palpable mass No palpable mass T1T1

No mass but thickening No mass but thickening T2 T2 Hard mass Hard mass T3T3 Hard fixed mass Hard fixed mass T4T4

Grading of TCCGrading of TCC

Grade 0-Grade 0- papilloma papilloma Grade 1- Grade 1- well differentiated, Papillary urothelial well differentiated, Papillary urothelial

tumor of low malignant potential (10% will be tumor of low malignant potential (10% will be invasive)invasive)

Grade 2-Grade 2- moderately differentiated, low grade moderately differentiated, low grade urothelial tumor (50% will be invasive)urothelial tumor (50% will be invasive)

Grade 3- Grade 3- poorly differentiated, high grade poorly differentiated, high grade urothelial tumor (>80% will be invasive)urothelial tumor (>80% will be invasive)

Spread of tumorSpread of tumor

Origin:Origin: multicentic, field change diseasemulticentic, field change disease

Direct extensionDirect extension Lymphatic spread-Lymphatic spread- pelvic LN, perivesical 16%, pelvic LN, perivesical 16%,

obturator 74%, exrternal iliac 65%, presacral 25%, obturator 74%, exrternal iliac 65%, presacral 25%, common iliac 20%common iliac 20%

Vascular spread-Vascular spread- liver, lungs, bone, adrenal, liver, lungs, bone, adrenal, intestine.intestine.

Implantation-Implantation- abdominal wound, denuded urothelium, abdominal wound, denuded urothelium, resected prostatic fossa, traumatized urethra- most resected prostatic fossa, traumatized urethra- most commonly with high grade tumor.commonly with high grade tumor.

Natural historyNatural history

55-60%-55-60%- newly diagnosed bl. Cancer are well differentiated or moderately newly diagnosed bl. Cancer are well differentiated or moderately differentiated, majority develop recurrence after TURBT, differentiated, majority develop recurrence after TURBT, 16-25%16-25% with high with high gradegrade

40-45%-40-45%- newly diagnosed bl. Cancer are high grade, more than half muscle newly diagnosed bl. Cancer are high grade, more than half muscle invasive or more extensive at the time of diagnosis, more chance of invasive or more extensive at the time of diagnosis, more chance of recurrence & metastasisrecurrence & metastasis

Low grade tumor have recurrence with high gradeLow grade tumor have recurrence with high grade High & low grade simultaneously not uncommonHigh & low grade simultaneously not uncommon

85-95%85-95% muscle invasive tumor already have invasion at the time of muscle invasive tumor already have invasion at the time of diagnosis, diagnosis,

about about 50%50% muscle invasive tumor already have occult metastsis muscle invasive tumor already have occult metastsis

DiagnosisDiagnosis

History:History:

Painless hematuria (85%-90%), gross/ Painless hematuria (85%-90%), gross/ microscopic; intermittent rather constant.microscopic; intermittent rather constant.

Irritative voiding symptomsIrritative voiding symptoms Flank pain from ureteral obstructionFlank pain from ureteral obstruction Lower leg odema & pelvic painLower leg odema & pelvic pain Bone pain, loss of weight, abdomminal painBone pain, loss of weight, abdomminal pain

DiagnosisDiagnosis

Physical examination:Physical examination: Superficial bl. Carcinoma- no signSuperficial bl. Carcinoma- no sign Palpable mass- at least muscle involvedPalpable mass- at least muscle involved Bimanual palpation at the time of cystoscopy-Bimanual palpation at the time of cystoscopy- movable tumor- stage movable tumor- stage ≥ T3a≥ T3a fixed contiguous structure- stage IVfixed contiguous structure- stage IV Hepatomegaly, supraclavicular lymphadenopa.Hepatomegaly, supraclavicular lymphadenopa. Lymphodema- from pelvic lymphadenopathy.Lymphodema- from pelvic lymphadenopathy. AnaemiaAnaemia

DiagnosisDiagnosis

Investigations:Investigations: Urine analysis and C/SUrine analysis and C/S

Urine for cytolgyUrine for cytolgy

Blood for TC,DC,Hb%,ESRBlood for TC,DC,Hb%,ESR Blood urea & serum creatinineBlood urea & serum creatinine Flow cytometry & image analysisFlow cytometry & image analysis Tumor markers- Tumor markers- BTA, BTA stat, BTA TRAK, NMP 22BTA, BTA stat, BTA TRAK, NMP 22

Cytokeatin 20, lewis x Ag, telomerase activity, HA, HA-ase, Cytokeatin 20, lewis x Ag, telomerase activity, HA, HA-ase,

Investigations cont..Investigations cont..

UroVysin test-UroVysin test- ‘FISH’ analysis ‘FISH’ analysis Sensitivity 81%, Specificity 96%Sensitivity 81%, Specificity 96% HA-HA- more sensitive for low grade (92%, 93%) more sensitive for low grade (92%, 93%) Hyaluroniase-Hyaluroniase- for high grade (100%, 89%) for high grade (100%, 89%) Survivin-Survivin- anti apoptosis protein (100%, 95%) anti apoptosis protein (100%, 95%) detect new or recurrent casesdetect new or recurrent cases Endothelial growth factor, p53, Her-2-neu-Endothelial growth factor, p53, Her-2-neu- more applicable to invasive diseasemore applicable to invasive disease

((Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Richard D. Williams, BJU, 2004, Vol 94: R. Koney and Richard D. Williams, BJU, 2004, Vol 94: 18-21.)18-21.)

DiagnosisDiagnosis

ImagingImaging UltrasoundUltrasound IVUIVU CT scanCT scan MRIMRI CXRCXR Radionuclide bone scanRadionuclide bone scan UrethrocystoscopyUrethrocystoscopy BiopsyBiopsy

Management of superficial Bladder Management of superficial Bladder carcinomacarcinoma

Treatment options:Treatment options: TisTis Complete TUR followed by BCG Complete TUR followed by BCG TaTa( single, low to moderate grade) Complete TUR( single, low to moderate grade) Complete TUR TaTa( large, multiple, high grade, recurrent)-Complete ( large, multiple, high grade, recurrent)-Complete

TUR followed by intravesical Chx or immunotherapyTUR followed by intravesical Chx or immunotherapy T1T1 Complete TUR followed by intravesical Chx or Complete TUR followed by intravesical Chx or

immunotherapy but controversy- high grade-III, immunotherapy but controversy- high grade-III, radical cystectomy if recurrence after a trial needs radical cystectomy if recurrence after a trial needs aggressive treatmentaggressive treatment

Mx of superf. TCC cont..Mx of superf. TCC cont..

Transurethral resection (TUR)Transurethral resection (TUR) Role of ReTURBRole of ReTURB (Effect of routine repeat TUR for superficial bladder cancer: a (Effect of routine repeat TUR for superficial bladder cancer: a

long term observational study, Marc- oliver Grimm, C. Steinhoff long term observational study, Marc- oliver Grimm, C. Steinhoff et al, J of Urol.)et al, J of Urol.)

Complications- perforation, clot retention, ureteric Complications- perforation, clot retention, ureteric orifice strictureorifice stricture

Laser therapy-Laser therapy- Nd:YAG, Holmium, Potassium Nd:YAG, Holmium, Potassium

titanyl phosphate (PTP)titanyl phosphate (PTP)

Photodynamic therapy-Photodynamic therapy-


Intravesical chemotherapy-Intravesical chemotherapy- Mitomycin-C-Mitomycin-C- just after TUR, wkly just after TUR, wkly

40 mg in 60 ml water40 mg in 60 ml water Complications:Complications: chemical cystitis, dec. bladder capacity chemical cystitis, dec. bladder capacity

palmer desquamation.palmer desquamation.

Bacille Calmette Guerin:Bacille Calmette Guerin: M/A-M/A- activity through activation of CD8 cell activity through activation of CD8 cell 40 mg in 60 ml water for 6 wks, 3 wkly at 3 & 6 m40 mg in 60 ml water for 6 wks, 3 wkly at 3 & 6 m every 6 mo thereafter for 3 yrs.every 6 mo thereafter for 3 yrs.(BCG therapy in stage Ta/T1 bladder cancer: prognostic factors for (BCG therapy in stage Ta/T1 bladder cancer: prognostic factors for

time to recurrence and progression,time to recurrence and progression,

P. Andius, S. Holmang, BJU,2004, Vol. 93: 980-984)P. Andius, S. Holmang, BJU,2004, Vol. 93: 980-984)

BCG cont..BCG cont..

Indications:Indications:

Cis, Residual tumor, Tumor prophylaxisCis, Residual tumor, Tumor prophylaxis Contraindications:Contraindications:

immunosuppression, immunocompromised pt. immunosuppression, immunocompromised pt.

relative: poor overall performance, advance age, H/O TBrelative: poor overall performance, advance age, H/O TB

Side effects:Side effects:

hematuria, granulomatous prostatitis, hematuria, granulomatous prostatitis,

fever- Isoniazid 300 mg for 3 mofever- Isoniazid 300 mg for 3 mo

systemic BCGosis- INH+Rifam, Etham for 6 mosystemic BCGosis- INH+Rifam, Etham for 6 mo

BCG sepsis- standard life support, tripple therapyBCG sepsis- standard life support, tripple therapy


ThiotepaThiotepa alkylating agent, 30 mg in 30 ml, wkly for 6 wksalkylating agent, 30 mg in 30 ml, wkly for 6 wks Doxorubicin, epirubicinDoxorubicin, epirubicin Valrubicin-Valrubicin- BCG refractory Cis who can’t tolerate BCG refractory Cis who can’t tolerate cystectomycystectomy Ethoglucid-Ethoglucid- alkylating agent, podophylline alkylating agent, podophylline

derivative.derivative. Combination-Combination- mitomycin(20mg) day 1 mitomycin(20mg) day 1 doxorubicin(40mg) day 2 for 5wkdoxorubicin(40mg) day 2 for 5wk chemotherapy & BCG chemotherapy & BCG

Mx of superf. TCC cont..Mx of superf. TCC cont.. Newer intravesical chemotherapyNewer intravesical chemotherapy

Gemcitabine-Gemcitabine- twice wkly for 6 wks with a 1-wk twice wkly for 6 wks with a 1-wk break after first 3 wks.break after first 3 wks.

salvage intravesical agent for BCG failure.salvage intravesical agent for BCG failure.

Mycobacterial cell wall extract-Mycobacterial cell wall extract- Myco. Phlei. Myco. Phlei.

induction regimen for 6 wks followed by monthly induction regimen for 6 wks followed by monthly maintenance dose maintenance dose

((Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and

Richard D. Williams, BJU, 2004)Richard D. Williams, BJU, 2004)


Other forms of immunotherapy:Other forms of immunotherapy: Interferon(Interferon(αα-2b)- combined with BCG(low dose)-2b)- combined with BCG(low dose)

Keyhole-Limpet HaemocyaninKeyhole-Limpet Haemocyanin

Bropirimine- inducer of IF & NK cellBropirimine- inducer of IF & NK cell

IL12, IL2, TNFIL12, IL2, TNF

Gene therapy:Gene therapy: Cystectomy-Cystectomy- persistent/ recurrentpersistent/ recurrent,,high risk superf. who high risk superf. who

failed to iv Chx., T1 high grade, multifocal.failed to iv Chx., T1 high grade, multifocal.

Mx of superf. TCC cont..Mx of superf. TCC cont.. Alternatives:Alternatives:

External beam radiation therapy-External beam radiation therapy-

refuse cystectomy, unsuitable for major surgeryrefuse cystectomy, unsuitable for major surgery

Chemoprevention:Chemoprevention:

High water intakeHigh water intake

Vitamins-Vitamins- megadoses(vit A,B6,C,E,Zinc) megadoses(vit A,B6,C,E,Zinc)

Difluoromethylornithine-Difluoromethylornithine- enzyme inhibition enzyme inhibition

Soy products-Soy products- phytochemicals phytochemicals

Cyclooxigenase inhibitors-Cyclooxigenase inhibitors- COX2 COX2

Follow upFollow up

Tumor categorized as low, medium & high risk and Tumor categorized as low, medium & high risk and follow up according to riskfollow up according to risk

3 mo for 13 mo for 1stst yr yr

6 mo for 26 mo for 2ndnd yr yr Annually for thereafter.Annually for thereafter. High risk group needs frequent follow up- 1High risk group needs frequent follow up- 1stst at at

6wk6wk Urine cytologyUrine cytology Tumor marker in urine-Tumor marker in urine- NMP 22, Ha-HAase NMP 22, Ha-HAase sesitivity- 50-90%, specificity- 60-90%sesitivity- 50-90%, specificity- 60-90% IVUIVU

Management of invasive and Management of invasive and metastatic bladder cancermetastatic bladder cancer

Treatment options:Treatment options:

T2-T3T2-T3 Radical cystectomy(RC) Radical cystectomy(RC)

Neoadjuvant Chx followed by RCNeoadjuvant Chx followed by RC

Neoadjuvant Chx followed by irradiationNeoadjuvant Chx followed by irradiation

RC followed by adjuvant ChxRC followed by adjuvant Chx

Any stage T,N+,M+Any stage T,N+,M+ Systemic Chx followed by Systemic Chx followed by

selective surgery or irradiationselective surgery or irradiation

Rx of invasive bladder cancer cont..Rx of invasive bladder cancer cont..

Radical cystectomyRadical cystectomy Indications:Indications: Muscle invasive bladder cancer in Muscle invasive bladder cancer in absence of metastasisabsence of metastasis Surgical technique:Surgical technique: Cystectomy, bil. Pelvic lymphadenectomyCystectomy, bil. Pelvic lymphadenectomy

Male- prostate bladder en blockMale- prostate bladder en block Female- uterus, tubes, ovaries, ant wall of vaginaFemale- uterus, tubes, ovaries, ant wall of vagina Nerve sparing modification in maleNerve sparing modification in male Preservation of urethra in male/ female Preservation of urethra in male/ female Role of pelvic lymphadenectomyRole of pelvic lymphadenectomy (Does extended lymphadenectomy increase the morbidity of radical (Does extended lymphadenectomy increase the morbidity of radical

cystectomy? C. Brossner, A. Pycha et al,cystectomy? C. Brossner, A. Pycha et al,

BJU, 2004:Vol 93: 64-66)BJU, 2004:Vol 93: 64-66)

Radical cystectomy cont..Radical cystectomy cont..

Complications: Complications: MortalityMortality 1-2% 1-2%

Morbidity-Morbidity- cardiac arrest, postoperative pul cardiac arrest, postoperative pul embolism, rectal injury, bowel obstr.embolism, rectal injury, bowel obstr. ureteral-enteric anastomotic stricture, meta.ureteral-enteric anastomotic stricture, meta. disorder, vitamin def., chronic UTI, renal disorder, vitamin def., chronic UTI, renal calculous disease, depressioncalculous disease, depression

Radical cystectomy cont..Radical cystectomy cont..

Follow up:Follow up:

tumor recurrence,tumor recurrence,

complication related to interposition of bowelcomplication related to interposition of bowel

Annual screening withAnnual screening with

Physical examination, serum electrolytesPhysical examination, serum electrolytes

Chest X-ray (PT1)Chest X-ray (PT1)

semiannual- (PT2), quarterly- (PT3) with annual semiannual- (PT2), quarterly- (PT3) with annual CT scan. CT scan.

Upper tract imaging-Upper tract imaging- to exclude ureteral stenosis, upper to exclude ureteral stenosis, upper tract tumor.tract tumor.

Treatment cont..Treatment cont..

Adjunct to standard surgical therapyAdjunct to standard surgical therapy Preoperative radiation therapyPreoperative radiation therapy Neoadjuvant Chx Neoadjuvant Chx Perioperative ChxPerioperative Chx Adjuvant ChxAdjuvant Chx Alternatives to standard therapy:Alternatives to standard therapy: Radiation therapy- external beam radiationRadiation therapy- external beam radiation hyperfractionation schedulehyperfractionation schedule T2a- T2a- TUR & BCG immunoprophylaxis who were TUR & BCG immunoprophylaxis who were

unfit for or refused more aggressive surgeryunfit for or refused more aggressive surgery(T2a TCC of the bladder: long-term experience with intravesical (T2a TCC of the bladder: long-term experience with intravesical

immunoprophylaxis with BCG, B. G. Volkmer, J.E. Gschwend et al, J of immunoprophylaxis with BCG, B. G. Volkmer, J.E. Gschwend et al, J of Urol, Vol 169, 931-935, March’2003)Urol, Vol 169, 931-935, March’2003)

Treatment cont..Treatment cont..

Transurethral resection & partial cystectomyTransurethral resection & partial cystectomy TUR , partial cystectomy with ChxTUR , partial cystectomy with Chx Bladder preservation protocol:Bladder preservation protocol: TUR, neoadjuvant Chx (MCV), subsequent RTxTUR, neoadjuvant Chx (MCV), subsequent RTx

Contraindication- presence of HDN, Cis, a tumor that Contraindication- presence of HDN, Cis, a tumor that can’t resect transurethrally.can’t resect transurethrally. Interstitial radiation therapyInterstitial radiation therapy preoperative external beam radiation, TUR or partial preoperative external beam radiation, TUR or partial

cystectomy, susequent Iridium192 wire (low stage T1-T2)cystectomy, susequent Iridium192 wire (low stage T1-T2) Intraarterial ChxIntraarterial Chx ( combined with RC, radiation ) ( combined with RC, radiation ) Hyperthermia and ChxHyperthermia and Chx

Treatment of metastatic bladder Treatment of metastatic bladder cancercancer

Systemic chemotherapySystemic chemotherapy unresectable, diffusely metastaticunresectable, diffusely metastatic MVACMVAC Newer agent- GemcitabineNewer agent- Gemcitabine Taxoids- Docetaxel, paclitaxelTaxoids- Docetaxel, paclitaxel Local salvage and palliative therapyLocal salvage and palliative therapy

Selection of patient for urinary diversion following Selection of patient for urinary diversion following radical cystectomyradical cystectomy

noncontinent divrsion, continent diversionnoncontinent divrsion, continent diversion orthotopic neobladderorthotopic neobladder

CounsellingCounselling

Prognostic indicatorsPrognostic indicators

Clinical & pathological parameters in superf. TCCClinical & pathological parameters in superf. TCC Laboratory parametersLaboratory parameters ( (P53 nuclear accumulationP53 nuclear accumulation)) A,B,H and other blood group antigenA,B,H and other blood group antigen

Lewisx Ag expressedLewisx Ag expressed

ABH – not presentABH – not present Growth factor and their receptorsGrowth factor and their receptors

TGFTGFββ-1-1

Amplification of c-erb-B2 oncogeneAmplification of c-erb-B2 oncogene Chromosomal and genetic abnormalitiesChromosomal and genetic abnormalities

deletion Ch-9, deletion Ch 17p-P53, Ch13q- Rb gene.deletion Ch-9, deletion Ch 17p-P53, Ch13q- Rb gene.

PrognosisPrognosis

Tumor stageTumor stage CisCis PTaPTa PT1PT1 PT2PT2 PT3PT3 PT4PT4

5 year survival5 year survival 90%-100%90%-100% 90%-95%90%-95% 40%-75%40%-75% 55%-60%55%-60% 30%-40%30%-40% 5%-10%5%-10%

What’s newWhat’s new

Staging-Staging- T1a & T1b, T4b (sem. vesicle) T1a & T1b, T4b (sem. vesicle) Tumor markers-Tumor markers- UroVysin, HA,H-ase, SurvivinUroVysin, HA,H-ase, Survivin

Role of Role of ReTURBReTURB New intravesical cheomtherapy-New intravesical cheomtherapy- GemcitabineGemcitabine

Role of Role of lymphadenectomylymphadenectomy in RC in RC Bladder preservationBladder preservation protocol in T2a protocol in T2a with BCG with BCG

Prognostic significancePrognostic significance in seminal vesical in seminal vesical involvement.involvement.

ReferencesReferences

Emil A. Tanagho, Jack W. McAninch;Emil A. Tanagho, Jack W. McAninch; Smith’s General Smith’s General Urology; 16Urology; 16thth edn.; McGraw Hill 2004. edn.; McGraw Hill 2004.

Fagbemi S, Stadler W.Fagbemi S, Stadler W. New Chemotherapy regimens for New Chemotherapy regimens for advanced bladder cancer. Semin Uro Oncol 1998;16:23.advanced bladder cancer. Semin Uro Oncol 1998;16:23.

Gillenwater JY, Grayhack JT;Gillenwater JY, Grayhack JT; Adult and Pediatric Urology; Adult and Pediatric Urology; Mosby 1996.Mosby 1996.

Russel, Williams and Bulstrode;Russel, Williams and Bulstrode; Baily & Love’s short practice Baily & Love’s short practice of surgery; 24th edn; Arnold, 2000.of surgery; 24th edn; Arnold, 2000.

Walsh, Retik, Vaughan & Wein;Walsh, Retik, Vaughan & Wein; Campbell’s urology; 8 Campbell’s urology; 8thth edn.; edn.; W.B. Saunders Company, 2002.W.B. Saunders Company, 2002.

Salam MA;Salam MA; Principles & Practice of Uromlogy; 1 Principles & Practice of Uromlogy; 1stst edn; edn; MAS publication,2002.MAS publication,2002.

transitional cell carcinoma of urinary bladeder

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