Bladder tumorsBladder tumors

• 3 times more common in men3 times more common in men

• 2 times more common in whites2 times more common in whites

• Incidence increase with age, median 70 Incidence increase with age, median 70 yryr

• Never found incidentallyNever found incidentally

• 5 yrs survival is higher in men5 yrs survival is higher in men

• In young (<30-40 yrs) is well In young (<30-40 yrs) is well differentiateddifferentiated

Risk factorsRisk factors

• Cyclophsphamide increase the risk 9 foldCyclophsphamide increase the risk 9 fold

• Pelvic irradiation increase the risk 2 foldsPelvic irradiation increase the risk 2 folds

• Most bladder carcinogens are aromatic Most bladder carcinogens are aromatic aminesamines

• Oncogens are activated mutant gene(RAS)Oncogens are activated mutant gene(RAS)

• Inactivation of tumor suppressor gene(P53) Inactivation of tumor suppressor gene(P53)

•

Bladder cancers (risk Bladder cancers (risk factors)factors)• Cigarette smoking increase risk by 2 foldsCigarette smoking increase risk by 2 folds

• Dose related, causative agent is NaphtylamineDose related, causative agent is Naphtylamine

• Occupational exposureOccupational exposure

• Chemical,dye,rubber,leather,petrolium,printingChemical,dye,rubber,leather,petrolium,printing

• Cyclophosphamide,artificial sweetenerCyclophosphamide,artificial sweetener

• Physical trauma to urotheliun Physical trauma to urotheliun like:infection,calculi,instrumentationlike:infection,calculi,instrumentation

• Deletion of chromosome 9, 17p, 11pDeletion of chromosome 9, 17p, 11p

Bladder cancers (patholgy)Bladder cancers (patholgy)

• 90% of bladder cancers are Transitional cell90% of bladder cancers are Transitional cell• Most commonly are papilary and exophyticMost commonly are papilary and exophytic• Sessile or ulcerative lesions are rare but Sessile or ulcerative lesions are rare but

invasiveinvasive• Grading: cell size, nuclear size, number of Grading: cell size, nuclear size, number of

mitosis, hyperchromatism, nucleolimitosis, hyperchromatism, nucleoli• Carcinoma in situ is a flat, anaplastic Carcinoma in situ is a flat, anaplastic

epitheliumepithelium• May progress to invasive dis.May progress to invasive dis.• Invasion, recurrence and progression is related Invasion, recurrence and progression is related

with tumor gradewith tumor grade

Bladder tumor pathologyBladder tumor pathology

Bladder tumor pathologyBladder tumor pathology

Bladder tumors (pathology)Bladder tumors (pathology)• Adenocarcinoma:<2% of all tumorsAdenocarcinoma:<2% of all tumors

• Are mucus secreting,glandular or colloidAre mucus secreting,glandular or colloid

• Preceeded by cystitis and metaplasiaPreceeded by cystitis and metaplasia

• Often arise along the floor of the bladderOften arise along the floor of the bladder

• Adenocarcinoma of urachus occur at domeAdenocarcinoma of urachus occur at dome

• Often localized at diagnosis but muscle Often localized at diagnosis but muscle invasion usually presentinvasion usually present

• Five years survival is <40% despite Five years survival is <40% despite treatmenttreatment

Bladder cancers (pathology)Bladder cancers (pathology)• Squamous cell carcinoma: 5-10%Squamous cell carcinoma: 5-10%• Chronic infection, chronic catheter use, Chronic infection, chronic catheter use,

vesical calculivesical calculi• Bilharzial infectionBilharzial infection• Nodular, invasive, poorly differentiatedNodular, invasive, poorly differentiated• 60% of bladder cancers in Egypt, middle 60% of bladder cancers in Egypt, middle

east and part of africaeast and part of africa• Mixed carcinoma:4-6%, most common Mixed carcinoma:4-6%, most common

type composed of transitional and type composed of transitional and squamous cell elementssquamous cell elements

symptoms and signssymptoms and signs• Hematuria: 85-90%, gross (70%) or Hematuria: 85-90%, gross (70%) or

microscopic,intermittentmicroscopic,intermittent• Symptoms of vesical irritability Symptoms of vesical irritability

mostly with diffuse CISmostly with diffuse CIS• Bone pain, flank painBone pain, flank pain• Mostly have no signsMostly have no signs• Bimanual examination under Bimanual examination under

anesthesiaanesthesia• Lymphedema, hepatomegaly, Lymphedema, hepatomegaly,

supraclavicular lymphadenopathysupraclavicular lymphadenopathy

Laboratoary findingsLaboratoary findings• Hematuria, pyuria, azotemia, anemiaHematuria, pyuria, azotemia, anemia

• Urine cytology : useful in screening of high Urine cytology : useful in screening of high risk population and assesing response to risk population and assesing response to treatmenttreatment

• Detection rate depend on volume and grade Detection rate depend on volume and grade of tumor and adequacy of specimenof tumor and adequacy of specimen

• Tumor markers : BTA test, NMP22, FDP, Tumor markers : BTA test, NMP22, FDP, telomerase activity, Lewis X antigentelomerase activity, Lewis X antigen

• May have role in initial evaluation, follow-up May have role in initial evaluation, follow-up and prediction of natural history of tumorand prediction of natural history of tumor

Tumor markersTumor markers

• Suitable for survilance but not good Suitable for survilance but not good tool for screeningtool for screening

• BTA and NMP22 have low sensitivity BTA and NMP22 have low sensitivity for small tumorsfor small tumors

• Immunocyst and FISH have higher Immunocyst and FISH have higher sensitivity and specifity but are more sensitivity and specifity but are more expensiveexpensive

Bladder tumor (imaging)Bladder tumor (imaging)• Used to evaluate upper urinary tract, to Used to evaluate upper urinary tract, to

asses the depth of muscle wall infilteration asses the depth of muscle wall infilteration and the presence of regional or distant and the presence of regional or distant metastasismetastasis

• IVP is the most common test for evaluation IVP is the most common test for evaluation of hematuriaof hematuria

• CT & MRI can show the extent of bladder CT & MRI can show the extent of bladder wall invasion and detect pelvic lymph nodewall invasion and detect pelvic lymph node

• Overall staging accuracy is 40-85% for CT Overall staging accuracy is 40-85% for CT and 50-90% for MRIand 50-90% for MRI

• Chest X ray, bone scanChest X ray, bone scan

Natural historyNatural history• IIs defined by tumor recurrence and s defined by tumor recurrence and

progressionprogression• Based on tumor stage,grade,size,multiplicityBased on tumor stage,grade,size,multiplicity• 50-70% of bladder tumors are superficial50-70% of bladder tumors are superficial• 15% with regional and distant metastasis15% with regional and distant metastasis• 55% are low grade and 45% high grade55% are low grade and 45% high grade• 50% of high grade tumors are muscle invasive50% of high grade tumors are muscle invasive• High grade tumor are related with p53 High grade tumor are related with p53

abnormalityabnormality• Low grade tumors related with deletion of long Low grade tumors related with deletion of long

arm of chromosome 9arm of chromosome 9

Natural historyNatural history

• There are strong correlations between There are strong correlations between tumor grade and stage with tumor tumor grade and stage with tumor recurrence, progression and survivalrecurrence, progression and survival

• Tumor recurrence is related to history Tumor recurrence is related to history of disease and grade, number and size of disease and grade, number and size of tumorof tumor

• Most important risk factor for Most important risk factor for progression is grade not stageprogression is grade not stage

• It is more common in the first 12 It is more common in the first 12 monthsmonths

Bladder tummor Bladder tummor (molecular (molecular markers)markers)• Microvessele density detect rate of Microvessele density detect rate of

angiogenesisangiogenesis

• Mutation of P53 gene Mutation of P53 gene

• P53 gene is a tumor suppressor gene that P53 gene is a tumor suppressor gene that plays a key role in the regulation of the plays a key role in the regulation of the cell cyclecell cycle

• Retinoblastoma(Rb) gene is a tumor Retinoblastoma(Rb) gene is a tumor suppressor genesuppressor gene

• Alteration of Rb gene is associated with Alteration of Rb gene is associated with high grade, high stage bladder cancers.high grade, high stage bladder cancers.

DiagnosisDiagnosis

• Cystoscopy and deep biopsyCystoscopy and deep biopsy

• Flourescent cystoscopyFlourescent cystoscopy

• TURTUR

Treatment modalitiesTreatment modalities

• Intravesical Intravesical chemotherapy,immunotherapychemotherapy,immunotherapy

• Transurethral resection of tumorTransurethral resection of tumor

• Partial cystectomyPartial cystectomy

• Radical cystectomyRadical cystectomy

• RadiotherapyRadiotherapy

• ChemotherapyChemotherapy

Treatment selectionTreatment selection• Superficial bladder cancer: TUR followed by Superficial bladder cancer: TUR followed by

intravesical chemotherapy or immunotherapyintravesical chemotherapy or immunotherapy

• More invasive but localized tumor(T2,T3): More invasive but localized tumor(T2,T3): partial or radical cystectomy, radiation or partial or radical cystectomy, radiation or surgery and systemic chemotherapysurgery and systemic chemotherapy

• Unresectable local tumors(T4b) : systemic Unresectable local tumors(T4b) : systemic chemotherapy followed by surgery or chemotherapy followed by surgery or irradiationirradiation

• Local or distant metastasis: systemic Local or distant metastasis: systemic chemotherapy followed by irradiation or chemotherapy followed by irradiation or surgerysurgery

Intravesical chemotherapyIntravesical chemotherapy

• Adjunctive: at TUR to prevent implantationAdjunctive: at TUR to prevent implantation• Prophylactic: after complete TUR to Prophylactic: after complete TUR to

prevent or delay recurrence or progressionprevent or delay recurrence or progression• Therapeutic: after incomplete TUR to cure Therapeutic: after incomplete TUR to cure

residual diseaseresidual disease• Most agents are administered weekly for 6 Most agents are administered weekly for 6

weeksweeks• Local toxicity is common but systemic Local toxicity is common but systemic

toxicity is raretoxicity is rare• Mitomycin C, Thiotepa, Doxorubicin, BCGMitomycin C, Thiotepa, Doxorubicin, BCG

RadiotherapyRadiotherapy

• Alternatve to radical cystectomy in Alternatve to radical cystectomy in deeply infilterating bladder tumotdeeply infilterating bladder tumot

• 5000-7000 cGy over 5-8 week period5000-7000 cGy over 5-8 week period

• Local recurrence is common 33-68%Local recurrence is common 33-68%

• Only for patients who are poor Only for patients who are poor candidate for surgerycandidate for surgery

Systemic Systemic chemotherapychemotherapy• The single most active agent is The single most active agent is

cisplatincisplatin

• MVAC is the most common regimen MVAC is the most common regimen for patients with advanced bladder for patients with advanced bladder cancercancer

• 13-35% show complete response13-35% show complete response

• Gemcitabin, Ifosfamide and cisplatin Gemcitabin, Ifosfamide and cisplatin have lower toxicity than MVAChave lower toxicity than MVAC