Bladder tumors

1. Bladder tumors • 3 times more common in men • 2 times more common in whites • Incidence increase with age, median 70 yr • Never found incidentally • 5 yrs survival is higher in men • In young (<30-40 yrs) is well differentiated

2. Risk factors • Cyclophsphamide increase the risk 9 fold • Pelvic irradiation increase the risk 2 folds • Most bladder carcinogens are aromatic amines • Oncogens are activated mutant gene(RAS) • Inactivation of tumor suppressor gene(P53)

3. Bladder cancers (risk factors) • Cigarette smoking increase risk by 2 folds • Dose related, causative agent is Naphtylamine • Occupational exposure • Chemical,dye,rubber,leather,petrolium,printing • Cyclophosphamide,artificial sweetener • Physical trauma to urotheliun like:infection,calculi,instrumentation • Deletion of chromosome 9, 17p, 11p

4. Bladder cancers (patholgy) • 90% of bladder cancers are Transitional cell • Most commonly are papilary and exophytic • Sessile or ulcerative lesions are rare but invasive • Grading: cell size, nuclear size, number of mitosis, hyperchromatism, nucleoli • Carcinoma in situ is a flat, anaplastic epithelium • May progress to invasive dis. • Invasion, recurrence and progression is related with tumor grade

8. Bladder tumor pathology

9. Bladder tumor pathology

10. Bladder tumors (pathology) • Adenocarcinoma:<2% of all tumors • Are mucus secreting,glandular or colloid • Preceeded by cystitis and metaplasia • Often arise along the floor of the bladder • Adenocarcinoma of urachus occur at dome • Often localized at diagnosis but muscle invasion usually present • Five years survival is <40% despite treatment

11. Bladder cancers (pathology) • Squamous cell carcinoma: 5-10% • Chronic infection, chronic catheter use, vesical calculi • Bilharzial infection • Nodular, invasive, poorly differentiated • 60% of bladder cancers in Egypt, middle east and part of africa • Mixed carcinoma:4-6%, most common type composed of transitional and squamous cell elements

14. symptoms and signs • Hematuria: 85-90%, gross (70%) or microscopic,intermittent • Symptoms of vesical irritability mostly with diffuse CIS • Bone pain, flank pain • Mostly have no signs • Bimanual examination under anesthesia • Lymphedema, hepatomegaly, supraclavicularlymphadenopathy

15. Laboratoary findings • Hematuria, pyuria, azotemia, anemia • Urine cytology : useful in screening of high risk population and assesing response to treatment • Detection rate depend on volume and grade of tumor and adequacy of specimen • Tumor markers : BTA test, NMP22, FDP, telomerase activity, Lewis X antigen • May have role in initial evaluation, follow-up and prediction of natural history of tumor

16. Tumor markers • Suitable for survilance but not good tool for screening • BTA and NMP22 have low sensitivity for small tumors • Immunocyst and FISH have higher sensitivity and specifity but are more expensive

17. Bladder tumor (imaging) • Used to evaluate upper urinary tract, to asses the depth of muscle wall infilteration and the presence of regional or distant metastasis • IVP is the most common test for evaluation of hematuria • CT & MRI can show the extent of bladder wall invasion and detect pelvic lymph node • Overall staging accuracy is 40-85% for CT and 50-90% for MRI • Chest X ray, bone scan

20. Natural history • Is defined by tumor recurrence and progression • Based on tumor stage,grade,size,multiplicity • 50-70% of bladder tumors are superficial • 15% with regional and distant metastasis • 55% are low grade and 45% high grade • 50% of high grade tumors are muscle invasive • High grade tumor are related with p53 abnormality • Low grade tumors related with deletion of long arm of chromosome 9

21. Natural history • There are strong correlations between tumor grade and stage with tumor recurrence, progression and survival • Tumor recurrence is related to history of disease and grade, number and size of tumor • Most important risk factor for progression is grade not stage • It is more common in the first 12 months

22. Bladder tummor (molecular markers) • Microvessele density detect rate of angiogenesis • Mutation of P53 gene • P53 gene is a tumor suppressor gene that plays a key role in the regulation of the cell cycle • Retinoblastoma(Rb) gene is a tumor suppressor gene • Alteration of Rb gene is associated with high grade, high stage bladder cancers.

23. Diagnosis • Cystoscopy and deep biopsy • Flourescentcystoscopy • TUR

26. Treatment modalities • Intravesical chemotherapy,immunotherapy • Transurethral resection of tumor • Partial cystectomy • Radical cystectomy • Radiotherapy • Chemotherapy

27. Treatment selection • Superficial bladder cancer: TUR followed by intravesical chemotherapy or immunotherapy • More invasive but localized tumor(T2,T3): partial or radical cystectomy, radiation or surgery and systemic chemotherapy • Unresectable local tumors(T4b) : systemic chemotherapy followed by surgery or irradiation • Local or distant metastasis: systemic chemotherapy followed by irradiation or surgery

28. Intravesical chemotherapy • Adjunctive: at TUR to prevent implantation • Prophylactic: after complete TUR to prevent or delay recurrence or progression • Therapeutic: after incomplete TUR to cure residual disease • Most agents are administered weekly for 6 weeks • Local toxicity is common but systemic toxicity is rare • Mitomycin C, Thiotepa, Doxorubicin, BCG

31. Radiotherapy • Alternatve to radical cystectomy in deeply infilterating bladder tumot • 5000-7000 cGy over 5-8 week period • Local recurrence is common 33-68% • Only for patients who are poor candidate for surgery

32. Systemic chemotherapy • The single most active agent is cisplatin • MVAC is the most common regimen for patients with advanced bladder cancer • 13-35% show complete response • Gemcitabin, Ifosfamide and cisplatin have lower toxicity than MVAC