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, supraclavicular lymphadenopathy

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
Flourescent cystoscopy
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
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