This document discusses bladder carcinoma, including its incidence, risk factors, pathogenesis, clinical features, imaging, histopathology, staging, and treatment options. It provides details on transitional cell carcinoma and other rare types. Treatment may involve transurethral resection of the tumor, intravesical chemotherapy or immunotherapy, radical cystectomy, radiation, chemotherapy, or a combination based on the stage and grade of cancer. The goal is to prevent recurrence, progression, and spread to lymph nodes or distant sites.

1. BLADDER CARCINOMA
BY
DR.P.MONIKHA

2. INCIDENCE:
• 2ND M/C cancer of the genitourinary tract
• Average age – 65 yrs
• 75% of bladder –localised to bladder
• 25% spread to regional lymph nodes or distant sites
RISK FACTORS AND PATHOGENESIS :
• cigarette smoking -65% in men and 20 to 30% in women.
• Workers in the chemical ,dye, rubber,petroleum,leather and printing industries are at
increased risk.
• Infection
• Instrumentation
• Calculi

3. p53 tumor suppressor gene mutations –primary ,recurrent and
upper tract tumours
chr 11p contains c-Ha-ras proto oncogene deletion -40% of cancers
chr 17p deletions -invasive bladder cancers 60%
FGFr3 mutations (oncogene) ->60% papillomas and low grade
bladder tumors
Loss of genetic material on chr 9 –low grade ,low stage and high
grade ,high stage disease –early event in cancer development

4. T4a –invasion of prostate,
uterus , vagina
T4b –invasion of pelvic
wall, abdominal wall
•T –PRIMARY TUMOR
•N –LYMPH NODE STATUS
•M –METASTASIS
•Nx –cannot be assessed
•N0 – no nodal metastases
•N1 -single node <2cm involved
•N2 –single node 2-5 cm or multiple node
<5cm
•N3 –One or more >5 cm in size
•Mx –cannot be defined
•M0 –no distant metastases
•M1 –Distant metastases

5. HISTOPATHOLOGY:
•90% -Epithelial malignancies –transitional cell carcinomas
•5% -adenocarcinomas or squamous cell carcinomas
Normal urothelim : 3-7 layers of transitional cell epithelium
basal cells –actively proliferating cells resting on
basement membrane
luminal cells –larger umbrella like cells –bound
together by tight junctions
loose connective tissue
muscularis propria
TRANSITIONAL CELL CARCINOMA:
•90% -TCCs
•Papillary , exophytic lesions
•CIS –flat ,anaplastic epithelium
•Cells –large ,irregular hyperchromatic nuclei with prominent
nucleoli

6. NONTRANSITIONAL CELL CARCINOMAS
ADENOCARCINOMA:
•<2% -Bladder cancers
•Preceded by cystitis and
metaplasia
•Histo : mucus secreting
glandular ,colloid or
signet ring pattern
•Muscle invasion +
•Aggressive T/t
SQUAMOUS CELL
CARCINOMA:
• 5-10% -All cancers
• h/o infection
vesical calculi
chronic catheter use
• Bilharzial infection
• Nodular and
invasive
• Histo :poorly
differentiated –
polygonal cells with
intracellular bridges
UNDIFFERENTIATED
CARCINOMA:
•Rare <2%
•No mature epithelial
elements
•Undifferentiated with
neuroendocrine features
•Small cell carcinoma –
aggrerssive and with
mets
MIXED CARCINOMA:
• 4-6%
• Transitional +
glandular +
squamous +
undifferentiated
• Large and infiltrating

7. RARE EPITHELIAL AND NONEPITHELIAL
CANCERS:
Villous adenomas
carcinoid tumours
carcinosarcomas
melanoma
pheochromocytomas
lymphomas
choriocarcinomas
lymphomas
choriocarcinomas
mesenchymal tumors
prostate ,cervix and rectum –direct extension
Epithelial
Non epithelial

8. CLINICAL FEATURES:
Symptoms:
•Hematuria (85 – 90%)
•Vesical irritability : frequency
dysuria
urgency
•Advanced disease : bone pain from bone mets
flank pain from retroperitoneal mets or ureteral obstruction
Signs:
•Palpable mass or bladder wall thickening
•Non mobile bladder – fixed to underlying structures
•Mets –hepatomegaly or supraclavicular lymphadenopathy
• rare –mets in unusual sites –skin as nodules

9. LABORATORY FINDINGS:
Routines :
•Hematuria
•Anemia
•Azotemia
•Pyuria
Urinary cytology :
•Neoplastic cells in urine
•Large amount through catheter or cystoscope
Other markers :
•BTA stat test (bladder tumor antigen)
•BTA TRAK assay
•NMP 22 Assay
•Immunocyt
•Uro Vysion
Cancer specific proteins in urine
Cytogenetic markers in nucleus

10. IMAGING:
•Confirmation –cystoscopy and biopsy
•Intravenous urography –m/c done for hematuria
•CT urography –accurate for entire abdominal cavity,renal parenchyma and
ureters
•Pedunculated, radiolucent filling defects projecting into lumen; nonpapillary
infiltrating tumors –result in fixation or flattening of the bladder wall
• Hydronephrosis from ureteral obstruction –with infiltrating lesions and poior
outcome
•CT and MRI –extent of bladder invasion and lymph node involvement with
overall staging
•Lymph nodes >1cm –s/o mets
•Mets –lungs (chest x ray) and bones (radionuclide bone scan)
•PET CT scan –mets

11. CYSTOURETHROSCOPY AND TUMOR RESECTION:
•Diagnosis and initial staging –cystoscopy and TUR
•CIS –Flat areas of erythema and mucosal irregularity
•Superficial, low grade tumors –as single or multiple papillary lesions
•Higher grade lesions –larger and sessile
•Tumor visualised or suspected –anesthesia and TUR or biopsy of suspected
lesion
•Objectives : tumor diagnosis
assessment of the degree of bladder wall invasion (staging)
complete excision of the low grade lesions
•Procedure : lithotomy position
BME
Presence of palpable mass and mobility of bladder noted along with
any fixation to contiguous structures
visible tumors resected by electrocautery
suspicious areas biopsied by cup biopsy forceps

12. NATURAL H/O AND SELECTION OF THE PATIENT :
1. STANDARD HISTOPATHOLOGICAL ASSESSMENT :
• Tumor recurrence and progression –two separate groups
• Progression –mets –greater biological risk
• Recurrence without progression –patient morbidity,
periodic re evaluation
repeat endoscopic ablation
intravesical chemotherapy
• Superficial or nonmuscle invasive –stage Tis,Ta or T1
• Invasive into muscle wall and beyond
• Mets –regional or distant

13. CANCER STAGE TREATMENT OPTIONS
Tis Complete TUR followed by intravesical BCG
Ta (single , low to moderate grade,not recurrent) Complete TUR
Ta (large, multiple , high grade , or recurrent) Complete TUR followed by intravesical chemo or
immunotherapy
T1 Complete TUR followed by intravesical chemo or
immunotherapy or radical cystectomy
T2-T4
(T3A,T3B and T3 –High grade )
Radical cystectomy
Neoadjuvant chemotherapy followed by radical
cystectomy
radical cystectomy followed by adjuvant
chemotherapy
Concomitant chemotherapy and irradiation
Any T, N+, M+ Systemic chemotherapy followed by selective
surgery or irradiation

14. •Presence of pelvic lymph node mets –most important prognostic
factor
•Grade increases –progression increases
•Recurrence –h/o disease ,grade ,number and size of the tumor
•T1,multiple ,large, high grade tumors –greater risk
2.MOLECULAR MARKERS:
•Tumor growth and mets –require angiogenesis
•Angiogenic stimulators –Fibroblastic growth factor and vascular
endothelial growth factor
•Angiogenic inhibitors –thrombospondin 1 and angiostatin
•Immunohistochemical quantification of angiogenesis –by measuring
microvessel density –prognostic indicator
•P53 –Tumor supressor gene –regulation of cell cycle
•DNA damage occurs –level of p53 ses –cell cycle arrest and repair
of DNA

15. •P53 mutated gene –abnormal protein product –allows damaged
DNA to continue the cell cycle
•Allows detection by immunohistochemically
•Increased risk –recurrence and decreased survival rate
•Rb gene alteration –high grade, high stage bladder cancers
3.TREATMENT SELECTION :
•Shown in the table
TREATMENT:
A. INTRAVESICAL CHEMOTHERAPY:
• Reduces recurrence and progression in pts where tumors
completely resected
• Following TUR –prophylactically to reduce tumor cell
implantation
• Weekly for 6 weeks

16. •Local toxicity –irritative voiding symptoms
•m/c used agents –mitomycin c
thiotepa
BCG
1. MITOMYCIN C:
• Antitumor,antibiotic, alkylating agent –inhibits DNA synthesis
• 40mg in 40cc of sterile water or saline once a week for 6 weeks
• After complete TUR
• Side effects : frequency ,urgency and dysuria
• Unique side effect : appearance of rash on the palms and genitalia

17. Use Timing Goal
Adjunctive At TUR Prevent implantation
prophylactic After complete TUR Prevent or delay recurrence or
progression
Therapeutic after incomplete TUR Cure residual disease
Delivery of intravesical immuno or chemotherapy
2.THIOTEPA:
•Alkylating agent
•Significant lower recurrence rates
•Cystitis –common
•Systemic absorption –leukopenia and thrombocytopenia –
myelosuppression
•

18. 3.BCG:
•Attenuated strain of mycobacterium bovis
•Mucosal ulceration and granuloma formation –common
•Therapeutically and prophylactically used
•Most effective –CIS
•Weekly for 6 weeks followed by 6 weeks where no BCG is given
•3 instillations once a week at 3 to 6 month intervals for 3 yrs
following TUR
•More effective than chemo –in preventing progression of superficial
cancers
•s/e : urgency, dysuria
•Hemorrhagic cystitis
•Prolonged high fever
symptomatic granulomatous prostatitis t/t with isoniazid and
evidence of systemic infection rifampicin

19. •BCG sepsis : high fever
chills
confusion
hypotension t/t with isoniazid ,rifampicin
respiratory failure and ethambutol
jaundice +
cycloserine or prednisolone
Increases survival rates
4.NEW INTRAVESICAL AGENTS:
•Low dose BCG with interferon –decrease recurrence
B.SURGERY:
1.TUR:
•Initial t/t –all bladder cancers
•Accurate estimate of tumor stage and grade

20. •Low grade , non invasive tumors –TUR
•Superficial disease but high grade –TUR followed by intravesical
therapy
•Follow up –necessary –because recurrence common –depending on
cancer grade , tumor stage and number of tumors
•3 months after resection –predictor of recurrence and progrssion
•Repeat cystoscopy at 1 year
•Recurrence pts –every 3 months –cystoscopy
2.PARTIAL CYSTECTOMY:
•Solitary , infiltrating (T1-3) localized along posterior lateral wall or
dome of bladder or cancers in diverticulum –candidates
•Preop –intravesical chemotherapy or limited dose irradiation at
time of surgery –minimize implantation

21. 3.RADICAL CYSTECTOMY :
•Gold standard –invasive bladder cancers
•Removal of anterior pelvic organs :
Men –bladder with surrounding fat and peritoneal attachments
prostate
seminal vesicles
Women –bladder with surrounding fat and peritoneal attachments
uterus
anterior vaginal vault
urethra
ovaries
•Recurrence –first 3 years
•Infiltration of prostatic stroma or prostatic urethra with cancer or
CIS –Urethral tumor involvement
•B/L pelvic lymph node involvement –usually performed

22. •Lymphadenectomy with radical cystectomy –also performed
C.RADIOTHERAPY:
•External beam irradiation (5000-7000 cGy) –over 5 to 8 week period
–deeply infiltrating bladder cancer pts
•Monotherapy –poor surgical candidates due to advanced age or
significant comorbid medical conditions
D.CHEMOTHERAPY:
•Cisplatin –most active agent
•Others –methotrexate
doxorubicin
vinblastine
cyclophosphamide
gemcitabine
5-fluorouracil

23. •Advanced bladder cancers –MVAC
•M –Methotrexate
•V –vinblastine
•A –adriamycin (doxorubicin)
•C –cisplatin
•Advantage of gemcitabine and cisplatin over MVAC –lower toxicity
and improved tolerability
E.COMBINATION THERAPY:
•Neoadjuvant chemo –preoperatively
•Decrease recurrence and bladder preservation cases
•Improve survival rates
•Locally advanced disease –increased risk of recurrence –adjuvant
chemotherapy
•Irradiation with chemotherapy –Improve survival rates,Decrease
recurrence and bladder preservation cases

24. •Invasive bladder cancer –Complete TUR +concomitant
chemotherapy and radiotherapy
•Cisplatin and gemcitabine –most radiosensitising agents
•Predictors of poor outcome after chemoradiation
–hydronephrosis at presentation
advanced clinical tumor stage
inability to complete entire t/t protocol
poor performance status