BLADDER CANCER

Dr Alex Mogere
Consultant Physician
Introduction
• Most common site of cancer in the urinary tract
• X2.7 > male
• White > black
• In men-4th commonest cause of Cancer
• Women-8th most common cause of Ca
• Disease of elderly: 67-70yrs
• Younger pts have better prognosis
• Transitional cell epithelium lines the urinary tract from the renal pelvis to
the ureter, urinary bladder, and the proximal two-thirds of the urethra.
Cancers can occur at any point.
Introduction
• 90% of malignancies develop in the bladder, 8% in the renal pelvis,
and 2% in the ureter or urethra
• Once diagnosed, urothelial tumors exhibit polychronotropism, which
is the tendency to recur over time in new locations in the urothelial
tract
Ct.Bladder structure
• Serous- from peritoneum
• Muscular- detrusor and trigone
• Mucosa and submucosa
• urothelium- multilayered transitional cell epithelium(3-7 layers thick)
Risk factors
• Typically not an inherited disease
• Chemical exposure: aniline dyes, 2-naphthlamine,exposure to
petroleum, textiles, paint, dyes
• Smoking: greatest risk factor; black tobacco, unfiltered cigarettes,
both current and prev hx are risk factors(cessation 30-60% reduction)
• Exposure to Schistosoma haematobium, a parasite found in many
developing countries, is associated with an increase in both squamous
and transitional cell carcinomas of the bladder.
Cont. risk factor
• Others : artificial sweeteners, coffee, tea, cyclophosphamide(very
high risk), ISS, analgesics abuse
• Diet rich in Vit A & C, carotene – protective
• Chronic bladder inflammation: recurrent cystitis, calculi
• Irradiation
• Exposure to arsenic(found in soil and rocks)
Pathology
• Clinical subtypes grouped in 3 categories:
75% are superficial,
20% invade muscle, and
5% are metastatic at presentation
• Tumors are also rated by grade:
Low-grade (highly differentiated) tumors rarely progress to a higher stage,
whereas high-grade tumors do.
• More than 95% of urothelial tumors in the US are transitional cell in origin.
• Pure squamous cancers with keratinization constitute 3%, adenocarcinomas
2%, and small cell tumors (often with paraneoplastic syndromes) <1%.
Cont. pathology
• Adenocarcinomas develop primarily in the urachal remnant in the
dome of the bladder or in the periurethral tissues
• Of the transitional cell tumors, low-grade papillary lesions that grow
on a central stalk are most common.
• Carcinoma in situ (CIS) is a high-grade tumor that is considered a
precursor of the more lethal muscle-invasive disease
Preneoplastic abnormalities
• Cystitis cystica
• Cystitis grandularis
• Inverted paipilloma
• Nephrogenic adenoma
• Squamopus metaplasia
• Atypcal hyperplasia
Types of bladder tumors
Carcinoma in situ
• Proliferation confined to epithelium of mucosa
• Potential for invasiveness considerable
• In 4 yrs 80% of pts develop invasive Ca
• Urine cytopathology- positive in 80-90% of cases
• Cystoscopy- velvety appearance/erythematous mucosa
SCC
• 5-10% of bladder tumors
• There are 2 types-bilharzial/non-bilharzial
• Bilharzial bladder cancer :
Chronic infection with SH
Exophytic , nodular , fungating lesion
Well differentiated
Incidence of lymph node, mets- low
• Non-bilharzial bladder Ca:
Chronic irritation(calculi, indwelling catheters)
Keratinized cells- squamous pearls
Adenocarcinoma
• Primary vesical adenocarcinoma
• Urachal carcinoma
• Metastatic adenocarcinoma- from rectum, stomach,
endometrium,breast, prostate, ovary
TNM Staging
Clinical presentation
• The bladder is the most common source of gross hematuria (40%),
but benign cystitis (22%) is a more common cause than bladder
cancer (15%)
• Microscopic hematuria is more commonly of prostate origin (25%)
• only 2% of bladder cancers produce microscopic hematuria.
• irritative symptoms are the next most common presentation
• Ureteral obstruction may cause flank pain
• Advanced malignancy: suprapubic mass, wt loss, bone pain
Spread
• Direct spread-local invasion
• Metastatic spread
• Lymphatic spread
• Vascular spread
• Implantation-denuded urothelium, wounds etc
TNM Staging
Modalities for staging (local extent; T stage)
• Excretory urography
• Transurethral ultrasonography
• Transurethral resection
• Select mucosal biopsy
• Cytology
• Prostate fossa biopsy
• EUA
• CT SCAN/MRI
Modalities for staging (regional extent;N
stage)
• CT
• MRI
• Lymphangiography
• Laparascopy
• PET scanning
Systemic extent; M stage
• Pulmonary: CXR, CT/PET scan,
• Bone: bone scan,bone survey, MRI
• Liver- u/s, CT/NRI/PET scan
Evaluation
• Once hematuria is documented, a urinary cytology, visualization of the
urothelial tract by computed tomography (CT) or magnetic resonance
urogram or intravenous pyelogram, and cystoscopy are recommended if no
other etiology is found
• Cystoscopy is the gold standard
• Screening asymptomatic individuals for hematuria increases the diagnosis of
tumors at an early stage but has not been shown to prolong life
• The endoscopic evaluation includes an examination under anesthesia to
determine whether a palpable mass is present.
• A flexible endoscope is inserted into the bladder, and bladder barbotage for
cytology is performed.
Ct . evaluation
• Visual inspection includes mapping the location, size, and number of
lesions, as well as a description of the growth pattern (solid vs papillary).
• All visible tumors should be resected, and a sample of the muscle
underlying the tumor should be obtained to assess the depth of
invasion.
• Normal-appearing areas are biopsied at random to ensure no CIS is
present.
• Selective catheterization and visualization of the upper tracts should be
performed if the cytology is positive and no disease is visible in the
bladder.
Ct. evaluation
• Ultrasonography, CT, and/or magnetic resonance imaging (MRI) are
used to determine whether a tumor extends to perivesical fat (T3)
and to document nodal spread.
• Distant metastases are assessed by CT of the chest and abdomen,
MRI, or radionuclide imaging of the skeleton.
• Diagnostic tumor markers
Tx of Bladder Cancer
• Management depends on whether the tumor invades muscle and
whether it has spread to the regional lymph nodes and beyond.
Tx. of non muscle invasive disease
• At a minimum, the management is complete endoscopic resection
with or without intravesical therapy.
• The decision to recommend intravesical therapy depends on:
the histologic subtype,
number of lesions,
depth of invasion,
presence or absence of CIS, and
antecedent history.
Ct . Tx. of non muscle invasive disease
• Intravesical treatments are advised for:
patients with diffuse CIS,
recurrent disease,
>40% involvement of the bladder surface by tumor, or
T1 disease
• The standard therapy, based on randomized comparisons, is Bacillus
Calmette-Guérin (BCG) in six weekly instillations, often followed by
maintenance administrations for ≥1 year.
• Other agents with activity include mitomycin C, interferon, and
gemcitabine.
S/es of intravesical tx(depends on drug)
dysuria,
urinary frequency,
myelosuppression
contact dermatitis.
Contraindications to BCG use
• Immuno suppression
• Immediately after TURBT(transurethral resection of bladder tumor)
• Allergic rxn
• Traumatic catheterization
• Gross hematuria
Follow up
• Following the endoscopic resection, patients are monitored for
recurrence at 3-month intervals during the first year
• Persistent disease in the bladder and new tumors are treated with a
second course of BCG or intravesical chemotherapy with valrubicin or
gemcitabine.
Tx muscle invasive disease
• The Tx of a tumor that has invaded muscle can be separated into
control of the primary tumor and systemic chemotherapy to treat
micrometastatic disease
• Radical cystectomy is the standard Tx, although in selected cases, a
bladder-sparing approach is used.
• This approach includes complete endoscopic resection; partial
cystectomy; or a combination of resection, systemic chemotherapy,
and external beam radiation therapy
Indications for cystectomy
• muscle-invading tumors not suitable for segmental resection;
• non–muscle-invasive tumors unsuitable for conservative Mx (e.g., due
to multicentric and frequent recurrences resistant to intravesical
instillations);
• high-grade T1 tumors especially if associated with CIS; and
• bladder symptoms (e.g., frequency or hemorrhage) that impair
quality of life
• Persistent Cis
• Recurrence with invasion of lamina propria
Invasive bladder Cancer
• Diagnosis of muscle invasion(T2-T3)
• Metastatic disease should be excluded
• Aggressive therapy: bladder preservation/reconstruction
• Radical cystectomy – gold std
• TUR- small tumors with superficial muscle invasion
Radical cystoprostatectomy: indications
• Radical cystoprostatectomy in male and anterior exenteration in
female coupled with en bloc pelvic lymphadenectomy, remain the
standard surgical tx in the absence of metastatic disease
Radical cystectomy: indications
• Primary adenocarcinomas
• Cis
• SCC with /without schistosomiasis
• Sarcoma of the bladder
• Superficial papillary carcinoma
• Invasive carcinoma
Tx of metastatic disease
• The primary goal of metastatic disease tx is to achieve complete
remission with chemotherapy alone or with a combined modality
approach of chemotherapy followed by surgical resection of residual
disease.
• For most pts, treatment is palliative, aimed at delaying or relieving
cancer-related symptoms, because few patients experience durable
complete remissions.
Chemotherapy
• A number of chemotherapeutic drugs have activity as single agents;
cisplatin, paclitaxel, and gemcitabine are considered most active.
• Std therapy consists of two-, three-, or four-drug combinations
• Overall response rates of >50% have been reported using
combinations such as :
methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC);
gemcitabine and cisplatin (GC); or
gemcitabine, paclitaxel, and cisplatin (GPC).
•
Ct.chemotx
• At present, GC is used more commonly than MVAC based on the
results of a comparative trial of MVAC versus GC that showed less
neutropenia and fever and less mucositis for the GC regimen with
similar response rates and median overall survival.
Summary (mx of bladder Ca)
Prevention of Ca bladder
• Urine acidification
• Vitamins A,B6, C,E
• Avoid high fat/cholesterol diet
• More fluids
THANK YOU!