Bladder Cancer

Epidemiology of Bladder CA
Accts for > 90% of UG tumors

4
th
most common CA in men, 9
th
in women

Annual New Cases = 68,810 (51,230 in M & 17,580 in F)
M:F = 3:1, similar w/in all racial groups

Annual Deaths = 14,100 (7,750 in M & 4,150 in F)

Caucasians ~ 2x > African Americans > Hispanics & Asians

Median age at dx = 70. Rarely dxd before age 40.

Risk Factors for Bladder CA
Age, Gender, Race

Cigarette smoking (2-4x higher relative risk)

Exposures
Occupational - Polycyclic aromatic hydrocarbons, benzidine, benzene,
exhaust from combustion gases, arylamines
Al
+3
workers; dry cleaners; manufacturers of preservatives,
polychlorinated biphenyls, dye, rubber, & leather; pesticide applicators;
painters; truck drivers; hairdressers; printers; machinists
Cyclophosphamide, Ifosfamide ( 9 fold incd risk)
Pelvic radiation txs
Arsenic (eg, in drinking H2O)
Risk Factors for Bladder CA
Infections
Schistosoma haematobium (N Africa) Incd risk for
squamous & transitional cell CAR
Chronic UTIs, chronic bladder stones, indwelling Foleys incd
risk for squamous cell CAR

Other
Prior h/o bladder CA
Low fluid intake (incd exposure to carcinogens via decd bladder
emptying)
Genetics (eg, Retinoblastoma gene)
Bladder birth defects (eg, persistent urachus) incd risk for
adenoCAR
Pathology of Bladder CA
Transitional cell CAR (> 95%)
Papillary (70%) Grow toward the hollow part of the
bladder w/o invading deeper tissues. Often non-invasive.
Flat Do not grow toward the hollow part of the bladder.
Can be non-invasive or invasive depending on depth of
invasion

Squamous cell (keratinizing) CAR (1-3%) Generally invasive.

AdenoCAR (1-2%) Generally invasive.

Small cell CAR (< 1%)

Mixed-histology (predominantly transitional cell w/ areas of
other elements) are also common.
Clinical Manifestations of Bladder CA
Hematuria (80-90%) Generally painless and gross
hematuria
However, 20% can have only microscopic hematuria

Other urinary Sxs
Frequency, urgency, nocturia d/t irritative Sxs or decd bladder
capacity

Pain (less common & often reflects tumor location)
Lower abdominal pain Bladder mass
Rectal discomfort & perineal pain Invasion of prostate or
pelvis.
Flank pain - Obstruction of ureters
Dx of Bladder CA
Screening of aSxc pts not recommended

Pts w/ hematuria, especially if > 40 yoa
Urinary Cytology
Cystoscopy, regardless of cytology results
(mainstay of dx)
Transurethral resection of all visible tumors to
determine histology & depth of invasion
Biopsies of erythematous (& possibly normal)
areas to assess for CIS
Dx of Bladder CA
Pts w/ (+) cytology but no apparent bladder tumors
and/or (-) biopsies
Intravenous peylogram or CT urogram to evaluate for upper
urinary tract dz

Imaging
Generally only if (+) cystoscopy
U/S, CT, or MRI - Can help determine extent of tumor spread
(eg, into perivsesical fat, prostate or vagina, LNs)
CT chest / abdomen, MRI, radionuclide imaging of skeleton to
assess for distant mets
Tx & Prognosis of Bladder CA
Superficial Dz
~ 50% have recurrences, w/ 5-30% of these progressing
to a more advanced stage

Requires at least complete endoscopic resection +/-
intravesical therapy

Surveillance via cystoscopy & urine cytology
Q3 mos x 1 yr, Q4 mos x 1yr, Q6 mos x 1 yr

Periodic surveillance of upper GU tracts

Tx for persistent dz = repeat BCG or cystectomy


Tx & Prognosis of Bladder CA
Intravesical Therapy
Indications
Adjuvant tx w/ resection to prevent recurrence
Eliminate dz that cannot be controlled by endoscopic resection alone
(less common)
Recurrent dz, > 40% involvement of bladder surface, diffuse CIS, T1 dz
Generally not needed for solitary papillary lesions

Agents
Std agent -- BCG
Generally 6 weekly txs then monthly maintenance x 1-3 yrs
Toxicities = Bladder irritability / spasm, hematuria, dysuria, & rarely
systemic TB
Other agents Mitomycin-C, Interferon, Gemcitabine

Tx & Prognosis of Bladder CA
Muscle-Invasive Dz
Generally radical cystectomy & pelvic lymphadenectomy
unless significant metastatic dz
Removal of bladder & pelvic LNs w/ creation of a conduit or
reservoir for urinary flow.
+ Removal of prostate, seminal vesicles, & proximal urethra in
males. Generally impotence.
+ Removal of urethra, uterus, fallopian tubes, ovaries, anterior
vaginal wall, & surrounding fascia in females.
5-yr dz-free survival in 75-80% w/ organ-confined dz; ~ 50%
w/ tumors extending into the perivesical tissues, & in ~ 33% w/
mets to regional LNs.
Tx & Prognosis of Bladder CA
Muscle-Invasive Dz
Neo-adjuvant chemo x 12 wks prior to cystectomy
Incd 5-yr dz-free survival
MVAC (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) 3
cycles q 28 days

Concomitant Chemo & Radiation
For those w/ a solitary early-stage lesion and no hydronephrosis
Generally Cisplatin
5-yr dz-free survival rate of 50%,
Tx & Prognosis of Bladder CA
Muscle-Invasive Dz
Sometimes bladder sparing approach is used
(~ 5-10% are candidates)
Complete endoscopic resection; partial
cystectomy; or combination of resection, chemo,
and radiation
Considered when dz is limited to the bladder
dome, 2 cm can be achieved, no CIS in other
sites, & bladder capacity adequate after tumor
removal.

Tx & Prognosis of Bladder CA
Muscle-Invasive Dz Mgmt of Urine
Flow
Conduit Diversion
Urine is drained from the ureters to a loop of small bowel anastomosed to the
abdominal skin surface. It is then collected in an external appliance. Currently
uncommonly used.

Continent Cutaneous Reservoir
Created from a detubularized segment of bowel attached to the abdominal wall w/
a continent stoma that can be regularly self-cathd.
Continence in 6585% of men at night and 8590% of men during the day.

Orthotopic Neobladder
Low-pressure reservoirs anastomosed to the urethra more natural drainage, as
pts can void via the urethra.
CIs = Renal insuff, inability to self-catheterize, or an exophytic tumor or CIS in the
urethra.
Tx & Prognosis of Bladder CA
Metastatic Dz
2 Main Regimens (Gemcitabine + Cisplatin OR
MVAC)
6 cycles over 6 mos
GC is often better tolerated.
Both 5 yr survival rate of ~ 15% (20-33% if good
performance status and mets confined to LNs), w/
median survival of ~ 14 mos.
References
Harrisons Internal Medicine
Cecil Textbook of Medicine
Cancer: Principles & Practice of Oncology
National Cancer Institute website
American Cancer Society website