Bladder Cancer

Epidemiology of Bladder CA

Accts for > 90% of UG tumors 4th most common CA in men, 9th 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 Conduit Diversion Flow 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 selfcathd. 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