BLADDER CANCER

BLADDER CANCER - Margaret E.Thompson, MD
BASICS
DESCRIPTION
Primary malignant neoplasms arising in the urinary bladder
• Most common type is transitional cell carcinoma (90%)
• Other types include adenocarcinoma, small cell carcinoma, and squamous cell carcinoma.
• Rhabdomyosarcoma of the bladder may occur in children
GENERAL PREVENTION
Smoking cessation
EPIDEMIOLOGY
Incidence increases with age (median age at diagnosis = 73 years)
• More common in men than in women (4:1)
• More common in Whites than Asians or African Americans
Incidence
• 36.0 per 100,000 men per year (1)
• 9.1 per 100,000 women per year
Prevalence
As of January 1, 2002, 367,550 men and 131,649 women in the United States (1)
RISK FACTORS
• Smoking is the single greatest risk factor
• Other risk factors
- Occupational carcinogens in dye, rubber, paint, plastics, metal, and automotive exhaust
- Schistosomiasis in Mediterranean (squamous cell cancer)
- History of pelvic irradiation
- Chronic lower urinary tract infection
- Chronic indwelling urinary catheter
- Cyclophosphamide exposure
- High-fat diet
- Chronic low fluid intake
- Slight increase in risk with prostate cancer
Genetics
Hereditary transmission unlikely, though transitional cell carcinoma pathophysiology is related to oncogenes; in particular, p56
PATHOPHYSIOLOGY
• 70-80% is superficial (in lamina propria or mucosa):
- Usually highly differentiated with long survival
• Initial event seems to be activation of an oncogene on chromosome 9
• 20% of tumors are invasive (deeper than lamina propria) at presentation:
- Tend to be high grade with worse prognosis
ETIOLOGY
• See "Risk Factors"
• Activation of oncogene on chromosome 9
ASSOCIATED CONDITIONS
Cigarette smoking


DIAGNOSIS
PRE HOSPITAL
Diagnosis depends on biopsy results obtained by cystoscopy, which is often performed in ambulatory site or as outpatient surgery
SIGNS AND SYMPTOMS
• Hematuriagross or microscopic, usually painless
• May have urinary frequency, urgency, nocturia
• Abdominal or pelvic pain in advanced disease
History
• Hematuria (gross or microscopic) (85-90%)
• Urinary symptomsfrequency, urgency
• Exposures (see "Risk Factors")
Physical Exam
• Normal in early cases
• Pelvic or abdominal mass in advanced disease
• Wasting in systemic disease
TESTS
Urinalysis is the initial test in patients presenting with gross hematuria or urinary symptoms
Lab
• Macroscopic hematuria (55% sensitivity, PPV 0.22 for urologic cancer) (2)[A]
• Urine cytology 54% sensitivity over all, (lower in less-advanced tumors), 94% specific (3)[A]
• Other urine markers
- NMP22: 67% sensitive, 78% specific (3)[A]
- BTA stat: 70% sensitive, 75% specific (3)[A]
• Bottom line: None of the urine markers is sensitive enough to rule out bladder cancer on its own. Cytology is the most specific. (3)[A]
Imaging
Done for staging and evaluating extent of disease, but not for diagnosis itself
• IV push to look at upper tracts if there is suspicion of disease there
• For invasive disease, metastatic workup should include chest x-ray, liver function tests, alkaline phosphatase
• Bone scan should be performed if the patient has bone pain or if alkaline phosphatase is elevated (4)[B]
• Urologic CT scan (abdomen, pelvis, with and without contrast) or MRI 40-98% accurate, with MRI slightly more accurate (4)[B]: Recommended if metastasis is suspected
Diagnostic Procedures/Surgery
• Cystoscopy is the gold standard for diagnosis, but one study showed that 33% of patients had residual tumor after transurethral resection of superficial tumor (4)[B]
• Transurethral resection of the bladder tumor (TURBT) with bladder washings
- Sensitivity of cytology on bladder washings for carcinoma in situ is nearly 100%
ALERT
Any patient who smokes and presents with microscopic or gross hematuria, or irritative voiding symptoms such as urgency and frequency, should be evaluated by cystoscopy for the presence of a bladder neoplasm.
Pathological Findings
• Characterized as superficial or invasive
• 70-80% present as superficial lesion
• Superficial lesions
- Carcinoma-in-situ (CIS, Tis): Flat lesion, high grade
- TaNon-invasive papillary carcinoma (Ta)
- T1Extends into submucosa, lamina propria
• Invasive cancer
- T2Invasion into muscle
 pT2ainvasion into superficial muscle
 pT2binvasion into deep muscle
- T3Invasion into perivesical fat
 pT3amicroscopic
 pT3bmacroscopic
- T4invasion into adjacent organs
 aT4ainvades prostate, uterus, or vagina
 aT4binvades abdominal or pelvic wall
- N1-N3invades lymph nodes
- Mmetastasis to bone or soft tissue
DIFFERENTIAL DIAGNOSIS
Includes differential diagnosis for hematuria
• Other urinary tract neoplasms
• UTI
• Prostatism
• Bladder instability
• Interstitial cystitis
• Uroltihiasis
• Interstitial nephritis
• Papillary urothelial hyperplasia
TREATMENT
STABILIZATION
Generally, hematuria from bladder cancer is not significant enough to cause hemodynamic compromise.
GENERAL MEASURES
Radiotherapy
• In the United States, used for patients with muscle-invasive cancer who are not surgical candidates
• Treatment of choice for muscle-invasive cancer in some European and Canadian centers:
- 65-70 Gy over 6-7 weeks is standard
• Chemotherapy with cis-platin combined with radiotherapy may preserve bladder function
MEDICATION (DRUGS)
• Intravesical Bacillus Calmette-Guerin (BCG) after TURBT in high grade lesions has been shown to decrease recurrence in Ta or T1 tumors (5)[A]
- Common regimen is weekly for 6 weeks, then monthly for 6-12 months
• Intravesical mitomycin C also used
First Line
Chemotherapy is the first-line treatment for metastatic bladder cancer
• Methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is preferred regimen
SURGERY
• Diffuse carcinoma in situ is treated with intravesical therapy (see Medication)
• Superficial cancer
- TURBT sometimes followed by intravesical therapy
• Invasive cancer
- Radical cystectomy for invasive disease that is confined to the bladder more effective than radical radiotherapy. (6)[A] Urine is diverted via an ileal loop with ostomy or neobladder constructed with intestine.
- Neoadjuvant chemotherapy with cisplatin-methotrexate-vinblastine prior to surgery used by some centers
FOLLOW-UP
• Superficial cancers
- Urine cytology alone has not been shown to be sufficient for follow up
- Cystoscopy every 3 months for 18-24 months, every 6 months for the next 2 years, then annually (7)[C]
• Follow-up for invasive cancers is dependent on the approach to treatment
• Patients treated with BCG require life-long follow-up
DISPOSITION
Admission Criteria
Need for surgery or intensive therapy
Issues for Referral
Patients with microscopic or gross hematuria should be referred to a urologist for cystoscopy
PROGNOSIS
• Superficial bladder cancer
- BCG treatment prevents recurrence vs TURBT alone, difference 30%, NNT 3.3 (7)[A]
- BCG prevents progression vs TURBT alone, difference 8% (7)[A]
• Invasive cancer
- T2 diseaseradical cystectomy results in 60-75% 5-year survival
- T3 or T4 diseaseradical cystectomy results in 20-40% 5-year survival
- Neoadjuvant chemotherapy with cystectomy has led to varying degrees of increased survival.
- Radiation with chemotherapy has led to varying degrees of increased survival.
• Metastatic cancer
- MVAC resulted in mean survival of 12.5 months (8)[C]
COMPLICATIONS
• Superficial bladder cancer
- Local symptoms
 Dysuria, frequency, nocturia, pain, passing debris in urine
 Bacterial cystitis
 Perforation
- General symptoms
 Flu-like symptoms
 Systemic infection
• Invasive cancer
- Symptoms related to definitive treatment, including incontinence, bleeding
- Patients with neobladder at risk for azotemia and metabolic acidosis
PATIENT MONITORING
See "Follow-Up"
REFERENCES
1. National Cancer Institute. SEER Cancer fact sheet, Ries LAG, Eisner MP, Kosary CL, et al., eds. SEER Cancer Statistics Review, 1975-2002, National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2002. Accessed February 10, 2006.
2. Buntinx F, Wauters H. The diagnostic value of macroscopic haematuria in diagnosing urological cancers: A meta-analysis. Fam Pract. 1997;14: 63-68.
3. Glas AS, Roos D, Deutekom M, et al. Tumor markers in the diagnosis of primary bladder cancer. A systematic review. J Urol. 2003;169:1975-1982.
4. Kirkali Z, Chan T, Manoharan, M, et al. Bladder cancer: epidemiology, staging, and grading, and diagnosis. Urology. 2005;66(Suppl 6A):4-34.
5. Shelley MD, Court JB, Kynaston H, et al. Intravesical Bacillus Calmette-Guerin in Ta and T1 bladder cancer (Cochrane Review). In: The Cochrane Library, Issue 4, 2005. Chichester, UK: John Wiley and Sons, Ltd.
6. Shelley MD, Barber J, Wilt T, Mason MD. Surgery versus radiotherapy for muscle invasive bladder cancer (Cochrane Review). In: The Cochrane Library, Issue 4, 2005. Chichester, UK: John Wiley and Sons, Ltd.
7. Smith JA, Labasky RF, Montie JE, Rowland RG, Cockett, ATK, Fracchia JA. Report on the management of non-muscle invasive bladder cancer. American Urologic Association monograph. Baltimore, MD: American Urology Association, Inc. 1999.
8. Loehrer PJ, Einhorn LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study. J Clin Oncol 1992;10:1066.
9. U.S. Preventive Services Task Force. Screening for bladder cancer in adults: Recommendation statement. Rockville, MD: Agency for Healthcare Research and Quality; 2004.
MISCELLANEOUS
See also: Hematuria