INCIDENCE AND EPIDEMIOLOGY
Annual incidence in the United States is about 74,000 cases with 16,000 deaths. Median age is 65 years. Smoking accounts for 50% of the risk. Exposure to polycyclic aromatic hydrocarbons increases the risk, especially in slow acetylators. Risk is increased in chimney sweeps, dry cleaners, and those involved in aluminum manufacturing. Chronic cyclophosphamide exposure increases risk ninefold. Schistosoma haematobium infection also increases risk, especially of squamous histology.
Lesions involving chromosome 9q are an early event. Deletions in 17p (p53), 18q (the DCC locus), 13q (RB), 3p, and 5q are characteristic of invasive lesions. Overexpression of epidermal growth factor receptors and HER2/neu receptors is common.
Over 90% of tumors are derived from transitional epithelium; 3% are squamous, 2% are adenocarcinomas, and <1% are neuroendocrine small cell tumors. Field effects are seen that place all sites lined by transitional epithelium at risk, including the renal pelvis, ureter, bladder, and proximal two-thirds of the urethra; 90% of tumors are in the bladder, 8% in the renal pelvis, and 2% in the ureter or urethra. Histologic grade influences survival. Lesion recurrence is influenced by size, number, and growth pattern of the primary tumor.
Hematuria is the initial sign in 80–90%; however, cystitis is a more common cause of hematuria (22% of all hematuria) than is bladder cancer (15%). Pts are initially staged and treated by endoscopy. Superficial tumors are removed at endoscopy; muscle invasion requires more extensive surgery.
TREATMENT: BLADDER CANCER
Management is based on extent of disease: superficial, invasive, or metastatic. Frequency of presentation is 75% superficial, 20% invasive, and 5% metastatic. Superficial lesions are resected at endoscopy. Although complete resection is possible in 80%, 30–80% of cases recur; grade and stage progression occur in 30%. Intravesical instillation of bacille Calmette-Guérin (BCG) reduces the risk of recurrence by 40–45%. Recurrence is monitored every 3 months.
The standard management of muscle-invasive disease is radical cystectomy. 5-year survival is 70% for those without invasion of perivesicular fat or lymph nodes, 50% for those with invasion of fat but not lymph nodes, 35% for those with one node involved, and 10% for those with six or more involved nodes. Pts who cannot withstand radical surgery may have 30–35% 5-year survival with 5000- to 7000-cGy external beam radiation therapy. Bladder sparing may be possible in up to 45% of pts with two cycles of chemotherapy with CMV (methotrexate, 30 mg/m2 days 1 and 8, vinblastine, 4 mg/m2 days 1 and 8, cisplatin, 100 mg/m2 day 2, q21d) followed by 4000-cGy radiation therapy given concurrently with cisplatin.
Metastatic disease is treated with combination chemotherapy. Useful regimens include CMV (see above), M-VAC (methotrexate, 30 mg/m2 days 1, 15, 22; vinblastine, 3 mg/m2 days 2, 15, 22; doxorubicin, 30 mg/m2 day 2; cisplatin, 70 mg/m2 day 2; q28d) or cisplatin (70 mg/m2 day 2) plus gemcitabine (1000 mg/m2 days 1, 8, 15 of a 28-day cycle) or carboplatin plus paclitaxel. About 70% of pts respond to treatment, and 20% have a complete response; 10–15% have long-term disease-free survival.