A. Intravesical Chemotherapy: Immuno- or chemotherapeutic agents can be delivered directly into the bladder by a urethral catheter. They can be used to eradicate existing disease or to reduce the likelihood of recurrence in those who have undergone complete transurethral resection. Such therapy is more effective in the latter situation. Most agents are administered weekly for 6–12 weeks. The use of maintenance therapy after the initial induction regimen may be beneficial. Efficacy may be increased by prolonging contact time to 2 hours. Common agents include thiotepa, mitomycin, doxorubicin, and BCG, the latter being the most effective agent when compared with the others. Side effects of intravesical chemotherapy include irritative voiding symptoms and hemorrhagic cystitis. Systemic effects are rare. Patients who develop symptoms from BCG may require antituberculous therapy.
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B. Surgical Treatment: Although transurethral resection is the initial form of treatment for all bladder cancers as it is diagnostic, allows for proper staging, and will control superficial cancers, muscle infiltrating cancers will require more aggressive treatment. Partial cystectomy may be indicated in patients with solitary lesions and those with cancers in a bladder diverticulum. Radical cystectomy entails removal of the bladder, prostate, seminal vesicles, and surrounding fat and peritoneal attachments in men and in women also the uterus, cervix, urethra, anterior vaginal vault, and usually the ovaries. Bilateral pelvic lymph node dissection is performed simultaneously.
Urinary diversion can be performed using a conduit of small or large bowel. However, continent forms of diversion have been developed that avoid the necessity of an external appliance.
C. Radiotherapy: External beam radiotherapy delivered in fractions over a 6- to 8-week period is generally well tolerated, but approximately 10–15% of patients will develop bladder, bowel, or rectal complications. Unfortunately, local recurrence is common after radiotherapy (30–70%). Increasingly, radiotherapy is being combined with systemic chemotherapy in an effort to improve local and distant relapse rates.
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D. Chemotherapy: Fifteen percent of patients with newly diagnosed bladder cancer will present with metastatic disease, and 40% of those thought to have localized disease at the time of cystectomy or definitive radiotherapy will develop metastases usually within 2 years after the start of treatment. Cisplatin-based combination chemotherapy will result in partial or complete responses in 15–35% and 15–45% of patients, respectively.
Combination chemotherapy has been integrated into trials of surgery and radiotherapy. It has been used before each in an attempt to preserve the bladder and decrease recurrence rates. Alternatively, it has been employed postoperatively in patients who have undergone cystectomy and have been found to be at high risk of recurrence. In current practice, adjuvant chemotherapy when indicated—ie, when the primary tumor invades perivesical fat or adjacent organs or when lymph nodes are found to have metastatic disease—is being offered mainly to patients being treated with radical cystectomy. It is used less often for patients with unresectable disease (extension to pelvic side wall).
T: Primary tumor
Tx Cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ (CIS)
Ta Noninvasive papillary carcinoma
T1 Invasion into lamina propria
T2 Invasion into superficial layer of muscularis propria
T3a Invasion into deep layer of muscularis propria
T3b Invasion through serosa into perivesical fat
T4a Invasion into adjacent organs
T4b Invasion into pelvic sidewall
N: Regional lymph nodes
Nx Cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node £ 2 cm
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N2 Metastasis in a single lymph node > 2 cm and < 5 cm or multiple
nodes none > 5 cm
N3 Metastasis in lymph node > 5 cm
M: Distant metastasis
Mx Cannot be assessed
M0 No distant metastasis
M1 Distant metastasis present
The natural history of bladder cancer is based on two separate but related processes: tumor recurrence and progression to higher stage disease. Both are related to tumor grade and stage. At initial presentation, approximately 50–80% of bladder cancers will be superficial: Ta, Tis, T1. Lymph node metastases and progression are uncommon in such patients when they are properly treated, and survival is excellent at 81%. Patients with superficial cancers (Ta, T1) are treated with complete transurethral resection and the selective use of intravesical chemotherapy. The latter is used to prevent or delay recurrence. Patients who present with large, high-grade, recurrent Ta lesions, T1 cancers, and those with carcinoma in situ are good candidates for intravesical chemotherapy. Patients with more invasive (T2, T3) but still localized cancers are at risk of both nodal metastases and progression, and they require more aggressive surgery, irradiation, or the combination of chemotherapy and selective surgery or irradiation due to the much higher risk of progression compared to patients with lower-stage lesions. Patients with evidence of lymph node or distant metastases should undergo systemic chemotherapy initially.
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Ninety-eight percent of primary bladder cancers are epithelial malignancies, with the majority being transitional cell carcinomas (90%). These latter cancers most often appear as papillary growths, but higher-grade lesions are often sessile and ulcerated. Grading is based on histologic architecture: size, pleomorphism, mitotic rate, and hyperchromatism. The frequency of recurrence and progression is strongly correlated with grade. Whereas progression may be noted in few grade I cancers (19–37%), it is common with poorly differentiated lesions (33–67%). Carcinoma in situ is recognizable as a flat, nonpapillary, anaplastic epithelium and may occur focally or diffusely, but it is most often found in association with papillary bladder cancers. Its presence identifies a patient at increased risk of recurrence and progression.
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Adenocarcinomas and squamous cell cancers account for approximately 2% and 7% (respectively) of all bladder cancers detected in the USA. The latter is often associated with schistosomiasis, vesical calculi, or chronic catheter use.
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Bladder cancer staging is based on the extent of bladder wall penetration and the presence of either regional or distant metastases. The TNM classification of the American Joint Cancer Committee for bladder cancer is shown in Table 23–11.
Bladder cancer is the second most common urologic cancer. Bladder cancer occurs more commonly in men than women (2.7:1), and the mean age at diagnosis is 65 years. Cigarette smoking and exposure to industrial dyes or solvents are risk factors for the disease and account for approximately 60% and 15% of new cases, respectively.
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Clinical Findings
A. Symptoms and Signs: Hematuria – gross or microscopic, chronic or intermittent—is the presenting symptom in 85–90% of patients with bladder cancer. Irritative voiding symptoms (urinary frequency and urgency) will occur in a small percentage of patients as a result of the location or size of the cancer. Most patients with bladder cancer will fail to have signs of the disease because of its superficial nature. Masses detected on bimanual examination may be present in patients with large-volume or deeply infiltrating cancers. Hepatomegaly or supraclavicular lymphadenopathy may be present in patients with metastatic disease, and lymphedema of the lower extremities may be present as a result of locally advanced cancers or metastases to pelvic lymph nodes.
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B. Laboratory Findings: Urinalysis will reveal hematuria in the majority of cases. On occasion, it may be accompanied by pyuria. Azotemia may be present in a small number of cases associated with ureteral obstruction. Anemia may occasionally be due to chronic blood loss or to bone marrow metastases. Exfoliated cells from normal and abnormal urothelium can be readily detected in voided urine specimens. Cytology may be useful in detecting the disease at the time of initial presentation or to detect recurrence. Cytology is very sensitive in detecting cancers of higher grade and stage (80–90%) but less so in detecting superficial or well-differentiated lesions (50%). Sensitivity of detection using exfoliated cells may be enhanced by flow cytometry.
C. Imaging: Bladder cancers may be detected using intravenous urography, ultrasound, CT, or MRI where filling defects within the bladder are noted. However, the presence of cancer is confirmed by cystoscopy and biopsy, so imaging is useful primarily for evaluating the upper urinary tract and in staging the more advanced lesions.
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D. Cystourethroscopy and Biopsy: The diagnosis and staging of bladder cancers is made by cystoscopy and transurethral resection. If cystoscopy—performed usually under local anesthesia—confirms the presence of bladder cancer, the patient is scheduled for transurethral resection under general or regional anesthesia. A careful bimanual examination is performed initially and at the end of the procedure, noting the size, position, and degree of fixation of a mass, if present. Any suspicious lesions are resected using electrocautery. Resection is carried down to the muscular elements of the bladder wall so as to allow complete staging. Random bladder and, on occasion, prostatic urethral biopsies are performed to detect occult disease elsewhere in the bladder and, therefore, identify patients at high risk of recurrence and progression.