Bladder cancer is the second most common urologic cancer in adults. There are 67,000 new cases of bladder cancer each year in the United States.
Bladder cancer tends to occur most commonly in individuals over the age of 60 and is about 2 to 3 times more common in men than in women. Cigarette smoking and exposure to certain industrial chemicals (derivatives of compounds called arylamines and petrochemicals) are strongly associated with the development of bladder cancer.
Transitional cell carcinoma, also known as urothelial carcinoma, is the most common type of bladder cancer. Transitional cell bladder cancer may present in several different forms, including:
- Carcinoma in situ (CIS)
- Papillary carcinoma
- Sessile carcinoma
The depth of invasion, involvement of the bladder muscle and invasion into the lymphovascular spaces determine the risk, prognosis and treatment. Bladder cancer can be classified into two broad categories – non-muscle invasive and muscle invasive urothelial carcinoma.
Paul L. Crispen, MD
Pete and Carolyn Newsome Urologic Oncology Professorship
Associate Chair of Clinical Affairs
Department of Urology
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Padraic O’Malley, MSc, MD, FRCSC
Department of Urology
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Non-muscle Invasive Bladder Cancer
At the initial diagnosis, approximately 70% of patients with TCC have non-muscle invasive papillary cancers, but 50-70% of these patients have a recurrence within 5 years of treatment. Ten to twenty percent of superficial lesions progress to deep muscle invasive disease. Papillary tumors respond well to conservative treatment and are easily removed endoscopically (through a camera without a surgical incision). The rate of recurrence is approximately 70%; therefore additional treatment to prevent recurrence is usually prescribed in the form of intra-vesical therapy (placed directly into the bladder) and follow-up examinations are important. CIS tends to cause symptoms more frequently and may signal biologically aggressive disease. The risk of progression is 4-8% with some patients having a more rapid progression than papillary tumors. The overall 5-year survival for patients with non-muscle invasive and localized bladder cancer is greater than 92%.
Muscle-Invasive and Advanced Bladder Cancer
Between 20 and 25% of new cases of bladder cancer are muscle-invasive. Muscle-invasive bladder cancer is more aggressive than non-invasive disease, and approximately 50% of patients with muscle invasive disease will experience distant recurrence following therapy. Survival depends on disease stage and treatment; for organ-confined disease treated with surgery and in cases responsive to chemotherapy before cystectomy, 5-year survival is 85%. Common sites of metastasis include regional lymph nodes, bone, liver and lung. Survival decreases with more advanced disease. Five-year survival is approximately 50% in regionally advanced (lymph node positive) bladder cancer and <10% in the presence of distant metastases.
Signs & Symptoms
Irritative Urination Symptoms
- Incomplete emptying
For the majority of people, the first symptom of bladder cancer is blood in the urine called hematuria. Hematuria is either gross (viewable with the naked eye) or microscopic.
Irritative urination symptoms may also be associated with bladder cancer and include pain and burning on urination, frequency, and incomplete emptying of the bladder.
- Intravenous pyleogram (IVP)
- Transurethral resection (TUR)
- Urine testing/cytology
After taking a detailed medical history, the urologist will examine a urine specimen and check for evidence of blood and signs of infection.
The gold standard for the evaluation of the lower urinary tract is direct visual examination with a specialized instrument call a cystoscope. A cystoscope is a small camera inserted into the bladder. The purpose of routine outpatient cystoscopy is to evaluate the lining of the bladder and the urethra, the channel where urine passes out of the bladder and then exits the body. If abnormalities such as tumors or patches of abnormal-appearing tissue are discovered during cystoscopy, a biopsy or a sample of tissue may be taken at that time to determine the presence of cancer.
Because transitional cell carcinoma can also occur in the lining of the ureters and kidneys, routine surveillance of the upper tracks is also important following a diagnosis of bladder cancer. Several tests can be used to evaluate the upper tracks, including IVP and CT scan. An IVP is a conventional x-ray test using dye to examine the kidneys and ureters, tubes that transport urine from the kidneys to the bladder. This x-ray will look at the collecting system of the kidneys to determine the presence of an abnormality. A CT scan (Computed Axial Tomographic Scanning) and an MRI (Magnetic Resonance Imaging) are two tests which may be ordered in addition to the IVP to give the urologist further information needed.
Urine specimens will also be examined for abnormal cells. High grade tumors readily shed tumor cells into the voided urine allowing for pathologic examination of the urine specimen (cytology) for the presence of tumor cells.
Staging for Bladder Cancer
Clinical staging is performed with transurethral resection (TUR), CT scan, and exam under anesthesia (EUA). EUA allows the surgeon to manually assess the bladder after TUR for the presence of tumor.
Prognosis of bladder cancer is directly linked to the stage of the bladder cancer. Staging is a process that demonstrates how far the cancer has spread. The treatment and prognosis or outlook for bladder cancer will depend significantly on its stage.
TNM SYSTEM (TNM System stands for Tumor, Lymph Nodes, and Metastasis)
|T0||No primary bladder tumor present|
|Tis||Carcinoma in situ|
|Ta||Noninvasive papillary carcinoma|
|T1||Tumor invades supepithelial connective tissue|
|T2||Tumor confined to the bladder muscle|
|T2a||Tumor invades superficial muscle (inner half)|
|T2b||Tumor invades deep muscle (outer half)|
|T3||Tumor extends through the muscle (extravesical extension)|
|T3a||Microscopic extravesical invasion|
|T3b||Macroscopic extravesical invasion|
|T4||Tumor invades prostate, uterus, vagina, pelvic wall, abdominal wall|
|T4a||Tumor invades prostate, uterus, or vagina|
|T4b||Tumor invades pelvic wall or abdominal wall|
|N0||No regional lymph node metastasis|
|N1||Metastasis in a single node < 2 cm|
|N2||Metastasis in a single or multiple node 2-5 cm|
|N3||Metastasis in a single or multiple node > 5cm|
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Non-Invasive Bladder Cancer Treatment Options
The majority of bladder cancers arise from the lining of the bladder (non-invasive tumors). Treatment for non-muscle-invasive bladder cancer can include:
Cystoscopy with cautery destruction of the tumor
- Most modern cystoscopes are equipped with channels that permit small instruments to be passed into the bladder for the purpose of removing tissue, stopping bleeding with a special electrical device called an electro cautery or even performing laser treatment. If the bladder cancer is small enough this cautery may be used to remove the cancer.
Intra-vesical drug therapy
- Intra-vesical therapy is the use of one of several different types of medical therapies placed directly into the bladder through a urethral catheter. Therapies consist of drugs placed in the bladder in an attempt to minimize the risk of tumor recurrence and progression. These drugs come from a wide variety of sources. About 50-68% of patients with superficial bladder cancer have a very good response to intra-vesical therapy. The most commonly used intra-vesical is Bacille Calmette-Guerin (BCG), which is administered once a week for 6 straight weeks. BCG is a weaken tuberculosis (TB) bacterium. Maintenance therapy (repeated therapy on a regular basis) with BCG or another drug administered intermittently following initial diagnosis and treatment of superficial bladder tumor decreases the likelihood of recurrence.
Transurethral Resection (TUR)
- A transurethral resection is a procedure performed through the cystoscope whereby the tumor is resected without making a visible incision on the body. A small T.V. camera is inserted into the bladder to visualize the bladder. The entire removal of a bladder tumor can be accomplished through this operative cystoscope.Drug therapy after TUR is commonly prescribed for patients with tumors that are large, multiple or high-grade.The biopsy specimen or TUR specimen is sent to the pathologist who will evaluate the specimen for the presence, extent, and aggressiveness of cancerous cells. Surveillance is required after diagnosis for bladder cancer. Patients are generally monitored every 3 months for the first year or two, then every 6 months for a year or two, and once a year thereafter with a cystoscopy and a urine test for cancer (called urine cytology).
Invasive Bladder Cancer Treatment Options
Invasive bladder cancer is cancer that has invaded into the bladder wall or outside the bladder. Invasive bladder cancer treatment options are drastically different than those for superficial bladder cancer. Treatment options include:
- Cystectomy with urinary diversion – In men, the bladder and prostate are identified and dissected and removed. In women, the bladder, uterus, fallopian tubes, ovaries and anterior portion of the vagina are identified and dissected and removed. Surrounding lymph nodes are removed to assess the extent or spread of the cancer. Next, one of several reconstruction options are available to replace the removed bladder
Chemotherapy – Chemotherapy is a systemic treatment (i.e., drug that is dispersed throughout the entire body) that is designed to kill cancer cells. Typically, it is administered intravenously (through a vein). The chemotherapy may be administered before surgery (neoadjuvant therapy), after surgery (adjuvant therapy) or in the setting of advanced disease. On the other hand in patients with non-invasive
bladder cancer, chemotherapy may be infused into the bladder through the urethra (called intravesical chemotherapy) in hopes of reducing recurrence and progression of disease.
- Radiation therapy with chemotherapy – Radiation uses high-energy x-rays to destroy cancer cells. The addition of systemic chemotherapy renders cancer cells more susceptible to the killing effects of radiation. Radiation therapy is also used to relieve symptoms (called palliative treatment) of advanced bladder.