Bladder cancer affects over 52,000 men and women in the United States on an annual basis, and more than 12,000 people die each year from this disease. It is the fourth most common cancer in men in this country and the eighth most common in women.
Bladder cancer starts in the bladder's inside lining. Approximately 80 percent of these cancers are confined to the lining or the tissue just underneath the lining. About 20 percent invade the muscle of the bladder and can spread to the pelvic lymph nodes. In men, bladder cancer can spread into the prostate and seminal vesicles, and in women these cancers can invade the cervix, the uterus, and the vagina. When bladder cancer spreads beyond the confines of the pelvis, it can invade lymph nodes around the heart and spread to other organs, most commonly the lung, liver, or bones.
Cancers are categorized and described by stage and grade.
Bladder cancer usually is associated with blood in the urine (hematuria) (termed "gross hematuria" when blood is visible in the urine). Patients may report rust-colored urine or the passing of tissue, clots or blood. Approximately 10 percent of patients with gross hematuria will be found to have a bladder tumor.
Frequently, however, urine that appears perfectly normal to the naked eye will be shown by the microscope to contain abnormal numbers of red blood cells (microhematuria). This condition can be diagnosed by a simple analysis of the patient's urine in the doctor's office.
Other symptoms include burning or frequency of urination in the absence of a urinary tract infection and pelvic pain along with the symptoms mentioned above.
Bladder cancer is diagnosed by cystoscopy, a procedure in which the urologist passes a lighted telescope through the urethra into the bladder and looks directly at the inside lining of these structures. Through a cystoscope, a biopsy can be performed, and, frequently, if a tumor is found, it can be completely removed.
A rectal examination in a male and a vaginal bimanual examination in a female may reveal a mass on the outside surface of the bladder.
Once the pathologist establishes the diagnosis of bladder cancer, additional tests are required, possibly including x-rays of the kidneys and bladder, ultrasound and an intravenous pyelogram in which iodinated contrast is injected intravenously. Alternatively, a computed tomography scan, or CT scan, may be performed. An additional urine test called cytology will be performed. This is a method of detecting cancer cells under the microscope very similar to a PAP smear for women. Blood tests will include BUN and creatinine measurements, which evaluate the total kidney function.
If the cancer is invasive, spread to the lymph nodes and other organs must be evaluated. These examinations will include a chest x-ray to look at the lungs and a CT scan to look at the liver and lymph nodes. Blood tests will include liver function studies, a complete blood count, and evaluation of serum electrolytes. Blood tests that serve as markers of advanced disease might include a beta-hCG, CEA, CA125 or CA19.9. Newer tests, including those for TGF-beta, IL-6, urokinase type plasminogen activator, and other markers, are being done in our clinic.
Treatment of Superficial Bladder Cancer
Resection of the tumor through a cystoscope frequently is adequate treatment for carcinoma in situ and papillary Ta and T1 cancer low-grade tumors. Over time these tumors have a tendency to recur and, therefore, regular cystoscopy is performed in the office to examine the bladder. Urinalysis and cytology will also be performed, usually every 3 months for 1 to 2 years, and then annually. For patients who experience multiple tumors or recurrent tumors or any high-grade cancer, additional therapy is warranted in an attempt to reduce the probability of recurrence and/or progression to a more aggressive cancer.
Chemotherapy drugs, such as Mitomycin C, are instilled into the bladder weekly for six weeks. This is done in the office. The catheter is placed through the urethra into the bladder. The drug is left in place for two hours. Six weeks after completion of the therapy, another cystoscopy is performed to evaluate the status of the bladder. The most common intravesical treatment is Bacillus Calmette-Guerin (BCG). This bacteria, which is a relative of the bacteria that causes tuberculosis, is the most effective agent that a urologist has to prevent the recurrence of bladder cancer. The bacteria attaches to the lining of the bladder and stimulates the immune system to kill any incipient cancer cells. This treatment is also administered weekly for six weeks and may be given in combination with interferon-alpha, another drug that stimulates the immune system. Following the initial 6-week course, biopsies usually will be performed through a cystoscope in the operating room. Treatments will be repeated at months 3 and 6, and then every 6 months for up to 3 years in order to provide ongoing stimulation of the immune system. Approximately 15 to 20 percent of patients with this early stage of bladder cancer will develop a more aggressive, invasive type of cancer.
Treatment Options for Invasive Cancer
When the cancer invades the muscle or deeper portions of the bladder, the risk of the cancer spreading to the lymph nodes is approximately 20 percent. Complete removal of the bladder (cystectomy) is the treatment of choice, as this provides excellent control of the primary tumor and removes all of the primary lymph node drainage and any potential cancer-bearing lymph nodes. In a male this operation includes removal of the prostate and seminal vesicles. The male urethra is removed only when there is involvement of the prostate substance. In a woman the uterus and ovaries are removed in postmenopausal women, and infrequently, a small portion of the vagina must be removed. Vaginal reconstruction is performed in sexually active women.
When the bladder is removed, the urinary tract must be reconstructed to allow passage of the urine. This is called a "urinary diversion." In a male the nerves responsible for the urge for erections run alongside the prostate, and a nerve-sparing operation can be done in order to preserve erectile function. When it is necessary to remove these nerves, a nerve graft can be performed to bridge the gap between the cut ends of the nerves. The nerve graft is harvested from the sural nerve, which is on the outside of the ankle and is commonly used for nerve graft procedures in other parts of the body.
There are three general choices for bladder reconstruction. The simplest and easiest to perform is called a "conduit." In this procedure a portion of the small intestine, approximately six to eight inches long, is separated from the remaining intestine and is closed off at one end. It is brought to the skin as a "stoma" and the ureters, the tubes that drain the kidneys, are connected to the segment of intestine, and the urine drains continuously into a bag placed over the skin. Patients can enjoy an excellent quality of life with resumption of most of their preoperative activities.
In the past 10-15 years we have had significant experience with "continent urinary diversion." A reservoir made out of large or small intestine is created internally out of a segment of bowel. The ureters are connected to the reservoir, which serves as an excellent storage site, mimicking the capacity of the bladder. Approximately 90 percent of men and 75 percent of women are suitable candidates for reconstruction of the urethra as long as they have good bladder sphincter function and there is no cancer involving the opening of the bladder or the urethra itself. This so-called "orthotopic diversion" is associated with daytime control of urine exceeding 90 percent. At night, the urethra relaxes and there is a higher incidence of leakage of urine as the bladder fills. Patients need to get up once or twice at night and often set an alarm so they can remain dry. Patients older than 65 or 70 years old have a higher incidence of leakage at night, although they maintain a high probability of staying dry during the day.
For patients in whom the urethra is not suitable for use or must be removed, the internal reservoir is connected to the skin by a small piece of intestine as a stoma. The patient stays dry and empties the bladder by placing a small tube called a catheter through the stoma into the bladder to drain it. This is procedure is required four to six times a day
Alternative to Cystectomy
For patients in whom the risks of surgery are prohibitive, usually because of preexisting lung or heart disease, radiation therapy is an acceptable alternative to cystectomy. This may be administered in combination with a radiosensitizing chemotherapy drug, such as cisplatin, in order to boost the effect of the radiation therapy. For patients who are interested in bladder salvage and are medically fit, experimental programs combining multi-agent chemotherapy, radiation therapy, and extensive tumor resection via cystoscopy can be performed. These treatments are associated with a slightly lower probability of long-term cure than cystectomy and lymph node removal.
When the bladder is removed, the pathologist examines in detail the bladder and any adjacent structures, as well as the lymph nodes. For patients with node metastasis, we will usually recommend additional chemotherapy after recovery from cystectomy. In young patients with T3 or T4 tumors but no evidence of lymph node metastasis, chemotherapy may be recommended as well.
Treatment of Metastatic Bladder Disease
At the time of the initial diagnosis in approximately five percent of patients, the disease will already have spread to lymph nodes outside the pelvis or to other organs, such as lung, liver, and bones. These patients can be treated with multi-agent chemotherapy. We are testing a regimen including VC drugs plus taxotere and bringing investigational drugs into the treatment arena for these patients.
The treatment for both superficial and invasive bladder cancer is becoming more sophisticated daily as we gain knowledge of the behavior of these cancers, identifying new targets for therapy and improving surgical techniques and both chemotherapy and immunotherapy. At Baylor we have an extensive clinical trials program, led by Dr. Seth P. Lerner. In our laboratories we are investigating new approaches to treatment including gene therapy in collaboration with the Center for Cell and Gene Therapy at Baylor. In addition, we are investigating a number of different markers that can be measured in tissue, urine, and the blood to assess prognosis and provide guidance for the therapy.