Patients with stage 0 (T0) or (Tis) bladder cancer have the earliest stage of bladder cancer that involves only the surface layer of the bladder. Depending upon the appearance of cancer cells under the microscope, stage 0 bladder cancer is pathologically classified as a non-invasive papillary carcinoma or carcinoma in situ (CIS).
A variety of factors ultimately influence a patient's decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient's chance of cure, or prolong a patient's survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of stage 0 bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
Both non-invasive papillary carcinoma and carcinoma in situ are classified as superficial bladder cancers. Standard treatment of superficial bladder cancer is surgical removal through a cystoscope and adjuvant therapy to decrease the risk of recurrent cancer or progression to more invasive disease. Despite standard treatment, the majority of patients with superficial bladder cancer experience recurrence of their cancer. Research is ongoing to evaluate several new approaches for the treatment of superficial or recurrent superficial bladder cancer.
Non-Invasive Papillary Carcinoma Papillary carcinoma of the bladder is a superficial cancer that grows on the surface of the bladder and can be easily removed with surgery. Standard treatment of papillary carcinoma is a transurethral resection (TUR). A TUR is an operation that is performed for both the diagnosis and management of bladder cancer. During a TUR, a urologist inserts a thin, lighted tube called a cystoscope into the bladder through the urethra to examine the lining of the bladder. The urologist can remove samples of tissue through this tube or can remove some or all of the cancer in the bladder.
Following a TUR, the standard approach for the management of patients with non-invasive papillary carcinoma is surveillance, which means frequent follow-up examinations. During surveillance, patients undergo frequent evaluations performed at regular intervals to detect recurrent or new cancers before they become invasive. Routine surveillance tests include urinary cytology (looking for new cancer cells in the urine) and direct visualization of the lining of the bladder (cystoscopy) typically performed every 3 months. Recurrences can be expected to occur in 50-75% of patients but are usually of the same grade and stage as the original cancer and can be successfully treated by repeat TUR.
Carcinoma In Situ (CIS) Carcinoma in situ is a superficial bladder cancer that is confined to the surface layer of the bladder. The cellular growth pattern of CIS differs from that of papillary carcinoma. Furthermore, CIS is more likely than papillary carcinoma to lead to invasive bladder cancer.
All patients with CIS are initially treated with transurethral resection (TUR), biopsy with electrical (cautery) or laser thermal destruction of all visualized cancer. Radical cystectomy (complete removal of the bladder) is used for treatment of extensive multiple superficial cancers or CIS unresponsive to intravesical therapies.
TUR alone is effective in preventing recurrences in approximately 50% of patients with superficial bladder cancer. Failure of treatment is usually due to the appearance of new superficial cancers, which can be retreated with TUR and cautery or laser therapies. Within 15 or 20 years, more than half of surviving patients will have experienced progressive cancer or have developed new cancers, including cancers of the upper urinary tract (ureters and pelvis of the kidney). Approximately 20-30% of these cancers will require treatment with cystectomy.
Since this is a cancer of older individuals, many patients will die of other causes before progression of bladder cancer. However, approximately 25% of patients treated for superficial bladder cancer will ultimately die of bladder cancer. Since the risk of developing invasive bladder cancer never goes away, it is important to have frequent follow-up examinations (cystoscopy) no matter what form of therapy is selected. It is extremely important to detect early progression because there are effective treatments for small invasive bladder cancers.
Adjuvant Treatment
Since recurrences of bladder cancer can occur frequently, it is important to develop strategies to prevent these recurrences. Adjuvant therapy is additional treatment that increases the effectiveness of a primary therapy. The goal of adjuvant therapy is to improve the chance of cure, prevent cancer from recurring or progressing to a worse stage and or to improve the duration of overall survival. Adjuvant therapy for papillary carcinoma and carcinoma in situ typically consists of chemotherapy and/or biologic therapy following surgery. Delivery methods for adjuvant therapy differ depending on the needs of patients. While some adjuvant treatments are delivered systemically, others are delivered directly into the bladder. One form of adjuvant treatment for bladder cancer utilizes instillation of anti-cancer substances through the urethra into the bladder. Patients with carcinoma in situ are at particular risk not only for superficial cancer recurrences, but also for progression to more aggressive invasive bladder cancers. All patients with this stage of disease should consider adjuvant treatment.
Bladder Instillation of Bacille Calmette-Guérin (BCG): Bacille Calmette-Guérin (BCG) is one of the most common adjuvant therapies for treatment of superficial bladder cancer. In fact, BCG instilled directly into the bladder is considered to be a standard adjuvant treatment for bladder cancer. BCG is an immunotherapy that is a weakened form of the bacterium related to bacteria causing tuberculosis. BCG is instilled directly into the bladder through the urethra and exerts its anti-cancer effect by stimulating the body's immune system to kill cancer cells. The primary side effects of BCG are pain in the bladder, blood in the urine and rarely, autoimmune disorders. Because BCG is a live bacteria, it may occasionally grow and cause an infection that requires antibiotic treatment.
The anti-cancer response rate of superficial bladder cancers to the periodic instillation of BCG into the bladder is approximately 70%. Treatment with BCG delays progression to muscle-invasive and/or metastatic bladder cancer, improves the rate of bladder preservation and decreases the risk of death from bladder cancer. With BCG immunotherapy, 65% of patients who have a complete response will remain cancer-free for 5 years. With improved maintenance, BCG schedules (booster doses given at 3 month intervals up to 2-3 years), complete responses have been increased to over 80% with 80% of the complete responders remaining disease-free. In some situations, BCG is also given by injection into the skin similar to the method for prevention of tuberculosis. Currently, the exact contribution of systemic vaccination to overall outcome is not clear and most urologists no longer use this technique.
At the Memorial Sloan-Kettering Cancer Center, a clinical trial was performed that evaluated BCG that was administered to prevent recurrence of superficial bladder cancer. In this clinical trial, treatment with surgery alone (TUR) was compared to surgery (TUR) followed by BCG injected into the bladder weekly for 6 weeks. Eighty-six patients were randomly assigned to one of the two treatment regimens and the results were then directly compared. At 10 years from initiation of treatment, 62% of patients receiving BCG survived without progression to more invasive bladder cancer, compared to only 53% for patients treated with surgery alone. Eighteen patients treated with surgery alone were also given BCG an average of 29 months after initial treatment and 15 did not experience cancer progression. Management of superficial bladder cancer with surgery plus BCG resulted in a 10-year cancer-specific survival of 75%, compared to 55% with surgery alone.Results from this clinical study demonstrated that BCG is a standard treatment for patients with superficial bladder cancer because it showed that BCG administered into the bladder after surgery delayed cancer progression and death from invasive bladder cancer. However, even with optimal BCG therapy, almost half of all patients with superficial bladder cancer will ultimately have progression to invasive bladder cancer. This indicates the importance of frequent follow-up examinations (cystoscopy) to detect early progression to invasive cancer or new superficial cancers. Early invasive bladder cancer can be treated effectively.
Bladder Instillation of Chemotherapy: Instillation of chemotherapy into the bladder is considered a second-line therapy, while the preferred initial adjuvant therapy is BCG. However, instillation of chemotherapy is very effective in patients who are at a low risk of recurrence. Instillation of chemotherapy drugs (Mutamycin®, Thioplex®, or doxorubicin) into the bladder can reduce the incidence of superficial cancer recurrences, but no single drug has been confirmed to reduce progression of superficial cancer to invasive bladder cancer. This means that multiple small new cancers can be prevented, but progression to a more invasive bladder cancer may occur despite treatment.
The optimal time to administer chemotherapy is immediately after TUR, as the drugs might prevent reseeding of cancer cells that were disrupted with surgery. Mutamycin® is probably the preferred drug because it produces few side effects and is not well absorbed into the system, which allows more of the drug to remain in the bladder to treat the cancer. Thioplex® is rapidly absorbed and produces low blood counts. Doxorubicin produces the most local side effects.
Mutamycin® has been evaluated in patients with superficial bladder cancer. During a clinical study in Sweden, 261 patients were treated with either bladder instillations of BCG or Mutamycin®. After an average follow-up of 64 months, 42% of patients were without evidence of superficial cancer recurrence. A significant improvement was noted in the cancer-free survival of patients with superficial bladder cancer following treatment with BCG, which was most pronounced in patients with carcinoma in situ. There was no difference in progression to a more invasive bladder cancer or survival between patients receiving BCG or Mutamycin®. Thirty-nine percent of patients who failed Mutamycin® responded to BCG and 19% of patients who failed BCG responded to Mutamycin®. These physicians concluded that BCG was superior to Mutamycin® for prevention of superficial recurrences, but there was no difference in progression to more invasive cancers or survival between the two treatments.
Other clinical trials have shown the superiority of bladder instillation with BCG to doxorubicin in preventing recurrences of superficial bladder cancers.
Strategies to Improve Treatment
The progress that has been made in the treatment of bladder cancer has resulted from improved surgical techniques, development of adjuvant treatments and doctor and patient participation in clinical studies. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration to improve the treatment of bladder cancer. |
