Patients with Stage III bladder cancer have cancer that invades through the connective tissue and muscle and into the immediate tissue outside the bladder and/or invades the prostate gland in males or the uterus and/or vagina in females. With Stage III bladder cancer, there is no spread to lymph nodes or distant sites. Stage III bladder cancer is classified as a “deep” or “invasive” bladder cancer. 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 III 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.
There are essentially two ways to treat patients with Stage III bladder cancer: primary surgical treatment consisting of radical cystectomy with some form of urinary diversion or combined modality treatment consisting of administration of chemotherapy and/or radiation therapy, followed by radical cystectomy only for those patients who do not achieve a complete response. Patients who achieve a complete response following chemotherapy are followed closely and are treated with a radical cystectomy if cancer returns. It is important to realize that several physicians, including a urologist, a medical oncologist and a radiation oncologist, may be required to assist you in making the appropriate decision concerning the initial choice of treatment for Stage III bladder cancer.
The general health condition of the patient may also help determine which approach to treatment is most appropriate. It is important to consider whether the patient is well enough to undergo radical cystectomy and creation of an artificial bladder. It is the general health condition, rather than age, that can be the limiting factor for this type of surgery. For patients in good condition, the choice will depend on the extent of cancer and the preferences of the patient and treating physicians.
Surgery as Primary Treatment
Radical cystectomy is considered a standard treatment for Stage III bladder cancer. A radical cystectomy involves removal of the bladder, tissue around the bladder, the prostate and seminal vesicles in men and the uterus, fallopian tubes, ovaries, anterior vaginal wall and urethra in women. In addition, a radical cystectomy may or may not be accompanied by pelvic lymph node dissection.
Radical cystectomy was once considered a procedure that seriously affected a patient’s quality of life. With the creation of artificial bladders, referred to as continent reservoirs or “neobladders,” that preserve voiding function, a radical cystectomy is now a far more acceptable procedure.
To learn more about cystectomy, go to Surgery for Bladder Cancer.
Chemotherapy Prior to Cystectomy
Following a radical cystectomy, local recurrence of cancer is uncommon because the cancer was removed. Despite undergoing complete removal of the bladder, however, some patients will still develop distant recurrences because undetected cancer cells called micrometastases spread to other locations in the body before the bladder was removed. Treatment with a systemic (whole-body) therapy such as chemotherapy may reduce or eliminate these micrometastases.
Neoadjuvant chemotherapy refers to chemotherapy that is given before surgery. The rationale behind neoadjuvant therapy for bladder cancer is two-fold. First, pre-operative treatment can shrink some bladder cancers and therefore, may allow more complete surgical removal of the cancer. Second, because chemotherapy kills undetectable cancer cells in the body, it may help prevent the spread of cancer when used initially rather than waiting for patient recovery following the surgical procedure.
A study published in the New England Journal of Medicine reported that patients with muscle-invasive bladder cancer who received chemotherapy prior to cystectomy had better survival than patients treated with cystectomy alone.1
Chemotherapy and Radiation Therapy as Primary Treatment
Over the past decade, there have been many studies in the United States and Europe evaluating the combination of radiation and chemotherapy for initial treatment of patients with Stage III bladder cancer for the purpose of preserving the bladder. Bladder-preserving therapy is appealing because patients who achieve a complete response to treatment can often avoid additional treatment with a radical cystectomy unless they experience recurrence of their cancer. In addition to avoiding a cystectomy, early treatment with chemotherapy may also kill bladder cancer cells that have already spread away from the bladder.
In some clinical trials, approximately half or more of patients who were treated with bladder-preserving therapy (initial TUR of as much cancer as possible, plus chemotherapy and radiation therapy) survived cancer-free for three to four years after treatment. These results appear as good as those observed with radical cystectomy, but there have been no direct comparisons of radical cystectomy to combination chemotherapy and radiation therapy without surgery. Furthermore, only selected patients with Stage III bladder cancer will be candidates for bladder-preserving therapy. As a result, some physicians think that bladder-preserving surgery should be limited to clinical trials and not adopted as standard therapy.
Chemotherapy Alone as Primary Treatment
Chemotherapy without radiation therapy may be used for selected patients with inoperable stage III cancer, or for patients who cannot tolerate more extensive treatment.2
Radiation Therapy Alone as Primary Treatment
Currently, the use of radiation therapy alone as a primary treatment for bladder cancer has largely been replaced by the combined use of radiation therapy and chemotherapy. However, there may be some patients who cannot tolerate chemotherapy and radiation alone is still beneficial. To learn more go to Radiation Therapy for Bladder Cancer.
Questions to Ask Your Physician About the Treatment of Stage III Bladder Cancer
- What are the long-term results of radical cystectomy at the treating institution?
- What is the quality of life with the type of artificial bladder constructed at the treating institution?
- What are the long-term results of bladder-sparing treatments at the treating institution?
Strategies to Improve Treatment
The progress that has been made in the treatment of bladder cancer has resulted from improved treatment developed in clinical trials. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.
Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.
Adjuvant Treatment: It is important to realize that some patients with Stage III cancer already have small amounts of cancer that spread away from the bladder. Undetectable areas of cancer are referred to as micrometastases and cannot be detected with any of the currently available tests. It is the presence of micrometastases that usually causes the relapses that follow treatment with a cystectomy alone.
Adjuvant therapy is a treatment that follows surgical cystectomy. In contrast to neoadjuvant chemotherapy, there is currently no proven benefit from receiving adjuvant chemotherapy and/or radiation therapy after surgery. Adjuvant chemotherapy is still being evaluated in clinical trials to prevent recurrence of bladder cancer. As new drug combinations are developed, it may be very important to participate in these clinical trials.
Chemotherapy Combined with Biologic Agents: Combining chemotherapy with biologic agents is the focus of intensive investigation.
Multiple Drug Resistance Inhibitors: Bladder cancer can be drug resistant at the outset of treatment. Drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in bladder cancer.
Gene Therapy: Currently, there are no gene therapies approved for the treatment of bladder cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene and/or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer cell death and efforts to facilitate immune mediated death of cancer cells. A few gene therapy studies are being carried out in patients with refractory bladder cancer. If successful, these therapies could be applied to patients with earlier stage disease.
1 Grossman HB, Natale RB, Tangen CM et al. Neoadjuvant Chemotherapy Plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer. New England Journal of Medicine 2003.239:859-66.
2 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Bladder Cancer. V.2.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN and NATIONAL COMPREHENSIVE CANCER NETWORK are registered trademarks of National Comprehensive Cancer Network, Inc.