Patients with stage II (T2) bladder cancer have cancer that invades through the connective tissue into the muscle wall, but has not spread outside the bladder wall or to local lymph nodes. Patients with cancer invading the inner half of the muscle of the bladder wall have a better outcome than patients with invasion into the deep muscle (outer half of the muscle of the bladder wall). Stage II 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 II 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 II (T2) 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 and/or radiation 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 II bladder cancer.

The general health condition of the patient may also help determine which of these two therapies 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 a standard treatment for stage II 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. Following a radical cystectomy, local recurrence of cancer is uncommon because the cancer along with the entire bladder was removed. Despite undergoing complete removal of the bladder, some patients will still develop distant recurrences because undetected cancer cells called micrometastases may have spread to other locations in the body before the bladder was removed.

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.

In some cases, stage II bladder cancer may be controlled by transurethral resection (TUR) if the cancer is small enough and does not extend far into the bladder wall. 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.

In addition, a segmental cystectomy (partial removal of the bladder) is also appropriate therapy in some patients with small cancers. Approximately 50-80% of patients with stage II bladder cancer are cured after undergoing a radical cystectomy.

Combined Modality Treatment

Chemotherapy, surgery and/or radiation therapy are increasingly used in combination to achieve the best local control of bladder cancer and improve overall survival. By administering chemotherapy prior to surgery (neoadjuvant), many physicians believe that there is an increased likelihood of preserving bladder function and improving outcomes compared to treatment with surgical cystectomy alone.

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, since 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.

Researchers from Cedars-Sinai Comprehensive Cancer Center recently presented the results of a trial comparing neoadjuvant chemotherapy followed by cystectomy to cystectomy alone in 306 patients with locally advanced bladder cancer. Neoadjuvant therapy consisted of methotrexate, Velban®, doxorubicin, and Platinol® (MVAC). Five years following treatment, approximately 57% of patients who received neoadjuvant therapy survived, compared with only 42% who were treated only with a cystectomy. The estimated average survival was doubled for patients who received neoadjuvant therapy - 6.2 years, compared with 3.8 years for patients who received only a cystectomy. In this trial, there were no chemotherapy-associated deaths and MVAC did not affect the risk of surgery or surgical complications.

Although some previous clinical trials have not demonstrated a benefit of neoadjuvant therapy in locally advanced bladder cancer, results from this particular trial indicate that neoadjuvant therapy consisting of MVAC improves survival for patients with bladder cancer compared with cystectomy alone. Future clinical trials will evaluate different neoadjuvant combinations with newer chemotherapy agents in order to improve outcomes.

Chemotherapy and Radiation Therapy for Primary Treatment

Over the past decade, there have been many clinical trials in the U.S. and Europe evaluating the combination of radiation and chemotherapy for initial treatment of patients with stage II 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 3-4 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. While bladder-preserving therapy has been widely adopted for the treatment of stage II bladder cancer, some physicians still think it should be limited to clinical trials and not adopted as standard therapy.

Chemotherapy Alone for Primary Treatment

Chemotherapy without radiation therapy as primary treatment of stage II bladder cancer has only been evaluated in one study. In that study, over 100 patients with stage II or III bladder cancer were treated with Platinol®-based combination chemotherapy and followed for an average of 10 years. The complete response rate was 54%. Forty-three patients had bladder-sparing surgery and 74% survived. Fifty-eight percent of these had a functioning bladder. Sixty-five percent of patients who had radical cystectomy after achieving a complete response survived. It is not known if these results are equivalent to radiation plus chemotherapy or initial radical cystectomy. However, the intensity of chemotherapy can be increased when not given together with radiation therapy and there is the possibility that this approach may be more effective for the prevention of metastatic cancer.

Radiation Therapy Alone as Primary Treatment

Currently, the use of radiation therapy alone has been replaced by the use of radiation therapy and chemotherapy. However, there may be some patients who cannot tolerate chemotherapy and radiation alone could be beneficial.

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.