Bladder cancer treatment; invasive cancer

Patient information: Bladder cancer treatment; invasive cancer

Author
Andrew J Stephenson, MD
Section Editor
Seth P Lerner, MD
Deputy Editor
Don S Dizon, MD, FACP

Disclosures

BLADDER CANCER OVERVIEW — The optimal treatment for urothelial (transitional cell) bladder cancer depends upon the cancer’s stage and grade, and also on the health of the patient.

Approximately 70 percent of all new cases of bladder cancer are classified as non-muscle-invasive or superficial. The initial treatment for superficial bladder cancer is surgical removal of the tumor through a cystoscope (called transurethral resection of bladder tumor, or TURBT). This is often followed by adjuvant (additional) therapy, which reduces the chances of the cancer recurring. (See “Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer”.)
The remaining 30 percent are invasive bladder cancers, and generally require surgical removal of the bladder (cystectomy) and some surrounding organs.
This article will review the treatment of invasive urothelial bladder cancer. The diagnosis and staging of bladder cancer and the treatment of superficial bladder cancer are discussed separately. (See “Patient information: Bladder cancer diagnosis and staging” and “Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer”.)

WHAT IS INVASIVE BLADDER CANCER? — Bladder tumors are staged using the TNM system, which indicates how deeply the tumor has penetrated (T stage), whether it has reached the nodes (N) and whether it has spread or metastasized to other parts of the body (M); these stages are then grouped as 0 through IV, and this helps the doctor to decide what type of treatment to use.

Invasive bladder cancer is stage T1 or greater, meaning that the tumor has invaded the lining of the bladder. If the tumor has invaded the muscle layer of the bladder, it is stage T2. Stage T3 cancer has grown through the bladder muscle into the fat layer surrounding the bladder, while stage T4 cancer has spread to nearby organs.

BLADDER CANCER TREATMENT OPTIONS — The standard treatment for muscle-invasive bladder cancer includes surgery to remove the bladder and nearby organs (called radical cystectomy). Lower stage invasive bladder cancer (stage T1 tumors) may be treated with radical cystectomy or intravesical BCG. (See “Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer”, section on ‘Intravesical BCG’.)

Radical cystectomy requires the creation of a new way to get rid of urine. (See ‘Where will the urine go?’ below.) In some cases, it is possible to avoid cystectomy by having a bladder preserving treatment. However, this treatment is not an option for most people with muscle-invasive bladder cancer due to the high risk that the cancer will come back (called a recurrence).

For patients with muscle-invasive bladder cancer who are able to tolerate more aggressive treatment, chemotherapy is often given before surgery (called neoadjuvant chemotherapy).

Which treatment is best? — The best treatment for invasive bladder cancer depends upon the person’s age, underlying medical problems, stage of the bladder cancer, and personal preference. When possible, surgical removal of the bladder is preferred because it has a lower chance of cancer recurrence and better chance of survival compared to other treatments. However, preserving the bladder may be an option in selected cases.

Cystectomy is preferred for patients who have:

Invasive bladder cancer and are not candidates for bladder preservation
Low-stage or superficial cancers that have recurred after intravesical BCG
High-grade T1 cancers (intravesical BCG is a reasonable alternative)
Bladder preservation may be an option for patients who:

Are elderly or who have serious underlying medical problems and would not be able to tolerate a major surgery
Strongly prefer to keep their bladder AND have a single, well-defined, muscle-invasive tumor inside the bladder, without any evidence of carcinoma in situ (which often recurs) or hydronephrosis (enlargement of the kidneys)
CYSTECTOMY (SURGICAL REMOVAL OF THE BLADDER) — Patients with muscle-invasive bladder cancer who need to have cystectomy are sometimes advised to have chemotherapy before surgery, if the patient is healthy enough to tolerate this more aggressive treatment.

Neoadjuvant chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (such as cancer cells) to divide or reproduce themselves. Because most of an adult’s normal cells are not rapidly growing, they are not affected by chemotherapy. Exceptions to this include cells of the bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. These tissues are affected most by chemotherapy, causing the typical side effects (low blood counts, hair loss, etc).

Neoadjuvant chemotherapy is the term used to describe chemotherapy given before surgery. When possible, people with muscle-invasive bladder cancer are usually advised to have neoadjuvant chemotherapy before cystectomy.

The reason for this recommendation is that chemotherapy helps to eliminate undetectable cancer cells that are often found in other areas of the body in people with invasive cancer. By eliminating these cancer cells, chemotherapy helps to improve survival. Clinical trials have shown that neoadjuvant chemotherapy reduces the risk of death and improves five-year survival in people with invasive bladder cancer [1].

The chemotherapy regimen usually includes a combination of four drugs: methotrexate, vinblastine, doxorubicin, and cisplatin (abbreviated MVAC). The regimen is usually given into a vein during the daytime. Occasionally, the patient may require an overnight stay in the hospital for the chemotherapy treatments. During the first two days, all of the medications are given together. Methotrexate and vincristine are then given again 15 and 22 days later. This is referred to as one cycle. A new cycle is started one week later.

A cycle of chemotherapy refers to the time it takes to give the treatment and then allow the body to recover from the effects. During this time, patients are closely monitored for signs of drug toxicity and side effects. Three cycles of MVAC are usually recommended before cystectomy.

Chemotherapy side effects — The most common side effects of MVAC include fatigue, increased risk of infection, bruising or bleeding easily, complete hair loss, mouth soreness, nausea or vomiting (usually can be prevented or treated), decreased hearing or ringing in the ears, numbness or tingling in the hands or feet, and pink-red colored urine. These side effects are usually temporary and resolve after treatment is completed.

Cystectomy procedure — Radical cystectomy includes removal of the bladder, nearby organs, and associated lymph nodes.

In men, radical cystectomy generally includes removal of the bladder, as well as the prostate, and seminal vesicles (figure 1). Because of the extent of the surgery, nerve damage can occur, leading to erectile dysfunction (inability to have or maintain an erection). (See ‘Nerve-sparing procedures’ below.)
In females, radical cystectomy includes removal of the bladder, as well as the uterus, cervix, and upper vagina (figure 2).
Where will the urine go? — After the bladder is removed, the surgeon must create a new place for urine to be collected. This is called a urinary diversion. All options involve using a segment of bowel, which is removed from the small or large intestine. After removing a segment of bowel, the intestines are reattached so that they function normally. The section of bowel that is removed is cleaned and prepared.

There are several possible options at this point:

Urine can be diverted through a segment of bowel to the skin’s surface, where an opening (called a stoma) is created. A bag is attached to the stoma to collect the urine. This is called a non-continent cutaneous diversion or ileoconduit (figure 3).
A reservoir (like a pouch) may be created under the skin of the abdomen using tissue from the stomach or intestines. Urine collects in the pouch, and the patient uses a catheter (a thin tube) to empty the pouch periodically. It is not necessary to wear a bag. This is called a continent cutaneous diversion, commonly called an Indiana pouch (figure 4).
A new bladder may be created from a segment of bowel. The new bladder is connected to the urethra, allowing the person to urinate normally. This is called an orthotopic neobladder, commonly called a Studer neobladder or pouch (figure 5).
The “best” type of urinary diversion depends upon the patient and surgeon’s preference, as well as the extent of the cancer. In addition, the continent reservoir and neobladder require the person to learn how to self-catheterize; patients who would have difficulty handling or placing the catheter may not be good candidates for these procedures.

Complications of urinary diversion — Some of the potential complications of urinary diversion include leakage of urine, urinary tract infection, skin irritation (with stoma or pouch), and narrowing or closure of the tissue where urine exits. The risk of each of these depends upon which procedure is performed. To understand the risks and benefits of each type of diversion, talk with your surgeon.

Lymph node removal — Lymph fluid from the bladder normally drains into lymph nodes (glands) located in the pelvis. If the cancer has spread to lymph nodes, there is a much higher risk that the cancer has also spread elsewhere. This significantly increases the risk of the cancer recurring at a later time.

An important part of radical cystectomy is removal of all lymph nodes that could contain tumor cells. This includes lymph nodes in the pelvic region, and in some cases, also includes more distant lymph node groups. The patient should talk to his or her surgeon about which nodes will be removed as there is increasing evidence that removing more lymph node groups (rather than the standard groups) may improve survival [2].

Nerve-sparing procedures

Men — In men, surgical removal of the prostate and seminal vesicles (figure 1) can damage the nerves responsible for achieving and maintaining an erection. Men who want to preserve their ability to have an erection are sometimes able to have a nerve-sparing surgery, which reduces the risk of nerve damage. This procedure is only available to men who have no evidence of cancer in the bladder neck or prostatic urethra, no carcinoma in situ, and no evidence of prostate cancer.

About 30 to 50 percent of men who have nerve-sparing cystectomy are able to have an erection sufficient for sexual intercourse one to two years after surgery [3]. Most of these men will require an oral medication, such as sildenafil (Viagra®), to have an erection. (See “Patient information: Sexual problems in men”.)

One potential risk of nerve-sparing surgery is that an insufficient amount of cancerous tissue will be removed from around the nerves. However, several studies have shown that bladder cancer recurrence rates are similar in men who have nerve-sparing and traditional radical cystectomy when patients are carefully screened before surgery [4].

Women — In women, nerve-sparing surgery involves careful removal of tissue on each side of the vagina, where nerves responsible for sexual function are found. Nerve-sparing surgery may help to prevent vaginal dryness, pain with intercourse, and loss of the ability to have orgasm.

Surgical complications — Up to 60 percent of patients who have radical cystectomy and urinary diversion develop some type of complication. The most common serious complications include infection, wound opening, bleeding, and blood clots in the lungs (pulmonary embolus). The surgeon’s and hospital’s experience in performing cystectomy, as well as the patient’s age and any underlying medical problems, affect the risk of developing complications.

Chemotherapy after cystectomy — In some situations, chemotherapy is not given before cystectomy. However, chemotherapy may be recommended after surgery (called adjuvant chemotherapy) if more extensive disease is found when the bladder is removed. For example, chemotherapy may be recommended after cystectomy for those healthy enough to tolerate it if:

The tumor extends into the perivesical fat surrounding the bladder (tumor stage T3 or higher)
Lymph nodes in the region are positive
The best chemotherapy regimen is not clear; patients are encouraged to enroll in a clinical trial if possible. (See ‘Clinical trials’ below.)

Outcomes — The outcomes following radical cystectomy for bladder cancer depend upon the stage and extent the cancer and lymph node involvement [5]. Talk to your doctor or nurse if you have questions about your cancer.

BLADDER PRESERVATION — In selected people with invasive bladder cancer, it may be possible to avoid removing the entire bladder. The possible risk of this approach is that the bladder cancer may be more likely to recur.

Bladder preservation options include:

Radical transurethral resection of bladder tumor (TURBT)
Partial removal of the bladder
Chemotherapy and radiation (chemoradiotherapy), which are performed after radical TUR
Risk of recurrence with bladder preservation — Between 30 to 60 percent of patients who have bladder preservation will develop recurrent bladder tumors, approximately half of which are invasive. If this occurs, the recommended treatment is immediate cystectomy.

Overall survival in patients who develop a recurrence and then undergo cystectomy is 40 to 50 percent; this is probably 10 to 20 percent lower compared to immediate treatment with radical cystectomy. This is important to consider when deciding upon a treatment plan.

Radical transurethral resection of bladder tumor (TURBT) — Radical TURBT is a procedure in which a physician uses a cystoscope to view the lining of the bladder and remove any abnormal-appearing areas. This is similar to the procedure used to treat superficial bladder cancer.

However, radical TURBT is a more aggressive than standard TURBT; the physician will remove any abnormal appearing areas as well as the underlying bladder muscle down to the layer of fat surrounding the bladder (called perivesical fat).

Several weeks after the radical TURBT, the physician will use the cystoscope to look inside the bladder again. If there is no evidence of cancer, the patient will be followed closely.

If there is evidence of cancer, surgical removal of the bladder is usually recommended, sometimes with neoadjuvant chemotherapy given before surgery. (See ‘Cystectomy procedure’ above.)

Partial bladder removal (cystectomy) — Partial cystectomy is a surgical procedure in which the bladder tumor and some surrounding bladder tissue are removed, allowing the person to keep the healthy tissue. The surgery is done through a midline (up and down) incision in the lower abdomen. Removal of involved lymph nodes is also performed. (See ‘Lymph node removal’ above.)

Partial cystectomy is not an option for most people, but may be available for people with certain characteristics, including a single small tumor at the top of the bladder. People who have recurrent bladder cancer or involvement of other areas (urethra, lower bladder) are not good candidates for partial cystectomy.

The advantage of partial cystectomy is that it allows the person to urinate “normally” after surgery and does not usually interfere with sexual function. The disadvantage is that there is a higher risk of bladder cancer recurrence. Approximately 70 percent of patients survive long-term after partial cystectomy [6].

Chemoradiotherapy — Chemoradiotherapy is a treatment that involves having radiation therapy to the bladder and pelvis, along with chemotherapy. Removal of all visible evidence of cancer with TURBT is recommended before proceeding to chemoradiation. Chemoradiation is less likely to be successful in patients who have residual cancer in the bladder at the start of therapy.

Radiation therapy involves the use of focused, high energy x-rays to destroy cancer cells. The x-rays are delivered from a machine that is outside of the patient. The damaging effect of radiation is cumulative, and a certain dose is required to stop the growth of cancer cells. In order to accomplish this, small radiation doses are administered for a few seconds each day (similar to having an x-ray), five days per week, for several weeks. Treatment is not painful.

A chemotherapy drug, such as cisplatin, is usually given once every three weeks into a vein during radiation therapy. Cisplatin makes the tumor cells more sensitive to the radiation treatment, improving the chance of eliminating the cancer.

CLINICAL TRIALS — Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

www.cancer.gov/clinicaltrials/learning/

www.cancer.gov/clinicaltrials/

file://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer
Patient information: Bladder cancer diagnosis and staging
Patient information: Sexual problems in men

Professional Level Information:

Adjuvant chemotherapy for urothelial (transitional cell) carcinoma of the bladder
Chemoprevention of bladder cancer
Clinical presentation, diagnosis, and staging of bladder cancer
Epidemiology and etiology of urothelial (transitional cell) carcinoma of the bladder
Etiology and evaluation of hematuria in adults
Experimental systemic therapy of metastatic bladder cancer
Laparoscopic radical cystectomy
Multimodality approaches for bladder preservation in invasive bladder cancer
Neoadjuvant chemotherapy for urothelial (transitional cell) bladder cancer
Nonurothelial bladder cancer
Pathology of bladder neoplasms
Radical cystectomy and bladder-sparing treatments for urothelial (transitional cell) bladder cancer
Screening for bladder cancer
Treatment of non-muscle-invasive bladder cancer
Urinary diversion and reconstruction following cystectomy

The following organizations also provide reliable health information.

National Cancer Institute
(www.cancer.gov/cancertopics/types/bladder)

The National Library of Medicine
(www.nlm.nih.gov/medlineplus/bladdercancer.html)

American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)

Raghavan, D, Tuthill, K. Bladder Cancer — A Cleveland Clinic Guide for Patients, Cleveland Clinic Press/Kaplan Press, Cleveland 2008.
Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

About.com Cancer Forum
(file://cancer.about.com/forum)

REFERENCES
Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003; 361:1927.
Leissner J, Ghoneim MA, Abol-Enein H, et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol 2004; 171:139.
Kessler TM, Burkhard FC, Perimenis P, et al. Attempted nerve sparing surgery and age have a significant effect on urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution. J Urol 2004; 172:1323.
Schoenberg MP, Walsh PC, Breazeale DR, et al. Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup. J Urol 1996; 155:490.
Shariat SF, Karakiewicz PI, Palapattu GS, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 2006; 176:2414.
Holzbeierlein JM, Lopez-Corona E, Bochner BH, et al. Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection. J Urol 2004; 172:878.
Raghavan, D, Tuthill, K. Bladder Cancer (Cleveland Clinic Guide), Cleveland Clinic Press, Cleveland 2008.