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BLADDER CANCER OVERVIEW — Cancer of the urinary bladder is one of the most common cancers. The most common type of bladder cancer in the United States and Western Europe is urothelial carcinoma, also known as transitional cell carcinoma. The optimal treatment for urothelial bladder cancer depends on the cancer's stage (which describes how extensive the tumor is) and grade (which describes how aggressive it appears under the microscope), as well as on the person's health.
●Approximately 70 percent of all new cases of bladder cancer are classified as non-muscle invasive (previously called "superficial"). The initial treatment for non-muscle-invasive bladder cancer is a procedure called "transurethral resection of bladder tumor," or TURBT. This is sometimes followed by additional therapy, which reduces the chances of the cancer recurring. (See "Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)".)
●The remaining 30 percent are muscle-invasive bladder cancers, and they generally require surgical removal of the entire bladder. This is often combined with preoperative or postoperative chemotherapy. (See 'Cystectomy (surgical removal of the bladder)' below and 'Chemotherapy' below.)
In some cases, the cancer can be successfully treated without removing the entire bladder. (See 'Bladder preservation' below.)
This article will discuss the treatment of invasive urothelial bladder cancer. The diagnosis and staging of bladder cancer and the treatment of non-muscle invasive bladder cancer are discussed separately. (See "Patient education: Bladder cancer diagnosis and staging (Beyond the Basics)" and "Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)".)
More detailed information about bladder cancer, written for health care providers, is available by subscription. (See 'Professional level information' below.)
CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.
In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.
WHAT IS INVASIVE BLADDER CANCER? — Bladder tumors are staged using the TNM system, which stands for "tumor," "node," and "metastasis." The stage indicates how deeply the tumor has penetrated the bladder wall (T stage), whether it has reached the lymph nodes that drain the bladder (N stage), and whether it has metastasized or spread to other parts of the body (M stage). All of this information is then used to categorize the cancer into a "stage group" between 0 (least advanced) and IV (most advanced); this helps the doctor to decide on a treatment approach.
Invasive bladder cancer is stage "T1" or greater. T1 means that the tumor has invaded the superficial (surface) lining of the bladder but not the muscle layer. The treatment of T1 cancer and other non-muscle invasive bladder cancers is discussed elsewhere. (See "Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)".)
If the tumor has invaded the muscle layer of the bladder but not deeper, 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 grown directly into nearby organs. Stages T2, T3, and T4 are considered muscle-invasive bladder cancer, and treatment options for these tumors are discussed below.
BLADDER CANCER TREATMENT OPTIONS — One standard treatment for muscle-invasive bladder cancer is surgery to remove the bladder (called radical cystectomy) (see 'Cystectomy procedure' below). Radical cystectomy requires the creation of a new way to get rid of urine (see 'Where will the urine go?' below). Treatment options for non-muscle-invasive cancer are discussed separately. (See "Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)".)
In some cases, it is possible to avoid cystectomy by having a "bladder-sparing" treatment. This treatment is an option for some people with muscle-invasive bladder cancer who meet specific criteria. (See 'Bladder preservation' below.)
For people with muscle-invasive bladder cancer who are able to tolerate more aggressive treatment, chemotherapy is often given before or after surgery. (See 'Chemotherapy' below.)
Which treatment is best? — The best treatment for invasive bladder cancer depends on the stage of your cancer as well as your age, health, other medical conditions, and personal preference. In general, surgical removal of the bladder is preferred because it is associated with a lower chance of cancer recurrence and a higher chance of survival compared with other treatments. However, preserving the bladder may be an option in selected cases. (See 'Cystectomy (surgical removal of the bladder)' below and 'Bladder preservation' below.)
CYSTECTOMY (SURGICAL REMOVAL OF THE BLADDER) — Surgery to remove the bladder is the preferred approach for people who have muscle invasive bladder cancer and are not candidates for bladder preservation (see 'Bladder preservation' below). Your outcome following cystectomy will depend on the stage and extent of your cancer; your doctor or nurse can talk to you about what to expect based upon your particular situation.
In people who can tolerate it, chemotherapy prior to surgery results in better survival outcomes. If chemotherapy is not given before surgery, it may be given after surgery depending on the extent of the cancer. (See 'Chemotherapy' below.)
Cystectomy procedure — Cystectomy includes removal of the bladder, the nearby organs, and the associated lymph nodes. This procedure is also called "radical" cystectomy.
●In males, 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). However, nerve-sparing techniques have been developed which can preserve the potential of recovering sexual function in certain situations. (See 'Nerve-sparing procedures' below.)
●In females, radical cystectomy usually involves removal of the bladder as well as the ovaries, fallopian tubes, uterus, part of the cervix, and front wall of the vagina (figure 2). Some of these organs, such as the ovaries, may be preserved in certain situations.
Lymph node removal — Lymph fluid from the bladder normally drains into lymph nodes (glands) located in the pelvis. If your cancer has spread to these lymph nodes, there is a much higher risk that your 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 in the pelvic region that could contain tumor cells.
Where will the urine go? — After your bladder is removed, the surgeon must create a new place for urine to be collected inside the body. This is called a "urinary diversion." All options involve using a piece of your bowel (intestine); this can be taken from the small or large intestine. After the segment is surgically removed, the remaining bowel is reconnected so that it functions normally.
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 "urostomy" (figure 3).
●A reservoir (or pouch) may be created inside the abdomen using the bowel. Urine collects in the pouch, and you use a catheter (a thin tube) to empty the pouch periodically, a process known as "self-catheterization." It is not necessary to wear an external bag. This is called a continent cutaneous diversion, and the most common type is 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 (the tube through which urine exits the body), allowing you to urinate normally. This is called an orthotopic neobladder (commonly called a "neobladder"), and the Studer neobladder is the most common type (figure 5).
The "best" type of urinary diversion depends on your and your surgeon's preference as well as the extent of your cancer and previous treatments. The pouch and neobladder require learning how to self-catheterize; people who would have difficulty handling or placing the catheter may not be good candidates for these procedures.
Potential complications of urinary diversion include leakage of urine, urinary tract infection, skin irritation (with the stoma or pouch), and narrowing or closure of the opening where urine leaves the body (stoma). The risk of each of these depends on which type of urinary diversion is performed. Your surgeon can talk to you in more detail about the risks and benefits of each type of diversion.
Nerve-sparing procedures
Males — In males, surgical removal of the bladder, prostate, and seminal vesicles (figure 1) can damage the nerves responsible for achieving and maintaining an erection. People 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 an option if cancer is limited to within certain parts of the bladder and there is no evidence of high-risk prostate cancer. It may be possible to spare nerves on one side of the bladder/prostate but not the other if the cancer is located on only one side.
While some people who have a nerve-sparing cystectomy do retain their ability to get and maintain an erection, outcomes can vary depending on age and erectile function prior to surgery. Many people will require an oral medication, such as sildenafil (brand name: Viagra) or tadalafil (brand name: Cialis), to have an erection. (See "Patient education: Sexual problems in men (Beyond the Basics)".)
Females — In females, nerve-sparing surgery involves careful preservation of as much tissue on each side of the vagina as possible, 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. The same criteria for nerve sparing apply for females as for males.
Surgical complications — Complications can occur after radical cystectomy and urinary diversion. The most common serious complications include infection (especially wound infection or urinary tract infection), wound opening, bleeding, and blood clots in the legs (deep venous thrombosis) and lungs (pulmonary embolism). The surgeon and hospital's experience in performing cystectomy, as well as your age and any underlying medical problems, affect your risk of developing complications.
Following surgery, it is very important to follow all your doctors' instructions about rest and recovery after surgery. You will also get information about when and what to eat and drink, as well as how to manage your pain with medication. All of this can help to minimize complications and speed recovery.
Follow-up after cystectomy — Close follow-up after cystectomy is important for anyone with bladder cancer. Follow-up visits allow your doctor to check for signs that the cancer has returned and to monitor the health of your kidneys.
During a follow-up visit, you may have an exam, lab tests, imaging studies such as a computed tomography (CT) scan, and in select cases, cystoscopy to monitor any remaining parts of the urethra (the tube through which urine exits the body). (See "Patient education: Bladder cancer diagnosis and staging (Beyond the Basics)", section on 'Bladder cancer diagnosis'.)
Your doctor will advise you on how often you should have follow-up visits, which generally occur every three to twelve months for up to five years, then as needed based on your overall health and symptoms.
CHEMOTHERAPY — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Treating muscle-invasive cancer with chemotherapy prior to cystectomy is associated with better survival outcomes; thus, the combination of preoperative ("neoadjuvant") chemotherapy and surgery is widely recognized as the standard of care for patients with muscle-invasive bladder cancer. However, preoperative chemotherapy is reserved for people who are healthy enough to tolerate this more aggressive treatment. It is especially important that people considering chemotherapy have good kidney function, as the drugs used in this situation can cause further kidney damage.
If chemotherapy is not given before surgery, it may be given after surgery instead ("adjuvant" therapy) if the removed cancer was extensive. Some people have difficulty with adjuvant chemotherapy if they have a complication from surgery or are slow to recover. On the other hand, chemotherapy before surgery rarely has a negative effect on subsequent surgery. This is one reason why neoadjuvant chemotherapy is preferred.
Neoadjuvant chemotherapy — "Neoadjuvant" in this case means chemotherapy that is given prior to surgery. When possible, people with muscle-invasive bladder cancer should consider neoadjuvant chemotherapy before cystectomy.
Chemotherapy works by interfering with the ability of rapidly growing cells (including 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 blood cells are produced), the hair, and the lining of the gastrointestinal tract (gut). These tissues are affected most by chemotherapy, causing the typical side effects (low blood counts, hair loss, nausea, etc).
The benefit of neoadjuvant chemotherapy is that it helps to eliminate undetectable cancer cells that may be present in other areas of the body in people with invasive cancer. By eliminating these cancer cells, chemotherapy helps to improve survival. Getting chemotherapy prior to surgery also eliminates the possibility that surgical complications will prevent you from being able to get adjuvant chemotherapy later.
Chemotherapy after cystectomy — In some situations, chemotherapy is not given before cystectomy. However, for these people, 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 in one or both of the following situations:
●The tumor extends into the layer of fat surrounding the bladder (stage T3 or higher).
●Cancerous cells are identified in the lymph nodes that were removed during the cystectomy.
You may also consider enrolling in a clinical trial if possible. (See 'Clinical trials' below.)
Chemotherapy side effects — The most common side effects of chemotherapy include fatigue, increased risk of infection, bruising or bleeding easily, complete hair loss, mouth soreness, nausea or vomiting (which usually can be prevented or treated), decreased hearing or ringing in the ears, and numbness or tingling in the hands or feet. Most of these side effects are temporary, treatable, and resolve after chemotherapy is completed.
IMMUNOTHERAPY — Immunotherapy refers to the use of medicines that work with your immune system to attack bladder cancer cells.
Immunotherapy after cystectomy — In some situations, immunotherapy may be recommended after surgery; this is called "adjuvant" immunotherapy. Immunotherapy is an option for:
●People who have received neoadjuvant chemotherapy and cystectomy, but still have cancer invading the muscle layer of the bladder (stage T2 or higher) or involving the lymph nodes after surgery.
●People who could not (or chose not to) receive neoadjuvant chemotherapy that includes the drug cisplatin before cystectomy, but still have cancer extending into the layer of fat surrounding the bladder (stage T3 or higher) or involving the lymph nodes after surgery.
You may also consider enrolling in a clinical trial if possible. (See 'Clinical trials' below.)
Immunotherapy side effects — Immunotherapy can cause the body to develop an immune reaction against its own tissues. This can result in a wide range of side effects, which can occasionally be severe or life threatening, but they can be treated with medications that suppress the immune system, such as prednisone.
BLADDER PRESERVATION — In selected people with invasive bladder cancer, it may be possible to avoid removing the entire bladder. This may be an option for older adults or people with other medical problems that prevent them from being able to handle surgery. It may also be an option in healthier and younger people who prefer to keep their bladder, have good bladder function, and meet specific criteria. Your doctor can talk to you about whether you are a candidate for bladder preservation if this is something you are interested in.
The preferred option for bladder preservation is chemotherapy plus radiation (chemoradiotherapy), which is given after transurethral resection of bladder tumor (TURBT); together this is often called trimodal therapy. Other options include radical TURBT and partial removal of the bladder.
The downside of bladder-sparing procedures is that the cancer may be more likely to come back (recur) later in the bladder. This recurrence can be either non-muscle invasive, which can be treated accordingly, or muscle invasive, which would require cystectomy (surgery to remove the bladder) if the person is eligible.
Chemoradiotherapy — Chemoradiotherapy (also known as trimodal therapy [TMT]) is a treatment that involves using radiation therapy to the bladder and pelvis along with chemotherapy. Removal of all visible evidence of cancer with an extensive TURBT is recommended before proceeding to chemoradiotherapy, as this is thought to improve clinical outcomes. (See 'Transurethral resection of bladder tumor (TURBT)' below.)
Radiation therapy involves the use of focused high-energy X-rays to destroy cancer cells. The X-rays are delivered from a machine that directs the X-rays at your body. 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. Getting radiation therapy is not painful.
Chemotherapy is usually given by IV (into a vein). Chemotherapy is given at the same time or "concurrently" as radiation therapy. Chemotherapy makes the tumor cells more sensitive to the radiation treatment, improving the chance of eliminating the cancer. The combination of chemotherapy and radiation therapy is associated with improved cancer control in the bladder and pelvic region compared with radiation therapy alone. Your doctor will discuss different chemotherapy options, dosing, and potential side effects with you. (See 'Chemotherapy side effects' above.)
Transurethral resection of bladder tumor (TURBT) — TURBT is a procedure in which a physician uses a cystoscope (a thin tube with a camera) to view the lining of the bladder and remove any abnormal-appearing areas. This is similar to the procedure used to treat non-muscle invasive bladder cancer.
A radical TURBT is an aggressive procedure that goes deeper into the bladder wall, down to the layer of fat surrounding the bladder. The goal of a radical TURBT is to remove all of the cancer, while a standard TURBT may only sample the tumor in order to diagnose and stage the bladder cancer.
Several weeks after the radical TURBT, your doctor will use the cystoscope to look inside your bladder again. If there is no evidence of cancer, you will be followed closely. Radical TURBT is reserved for people who are not candidates for (or do not want) radical cystectomy or chemoradiotherapy. It is typically reserved for small tumors in a favorable location in the bladder.
If there is evidence of cancer after the radical TURBT, cystectomy to remove the bladder is usually recommended, sometimes with neoadjuvant chemotherapy before surgery. (See 'Cystectomy procedure' above.)
Partial bladder removal (partial cystectomy) — Partial cystectomy is a surgical procedure in which the tumor and some surrounding bladder tissue are removed, allowing you to keep the remaining healthy bladder. The surgery is done through a midline (up and down) incision in the lower abdomen or can be done using a robotic ("laparoscopic") technique. Removal of the involved lymph nodes should also be performed. (See 'Lymph node removal' above.)
Partial cystectomy is an option in fewer than 5 percent of people. It is typically offered to people with a single small tumor at the top of the bladder or within a bladder diverticulum (a pouch that can form in a weak part of the bladder wall). People who have recurrent bladder cancer or involvement of other areas (such as the urethra or lower bladder) are not good candidates for partial cystectomy.
The advantages of partial cystectomy are that it allows the person to urinate "normally" after surgery and does not usually interfere with sexual function. The risk of complications after surgery is much lower after partial versus radical cystectomy, and some people may be eligible for partial but not radical cystectomy. The disadvantage is that there is a higher risk of bladder cancer recurrence after partial cystectomy.
TREATMENT OF METASTATIC CANCER — Some people will develop metastatic cancer, meaning that the cancer has spread (metastasized) to other parts of the body. For patients with metastatic cancer, treatment options include chemotherapy, immunotherapy, and targeted therapy.
Chemotherapy is usually the first treatment in this situation. Immunotherapy drugs (medications that work with your immune system to attack cancer cells) are usually used after chemotherapy or if a person is not eligible for chemotherapy. Drugs that specifically target tumor cells, such as enfortumab vedotin, sacituzumab govitecan, or erdafitinib, may also be an option for some people.
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/about-cancer/treatment/clinical-trials
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Overview of the initial approach and management of urothelial bladder cancer
Clinical presentation, diagnosis, and staging of bladder cancer
Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer
Radical cystectomy
Urinary diversion and reconstruction following cystectomy
Bladder preservation treatment options for muscle-invasive urothelial bladder cancer
The following organizations also provide reliable health information:
●National Cancer Institute
(www.cancer.gov/types/bladder)
●The National Library of Medicine
(https://medlineplus.gov/bladdercancer.html)
●American Society of Clinical Oncology
(www.cancer.net/cancer-types/bladder-cancer)
●Bladder Cancer Advocacy Network
●Bladder Cancer Canada
(https://bladdercancercanada.org/en/)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Andrew J Stephenson, MD, who contributed to earlier versions of this topic review.
