Bladder Cancer in Men

Bladder cancer is one of the most common cancers, affecting approximately 68,000 adults in the United States each year. Bladder cancer occurs in men more frequently than it does in women and usually affects older adults, though it can happen at any age.

Bladder cancer most often begins in the cells (urothelial cells) that line the inside of your bladder — the hollow, muscular organ in your lower abdomen that stores urine. Although it’s most common in the bladder, this same type of cancer can occur in other parts of the urinary tract drainage system.

The most common type of bladder cancer in the United States and western Europe is urothelial carcinoma, also known as transitional cell carcinoma (TCC). Other types of bladder cancer are also found occasionally, including squamous carcinoma (which resembles skin cancer under the microscope) and adenocarcinoma (which has a glandular pattern, similar to bowel cancer, under the microscope).

In other areas of the world, such as the Northern African and Mediterranean regions, squamous carcinoma may be seen more often in areas where schistosomiasis is endemic, although urothelial cancer (TCC) remains the most common tumor there as well.

Risk Factors

Factors that may increase bladder cancer risk include:

• Smoking — Smoking cigarettes, cigars or pipes may increase the risk of bladder cancer by causing harmful chemicals to accumulate in the urine. When you smoke, your body processes the chemicals in the smoke and excretes some of them in your urine. These harmful chemicals may damage the lining of your bladder, which can increase your risk of cancer.
• Increasing age — Bladder cancer risk increases as you age. Bladder cancer can occur at any age, but it’s rarely found in people younger than 40.
• Being white — White people have a greater risk of bladder cancer than do people of other races.
• Being a man — Men are more likely to develop bladder cancer than women are.
• Exposure to certain chemicals — Your kidneys play a key role in filtering harmful chemicals from your bloodstream and moving them into your bladder. Because of this, it’s thought that being around certain chemicals may increase the risk of bladder cancer. Chemicals linked to bladder cancer risk include arsenic and chemicals used in the manufacture of dyes, rubber, leather, textiles and paint products.
• Previous cancer treatment — Treatment with the anti-cancer drug cyclophosphamide increases the risk of bladder cancer. People who received radiation treatments aimed at the pelvis for a previous cancer have an elevated risk of developing bladder cancer.
• Chronic bladder inflammation — Chronic or repeated urinary infections or inflammations (cystitis), such as might happen with long-term use of a urinary catheter, may increase the risk of a squamous cell bladder cancer. In some areas of the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis.
• Personal or family history of cancer — If you’ve had bladder cancer, you’re more likely to get it again. If one of your first-degree relatives i.e., a parent, sibling or child has a history of bladder cancer, you may have an increased risk of the disease, although it’s rare for bladder cancer to run in families. A family history of hereditary nonpolyposis colorectal cancer, also called Lynch syndrome, can increase the risk of cancer in the urinary system, as well as in the colon, uterus, ovaries and other organs.

Symptoms

Blood in the urine (hematuria) is the most common symptom of bladder cancer. It is generally painless. Often, you cannot see blood in your urine without a microscope. If you can see blood with your naked eye you should tell your healthcare provider immediately. Even if the blood goes away, you should still talk to your doctor about it.

Blood in the urine does not always mean that you have bladder cancer. There are a number of reasons why you may have blood in your urine. You may have an infection or kidney stones. Very small amounts of blood might be normal in some people.

Frequent urination and pain when you pass urine (dysuria) are less common symptoms of bladder cancer. If you have these symptoms, it’s important to see your healthcare provider. Your provider will find out if you have a urinary tract infection or something more serious, like bladder cancer.

Evaluation and Diagnosis

Anyone who has signs or symptoms of bladder cancer should have a complete evaluation of the kidneys, ureters, bladder, and urethra, especially if the person is greater than 35 years old. This evaluation includes one or more urine tests, cystourethroscopy, and an imaging test of the kidneys and ureters.

Urine Tests

Several urine tests may be recommended in people with bladder symptoms.

• Urinalysis is a test that uses a chemical dipstick that changes color in response to the presence of certain features in the urine, such as white blood cells, red blood cells, and glucose (sugar). The urine is also examined with a microscope.
• Urine cytology is a test in which an experienced pathologist examines a sample of urine with a microscope to see if there are abnormal-appearing cells shed from the lining of the urethra, bladder, ureters, and kidneys. A pathologist can often identify whether abnormal cells are actually cancerous.

Imaging Tests

Imaging tests can help to detect any masses or abnormalities in the kidneys, ureters, bladder, or urethra. The optimal imaging test e.g., computed tomography (CT) scan, magnetic resonance imaging (MRI), intravenous pyelogram (IVP), or kidney ultrasound depends upon the individual situation.

• CT scan — CT scan is an imaging test that examines the structure of the kidneys, ureters, and bladder. The CT scan can show the extent of a cancer, determine if there is a blockage in the urinary tract, and determine if the cancer has spread outside the bladder. CT scans usually require the use of contrast dye.
• MRI — Multiparametric MRI of the kidney, ureters, and bladder has been utilized to evaluate the urinary tract. This imaging may provide additional information in staging bladder cancer and can be used in patients with allergies to contrast dye.
• IVP — In an IVP, a radiopaque dye (one that is seen on x-ray) is injected into a vein. The dye collects in and is excreted by the kidneys. As the dye passes through the kidney and into the bladder, the urinary tract and any masses are visible on x-ray.

Cystoscopy

Cystoscopy, also called cystourethroscopy, is a procedure that is done to examine the lining of the urethra and bladder. It can be done by a urologist in an office setting or in an operating room. When performed in the office, a numbing gel is applied to the urethra to decrease discomfort. A small tube with a camera (cystoscope) is then inserted into the bladder through the urethra.

Biopsy

During cystoscopy, your doctor may pass a special tool through the scope and into your bladder to collect a cell sample (biopsy) for testing. This procedure is sometimes called transurethral resection of bladder tumor (TURBT). TURBT can also be used to treat bladder cancer.

Cancer Grading

A cancer’s grade refers to how the cancer cells appear under the microscope. Grade is one factor used to predict how likely the cancer is to recur after treatment and, ultimately, the person’s chance of surviving his or her cancer. Bladder tumors are classified as either low or high grade.

• Low-grade bladder tumor — This type of tumor has cells that are closer in appearance and organization to normal cells (well-differentiated). A low-grade tumor usually grows more slowly and is less likely to invade the muscular wall of the bladder than is a high-grade tumor.
• High-grade bladder tumor — This type of tumor has cells that are abnormal-looking and that lack any resemblance to normal-appearing tissues (poorly differentiated). A high-grade tumor tends to grow more aggressively than a low-grade tumor and may be more likely to spread to the muscular wall of the bladder and other tissues and organs.

Cancer Staging

A staging system is a standard way to describe how far a cancer has spread. The staging system most often used for bladder cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

• T describes how far the main (primary) tumor has grown through the bladder wall and whether it has grown into nearby tissues.
• N indicates any cancer spread to lymph nodes near the bladder. Lymph nodes are bean-sized collections of immune system cells, to which cancers often spread first.
• M indicates whether or not the cancer has spread (metastasized) to distant sites, such as other organs or lymph nodes that are not near the bladder.

Numbers or letters appear after T, N, and M to provide more details about each of these factors. Higher numbers mean the cancer is more advanced.

The T category describes how far the main tumor has grown into the wall of the bladder (or beyond).

The wall of the bladder has 4 main layers. The innermost lining is called the urothelium or transitional epithelium. Beneath the urothelium is a thin layer of connective tissue, blood vessels, and nerves. Next is a thick layer of muscle. Outside of this muscle, a layer of fatty connective tissue separates the bladder from other nearby organs.

Nearly all bladder cancers start in the urothelium. As the cancer grows into or through the other layers in the bladder, it becomes more advanced. The T stages are defined as follows:

• TX — Main tumor cannot be assessed due to lack of information
• T0 — No evidence of a primary tumor
• Ta — Non-invasive papillary carcinoma
• Tis — Non-invasive flat carcinoma (flat carcinoma in situ, or CIS)
• T1 — The tumor has grown from the layer of cells lining the bladder into the connective tissue below
• T2 — The tumor has grown into the muscle layer
• T3 — The tumor has grown through the muscle layer of the bladder and into the fatty tissue layer that surrounds it
• T4 — The tumor has spread beyond the fatty tissue and into nearby organs or structures

The N category describes spread only to the lymph nodes near the bladder (in the true pelvis) and those along the blood vessel called the common iliac artery. These lymph nodes are called regional lymph nodes. Any other lymph nodes are considered distant lymph nodes.

Surgery is usually needed to find cancer spread to lymph nodes, since it is not often seen on imaging tests. Spread to distant nodes is considered metastasis (described in the M category). The N stages are defined as follows:

• NX — Regional lymph nodes cannot be assessed due to lack of information
• N0 — There is no regional lymph node spread
• N1 — The cancer has spread to a single lymph node in the true pelvis
• N2 — The cancer has spread to 2 or more lymph nodes in the true pelvis
• N3 — The cancer has spread to lymph nodes along the common iliac artery

The M stages are defined as follows:

• M0 — There are no signs of distant spread
• M1 — The cancer has spread to distant parts of the body

Treatment

The optimal treatment for urothelial bladder cancer depends upon the cancer’s stage and grade. Approximately 70 percent of all new cases of bladder cancer are classified as non-muscle-invasive, also called superficial bladder cancer. The initial treatment for this stage of bladder cancer is surgical removal of the tumor through a cystoscope called transurethral resection of bladder tumor (TURBT). This is often followed by adjuvant (additional) therapy, which reduces the chances of the cancer recurring.

Of these, approximately 20 to 25 percent of initially non-muscle-invasive cancers will progress to invasive types during the person’s lifetime.

The remaining 30 percent of bladder cancers are muscle invasive and generally require surgery to remove the bladder (cystectomy) and the surrounding organs.

Non-Muscle Invasive Bladder Cancer (NMIBC)

Surgery is part of the treatment for most bladder cancers. The type of surgery used depends on the stage (extent) of the cancer.

Transurethral resection of bladder tumor (TURBT), also known as just a transurethral resection (TUR), is often used to determine if someone has bladder cancer and, if so, whether the cancer has invaded the muscle layer of the bladder wall.

This is also the most common treatment for early-stage or superficial (non-muscle invasive) bladder cancers. Most patients have superficial cancer when they are first diagnosed, so this is usually their first treatment. Some people might also get a second, more extensive TURBT as part of their treatment.

TURBT is a procedure in which a physician uses a cystoscope to see inside the bladder and remove any abnormal-appearing areas. A cystoscope is a long, thin tube that contains a light and a camera.

In most cases, this procedure is done in an operating room while the person is under anesthesia. After the procedure, you can usually go home, sometimes with a catheter for a few days.

In certain cases, usually in people with more aggressive microinvasive cancers, a second TURBT will be performed several weeks after the first to be sure that no tumor was missed during the original cystoscopy. If all tumor has been removed after this second TURBT, you will begin adjuvant therapy.

Adjuvant bladder cancer therapy — Even in people who have their bladder tumor completely removed with transurethral resection of bladder tumor (TURBT), up to 50 percent will have a recurrence of their cancer within 12 months. Because of this high recurrence rate, adjuvant (additional) therapy is usually recommended. The type of adjuvant therapy recommended depends upon your risk of recurrence.

Some people who are at low risk of recurrence will be advised to have a single dose of intravesical chemotherapy at the time of the initial TURBT. This is thought to help prevent floating tumor cells dislodged from the TURBT from seeding and starting new tumors. “Intravesical” means that the treatment is put inside of the bladder, usually through a catheter (a flexible tube passed through the urethra, where urine exits). This allows a high concentration of the treatment to be applied directly to the areas where tumor cells could remain, potentially destroying these cells and preventing them from re-emerging in the bladder and forming new tumors.

Some people who are at intermediate risk of recurrence will be advised to have either a full six-week course of intravesical chemotherapy, most commonly mitomycin or epirubicin, or intravesical immunotherapy with Bacillus Calmette-Guerin (BCG). Both kinds of therapy usually involve additional booster treatments for up to one year (maintenance therapy).

People at high risk of recurrence or worsening will be advised to start intravesical BCG, usually within two to six weeks of the first treatment. This is most commonly followed by additional booster treatments (maintenance therapy) once a complete response is obtained. Occasionally, however, patients are advised to consider bladder removal (cystectomy), especially if the disease is extensive.

Intravesical chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. The most commonly used intravesical chemotherapy for bladder cancer is mitomycin. This is put inside the bladder in one of two ways:

1. One regimen involves giving the mitomycin once, immediately after TURBT. The solution is left in the bladder for 60 minutes, then allowed to drain out through a catheter.
2. Alternatively, the mitomycin can be given on a weekly basis for six weeks. With this regimen, the bladder is filled with mitomycin through a catheter, the solution is left for one to two hours, and then the drug is drained through the catheter. Maintenance treatment may be given once per month for up to one year.

Side effects — Mitomycin often causes temporary irritation of the bladder, including the need to urinate frequently and urgently and pain with urination. Mitomycin can also cause a skin rash on the palms of the hands, soles of the feet, and genitals. If this rash occurs, treatment with mitomycin is stopped and should not be restarted. Occasionally, cortisone therapy is prescribed if the effects are severe and not resolving on their own. A different chemotherapy drug, or even BCG, might be substituted in this situation. Rarely, mitomycin can cause the bladder to shrink down so that it holds less urine.

Intravesical BCG — BCG is an attenuated live bacterium that causes cow tuberculosis. It is a common treatment for non-muscle invasive bladder cancer, particularly for cancers that have a risk of worsening over time. BCG is believed to work by triggering the body’s immune system to destroy any cancer cells that remain in the bladder after TURBT.

BCG is in a liquid solution that is put into the bladder with a catheter. The person then holds the solution in the bladder for two hours before they urinate. The treatment is usually given once per week for six weeks, starting approximately three to six weeks after the last TURBT. Further booster (maintenance) treatments can extend the benefits of BCG.

Benefits of intravesical BCG — Intravesical BCG, in combination with TURBT, is the most effective treatment for non-muscle invasive bladder cancer. BCG therapy has been shown to delay tumor growth to a more advanced stage and decrease the need for surgical removal of the bladder at a later time.

Side effects of BCG — Most people who are treated with intravesical BCG have some side effects; the most common of these include the need to urinate frequently, pain with urination, fever, blood in the urine, and body aches. These symptoms usually begin within two to four hours of treatment and resolve within 48 hours.

Anyone who develops a fever (temperature greater than 100.4ºF or 38ºC) and drenching night sweats 48 hours or more after treatment with BCG should contact their health care provider. These may be signs of less common but more serious side effects, including body wide infection.

Testing After Initial Bladder Cancer Treatment

Tests are usually performed approximately three months after the start of intravesical treatment, or transurethral resection of bladder tumor (TURBT) for those who did not get intravesical therapy, to be sure that the cancer has not recurred. If there are no signs of recurrence, maintenance Bacillus Calmette-Guerin (BCG) treatment may be recommended.

If there are signs of cancer recurrence, any abnormal areas will be biopsied and removed with TURBT. Treatment after TURBT will depend upon the tumor’s stage at recurrence and the amount of time that has passed since the first course of BCG was given. In general, there are two options: further treatment with weekly intravesical therapy or surgical removal of the bladder (cystectomy).

Maintenance BCG — Maintenance intravesical BCG treatment is generally recommended for patients with high-risk non-muscle invasive bladder cancer. The benefit of maintenance treatment is that it may further delay recurrence and progression of the cancer.

Although the optimal duration of maintenance treatment is debated, several expert groups recommend that it be given for at least one year. Maintenance BCG is typically given once per week for three weeks at 3, 6, and 12 months after the initial BCG treatment. In some cases, maintenance BCG treatment will be recommended for one year for those at intermediate risk of recurrence and for three years for those at higher risk for recurrence.

Surveillance After Bladder Cancer Treatment

Even in people who are treated appropriately, bladder cancer often recurs. Recurrent cancer can develop anywhere along the urinary tract, including the lining of the kidneys, ureters, prostate, urethra, and bladder. Close follow-up after treatment is required to monitor for recurrence.

Cystoscopy and urine cytology — Repeat cystoscopy and urine cytology testing are recommended for surveillance, beginning three months after treatment ends. If there are no signs of recurrence, cystoscopy and urine testing are usually recommended every three to six months for four years, then once per year. Low-risk patients require less frequent cystoscopy and no urine cytology testing.

If there are signs of recurrent bladder cancer, the next step depends upon several factors, including the person’s age and underlying medical problems, the tumor’s stage and grade at recurrence, previous treatments used, and the amount of time that has passed since the last course of treatment. In general, the options include a second course of intravesical therapy, e.g., repeat Bacillus Calmette-Guerin (BCG), BCG/interferon, valrubicin, or gemcitabine or surgical removal of the bladder (cystectomy).

Imaging tests — The upper urinary tract (e.g., kidneys, ureters) is lined with the same cells as the bladder. The tumors that develop in the bladder can develop in the upper urinary tract as well. As a result, an imaging test, such as a computed tomography (CT) scan, is recommended before and sometimes after the initial course of treatment. This type of test is usually done every one to two years for patients with higher-risk tumors.

Muscle Invasive Bladder Cancer (MIBC)

The best treatment for muscle invasive bladder cancer depends on the stage of the cancer as well as a person’s age, health, other medical conditions, and personal preference. The standard treatment for muscle invasive bladder cancer includes surgery to remove the bladder (called radical cystectomy). Radical cystectomy requires the creation of a new way to get rid of urine.

In some cases, it is possible to avoid cystectomy by having a bladder-sparing treatment. However, this treatment is an option only for a small number of people with muscle invasive bladder cancer, due to the high risk that the cancer will come back (recur).

For people with muscle invasive bladder cancer who are able to tolerate more aggressive treatment, chemotherapy is often given before or, in some cases, after surgery.

Cystectomy — Cystectomy includes removal of the bladder, the nearby organs, and the associated lymph nodes. This procedure is also called “radical” cystectomy.

In men, radical cystectomy generally includes removal of the bladder as well as the prostate and seminal vesicles. 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 to enable men to preserve the potential of recovering sexual function in certain situations.

In women, radical cystectomy usually involves removal of the bladder as well as the ovaries, uterus, cervix, and upper vagina.

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 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 used to create the urinary diversion. Possible urinary diversion options include:

Ileal conduit — 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.

Continent cutaneous diversion — A reservoir (like a pouch) may be created under the skin of the abdomen using tissue from the intestines. Urine collects in the pouch, and you use a catheter (a thin tube) to empty the pouch periodically. It is not necessary to wear a bag.

Orthotopic neobladder — 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 the person to urinate normally.

The “ideal” type of urinary diversion depends on your and your surgeon’s preference as well as the extent of your cancer. The reservoir and neobladder may 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. The risk of each of these depends on which type of urinary diversion is performed.

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. In some instances, chemotherapy may be given after surgery instead (“adjuvant”).

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. 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. Regimens usually include a drug called cisplatin along with one or more other drugs. The drugs are given intravenously (by IV) over three to four cycles.

Adjuvant chemotherapy — “Adjuvant” in this case means chemotherapy that is after surgery. In some situations, chemotherapy is not given before cystectomy. However, for these people, chemotherapy may be recommended after surgery 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: 1) the tumor extends into the layer of fat surrounding the bladder (stage T3 or higher) or 2) cancerous cells are identified in the lymph nodes that were removed during the cystectomy.

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, 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.

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 people who are elderly or have other medical problems that prevent them from being able to handle surgery. It may also be an option in certain situations if a person prefers to keep their bladder, has good bladder function, and has a single tumor that meets specific criteria. Bladder preservation options include:

Chemoradiotherapy — Chemoradiotherapy is a treatment that involves using radiation therapy to the bladder and pelvis along with chemotherapy. Removal of all visible evidence of cancer with transurethral resection of bladder tumor (TURBT) is recommended before proceeding to chemoradiotherapy. Chemoradiotherapy is less likely to be successful in people who still have evidence of 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 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. A chemotherapy drug is usually given once every three weeks into a vein during 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.

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 superficial bladder cancer.

However, radical TURBT is 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. 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. If there is evidence of cancer after the radical TURBT, cystectomy to remove the bladder is usually recommended, sometimes with neoadjuvant chemotherapy before surgery.

Partial bladder removal (Partial cystectomy) — Partial cystectomy is a surgical procedure in which the bladder tumor and some surrounding bladder tissue are removed, allowing you to keep the remaining healthy bladder. Removal of the involved lymph nodes is also performed.

Partial cystectomy is not an option for the vast majority of most people, but it may be available for people with certain characteristics, including 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 disadvantage is that there is a higher risk of bladder cancer recurrence after partial cystectomy.