Bladder Cancer Facts . org
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"Bladder cancer Facts is an online cancer community resource center providing people living with bladder cancer a place to learn and share in a supportive, caring environment."

What is bladder cancer ?

The definition of a tumor is a mass of quickly and abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any spread. A malignant tumor is called cancer when these tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, bladder cancer occurs when cells in the lining of the bladder grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. Bladder cancers arise almost exclusively from the lining of the bladder. In the United States, 98% of bladder cancers are called transitional cell carcinomas. This simply means that the cancer started in the lining of the bladder, which is made up of transitional cells that appear elliptical under the microscope.

Less commonly are other types of cancers that arise from the lining of the bladder, called adenocarcinomas, squamous cell carcinomas and small cell carcinomas. A common way for bladder cancers to grow is called a papillary growth pattern. When a bladder cancer grows this way, it can be noninvasive, i.e., not invading into tissues at all, and hence not having a risk for distant spread (as long as it is treated).

In addition to other invasive cancers, patients are sometimes diagnosed with precancerous lesions, called carcinoma-in-situ. Carcinoma-in-situ occurs when the lining of the bladder undergoes changes similar to cancerous changes without any invasion into the deeper tissues. Hence, while the cells themselves have cancer-like qualities, there is no risk of spread, as no invasion has occurred. However, both papillary bladder cancers and cancer-in-situ may become invasive and cause problems if not treated.

 

Am I at risk for bladder cancer ?

Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women. Over 50,000 cases are diagnosed every year in the United States, with over 12,000 deaths. Internationally, the incidence of bladder cancer varies substantially, with highest rates in Europe and North America and in areas (Northern Africa) endemic with a type of fluke called Schistosoma haematobium, which induces a predominance of squamous cell carcinomas. Classically, bladder cancer is thought of as a disease that affects older men, with men affected more than women by a 3:1 ratio and 2/3 of the cases diagnosed in people over the age of 65.

Cigarette smoking is the largest risk factor for bladder cancer (yet another reason to stop smoking). Smokers have 2-4 times the risk of having bladder cancer, and it contributes to up to 50% of all bladder cancers that are diagnosed. Other than the previously mentioned Schistosoma haematobium infections, the only other risk factors known are from occupational exposures, such as polychromatic hydrocarbons (benzene, benzidine). More recently, an association has been made between chlorinated drinking water and bladder cancer. Though there have been suggestions of saccharin and high intake of dietary fat and cholesterol being causative for bladder cancer, these have yet to be substantiated.

 

How can I prevent bladder cancer ?

Smoking is the strongest risk factor associated with the development of bladder cancer. Therefore, smoking cessation is the best way to prevent bladder cancer. Also, obviously reducing the exposure to carcinogenic compounds should decrease the risk of developing bladder cancer. Other than these preventative measures, decreasing the risk of bladder cancer relies on early detection of symptoms and possibly screening high-risk individuals.

 

What screening tests are available?

The goals of screening tests are to detect cancers early and initiate treatment when the cancer is in an early stage, or even before it becomes invasive. Cytologic examination of urine (looking for abnormal cells in urine) has been the most commonly tested screening tool. It involves testing urine for the presence of abnormal cells, which would indicate the possibility of a cancer.

This method is fairly inexpensive and without risk to the patient. If abnormal cells are seen, over 95% of the time it accurately predicts the presence of bladder cancer. However, a fair amount of cancers can be missed using this method. Also, the incidence of preclinical (too small to cause any symptoms) bladder cancer in the general population is likely too low for cytologic examination of urine to be useful as a mass screening tool.

Routine examination of the urine for the detection of blood (by far the most common presentation of bladder cancer) has also been tested and also appears to be inadequate for mass screening. Therefore, there is no tried screening method for bladder cancer, so the best method for detecting bladder cancer and preventing an aggressive bladder cancer is to not smoke or stop smoking and to not ignore the symptoms of bladder cancer, which usually involves blood noted in the urine.

 

What are the signs of bladder cancer ?

By far the most common sign of bladder cancer is the presence of blood in the urine, called hematuria. The blood in the urine can either be noticeable by the naked eye, called gross hematuria, or noted only when the urine is analyzed in a laboratory, called microscopic hematuria. Either gross hematuria or microscopic hematuria is present in over 80% of cases of bladder cancer. Therefore, when someone is noted to have blood in the urine, it must be proven to be something other than bladder cancer.

Other signs of bladder cancer could include symptoms of a urinary tract infection. These include increased frequency of urination, a feeling of urgency to urinate, pain (burning) with urination, and the feeling of incomplete bladder emptying. These are all caused by irritation of the bladder wall by the tumor.

In advanced cases of bladder cancer, the tumor can actually obstruct either the entrance of urine into the bladder or the exit of urine from the bladder. This causes severe flank pain, infection, and damage to the kidneys. Obviously, bladder cancers that cause these symptoms need to be dealt with immediately.

 

How is bladder cancer diagnosed and staged?

 

Diagnosis

Anyone with either gross or microscopic hematuria should undergo a work-up to insure the symptoms are not from bladder cancer. Often, the first thing that is done is a urine cytology, which as mentioned above, is looking at the urine under a microscope to detect cancerous appearing cells. Again, if these cells are seen, it is diagnostic. However, the test does not detect all cases of bladder cancer. If bladder cancer is highly suspected, or after diagnosis, X-ray imaging of the upper urinary tract (including the ureters and kidneys) is done, to rule out any involvement of these structures with cancer.

Ultrasound can be used to study the kidneys and a CT scan is often very good at studying the entire length of the urinary tract. A simpler method of studying the (upper) urinary tract is with an intravenous pyelogram (IVP). This involves administering a dye through a patient's vein and taking a regular x-ray a short time later. The dye can be seen in the x-ray, showing the full extent of the kidney collecting system, ureters, and often the bladder.

Though the above tests are useful or even required, the mainstay of diagnosis and staging is endoscopic evaluation. In this case, this type of evaluation is called a cystoscopy. It involves placing a fiber optic camera into the bladder via the urethra. Cystoscopy allows for direct visualization of the entire bladder and also allows for biopsy for any suspicious lesions. If the biopsy reveals cancer, a repeat cystoscopy and resection (called a transurethral resection (TUR)) is done to completely evaluate the tumor and the extent and depth of disease.

With a diagnosis of bladder cancer obtained, a complete physical examination is done as well as the previously mentioned radiologic studies to fully evaluate the urinary tract, the local extent of disease, and any metastatic disease.

Staging

The staging of a cancer basically describes how much it is grown before the diagnosis has been made, documenting the extent of disease. Bladder cancer often presents at an early stage, as it produces hematuria early on in the course of the disease. Unfortunately, sometimes bladder cancer can advance to invasive disease prior to causing symptoms. As will be discussed in the treatment section, a big distinction is whether the bladder cancer is superficial or invading into the muscle, because the treatments are much different. Before the staging systems are introduced, first some background on how cancers grow and spread, and therefore advance in stage.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. Bladder cancers often start very superficial, involving only the lining of the bladder. Eventually, however, bladder cancers can invade into the bladder, involving the muscular layers of the wall. If the bladder cancer is allowed to grow long enough or is aggressive enough, it may eventually invade the entire way through the wall and into the fat surrounding the bladder or even into other organs (prostate, uterus, vagina). This local extension is the most common way bladder cancer spreads.

Cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Bladder cancer can spread this way. If it does, it usually first spreads to the lymph nodes surrounding the bladder (perivesicular lymph nodes). From there, it can spread to lymph nodes that are in close proximity to the external iliac and internal iliac arteries and veins, which are the very large blood vessels that run into the leg and into pelvis, respectively. The presence of lymph node spread is best evaluated by CT scan or at surgical exploration.

Bladder cancer can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from cells' travel to other organs are called metastases. Cancers of the bladder generally spread locally or to lymph nodes before spreading distantly through the bloodstream, though this is not always the case. If spread through the bloodstream does occur, the lungs and bones are the most common sites to be involved.

The staging system used to describe bladder tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the throat itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

There are two "T" stages that are often reported: the clinical stage, which is based on the physical exam of the physician, and the pathologic stage, which is noted after the tumor is resected, or taken out surgically.

Clinical Staging

• T1-Physician feels nothing on exam prior to transurethral resection (TUR)
• T2-Physician feels nothing on exam after TUR
• T3a-Any visually incomplete TUR or persistent tumor felt after TUR
• T3b-Any tumor that extends beyond bladder on exam
• T4-Tumor that involves other organs

Pathologic Staging

• Ta-noninvasive papillary tumor
• Tis-carcinoma-in-situ (explained above)
• T1-tumor invading the mucosa (lining of bladder)

Above are considered "superficial"

• T2-tumor invades superficially into muscle of wall
• T3a-tumor invades deeply into muscle of the bladder wall
• T3b-tumor invades the entire way through the wall
• T4-tumor invades other organs

The "N" stage is as follows:

• N0-no spread to lymph nodes
• N1-tumor spread to a single lymph node, but this tumor spread must be less than 2 cm
• N2-tumor spread to lymph nodes sized 2-5 cm
• N3-tumor spread to lymph nodes greater than 5 cm

The "M" stage is as follows:

• M0-no tumor spread to other organs
• M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters. Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed. An important distinction in bladder cancer is between superficial disease (Ta, Tis, T1) or muscular invasive disease. It has large implications for treatment, as will be discussed below.

 

 

What are the treatments for bladder cancer ?

 

 

Superficial Bladder Cancer

Superficial bladder cancer is that which has not invaded at all into the muscle. As noted above, the extent of disease is based mainly on the transurethral resection (TUR). Likewise, the primary treatment for superficial disease is the TUR. Given the fact that the cancer is superficial, all of the tumor should be able to be removed by the TUR. However, superficial bladder cancer has a high incidence of recurrence, and hence the goal of treatment switches to the prevention of these recurrences and to prevent progression to an invasive stage.

The treatment of a superficial bladder cancer always involves TUR. In high grade tumors, large tumors, multiply recurrent superficial tumors, or any tumor that invades into the lining of the bladder (T1 tumors), additional agents are infused directly into the bladder to help to decrease recurrences. The most commonly used is a compound that causes an inflammatory reaction, called BCG. BCG is instilled directly into the bladder for several treatments over several months.

Though other agents have also been used, BCG has the best results, decreasing recurrence rates and progression rates in patients with superficial cancers. Though BCG is successful, it is not without side effects-causing bladder spasm and irritation, often with every instillation.

Muscle Invading Bladder Cancer

The standard of care in treating more advanced cancers has always involved surgically removing the entire bladder in a procedure called a cystectomy. A large concern in performing this surgery is how to divert the urine so that the patient can still excrete it. In the past, this was done using an "ileal conduit", where the urine drained through a portion of the small intestine and out through the skin into a bag.

More recently, techniques creating new bladders have been used. This allows the ureters to be implanted into the newly created bladder and the urethra to lead out of the new bladder. In the right surgical hands, the patient can continue to have very high rates of continence. In addition to cystectomy, superior results have been demonstrated by using chemotherapy, either before the surgery or after the surgery.

Though trials using chemotherapy in addition to surgery have not demonstrated an overall survival benefit, they have shown decreased bladder cancer rates. With this, and evidence that many patients have metastases at presentation that cannot be detected, most physicians recommend some type of chemotherapy to go along with surgery.

An alternative to cystectomy that has been advocated recently is using a combination of chemotherapy and radiation to spare the patient of a significant surgical procedure. Regimens that have the best results all start with maximum resection of the bladder tumor via TUR, just like with superficial bladder cancers.

The patient then starts a treatment course of radiation with chemotherapy (usually with the chemotherapy drug cisplatin) for 4-5 weeks. Patients are then reevaluated by a repeat cystoscopy procedure to determine if the chemotherapy and radiation had made the tumor completely disappear. If the tumor is gone by examination, further chemotherapy and radiation is given for an additional 2-3 weeks.

This method has comparable survival rates to cystectomy and has the advantage of allowing the patient to keep his or her bladder, and subsequently, continence. Again, though, there are side effects of this treatment. The most concerning of these are decreased bladder capacity (leading to more frequent urination), bladder spasm, and perhaps chronic burning or pain with urination, or hematuria from the damage done by the chemotherapy and radiation.

Overall, there are different treatment methods available for bladder cancer. All have curative potential. Like many other sites of cancer, there has been a development of regimens that allow for a higher quality of life after the treatment is completed.

The exact method of treatment should be chosen individually by the patient, after discussing it with a team of physicians adept at treating bladder cancer, to maximize chance of cure and function. Obviously the best treatment for cancer is prevention of ever developing cancer. By far, the best prevention is not smoking or immediate smoking cessation.