Bladder cancer is an uncontrolled abnormal growth and multiplication of cells in the urinary bladder which have broken free from the normal control mechanisms of the body. Bladder cancer (like cancers of other organs) has the ability to spread (metastasize) to other body parts including the lungs, bones, and liver.
Bladder cancer invariably starts from the innermost layer of the bladder (for example, the mucosa) and may invade into the deeper layers as it grows. Alternately, it may remain confined to the mucosa for a prolonged period of time.
Visually, it may appear in various forms. Most common is a shrub-like appearance (papillary) but it may also appear as a nodule, an irregular solid growth or a flat, barely perceptible thickening of the inner bladder wall (details in subsequent sections).
The most common symptom of bladder cancer is bleeding in the urine (hematuria). Most often the bleeding is "gross" (visible to the naked eye), episodic (occurs in episodes), and is not associated with pain (painless hematuria). However, sometimes the bleeding may only be visible under a microscope (microscopic hematuria) or may be associated with pain due to the blockage of urine by formation of blood clots.
There may be no symptoms or bleeding for prolonged periods of time between episodes, lulling the patient into a false sense of security ("I don't know what the problem was, but it is fine now!"). Some types of bladder cancer may cause irritative symptoms of the bladder with little or no bleeding.
The patients may have the desire to urinate small amounts in short intervals (frequency), inability to hold the urine for any length of time after the initial desire to void (urgency), or burning sensation while passing urine (dysuria). These symptoms occur more commonly in patients with high-grade, flat urothelial cancers called "carcinoma in situ" or "CIS" (described subsequently in the section on staging of bladder cancer).
Rarely, patients may present with signs and symptoms of more advanced disease such as a distended bladder (due to obstruction by a tumor at the bladder neck), pain in the flanks (due to obstruction of urine flow from kidney to the bladder by the growing tumor mass in the bladder), bone pains, or cough/blood in the phlegm (due to spread to cancer cells to bones or lungs).
The most common type of bladder cancer, urothelial carcinoma, is very strongly associated with cigarette smoking. About 50% of all bladder cancers in men and 30% in women may be caused by cigarette smoking. The longer and heavier the exposure, greater are the chances of developing bladder cancer.
The toxic chemicals in cigarette smoke, many of which are known cancer causing substances (carcinogens), travel in the bloodstream after being absorbed from the lungs and get filtered into the urine by the kidneys. They then come in contact with the cells in the inner lining of the urinary system, including the bladder, and cause changes within these cells which make them more prone to developing into cancer cells.
Quitting smoking decreases the risk of developing bladder cancer but takes many years to reach the level of people who have never smoked. However, as time passes after the quit date, the risk progressively decreases. In view of the above, it is extremely important for patients with bladder cancer to stop smoking completely since the chances of the cancer coming back after treatment are higher in those people who continue to smoke.
People who smoke also have a higher risk of many other types of cancer, including leukemia and cancers of the lung, lip, mouth, larynx, esophagus, stomach, and pancreas. Smokers also have a higher risk of diseases like heart attacks, peripheral vascular disease, diabetes, stroke, bone loss (osteoporosis), emphysema, and bronchitis.
Age and family history are other risk factors as is male sex. Most bladder cancer is diagnosed in people over 60 years though in exceptional cases it may be seen in the third or fourth decade of life. Men are more prone to developing bladder cancer probably due to a higher incidence of smoking and exposure to toxic chemicals. A close relative with a history of bladder cancer may increase the predisposition for the development of this disease.
Exposure to toxic chemicals such as arsenic, phenols, aniline dyes, and arylamines increase the risk of bladder cancer and may be responsible for up to 25% of cases in some regions. Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk.
Radiation therapy (such as that for prostate or cervical cancer) and chemotherapy with cyclophosphamide (Cytoxan) has been shown to increase the risk for development of bladder cancer.
Moreover, it may also delay the diagnosis of bladder cancer in patients presenting with symptoms of bleeding in urine since this bleeding may be incorrectly attributed by the patient and/or the physician to the bladder irritation caused by the chemotherapy or radiation (radiation cystitis).
Long-term chronic infections of the bladder, irritation due to stones or foreign bodies, and infections with the blood fluke prevalent in certain regions of the world (as mentioned earlier) are some other factors which predispose to bladder cancer.
The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope. Immunotherapy in the form of BCG instillation is also used to treat and prevent the recurrence of superficial tumors.
BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy, such as valrubicin (Valstar) into the bladder can also be used to treat BCG-refractory CIS disease when cystectomy is not an option.Urocidin is phase III trials for this.
Patients whose tumors recurred after treatment with BCG are more difficult to treat. Many physicians recommend Cystectomy for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU) and the American Urological Association (AUA).
However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort.
Device assisted chemotherapy is such one group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology uses an electrical current to enhance drug absorption.
Another technology, Thermo-chemotherapy, uses radio-frequency energy to directly heat the bladder wall. The heat and chemotherapy show a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.
Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (acystectomy) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.
A combination of radiation and chemotherapy can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.
There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statins is associated with failure of BCG immunotherapy.
Photodynamic diagnosis may improve surgical outcome on bladder cancer.