Grading of bladder cancer is done by the pathologist by examination of the tumor specimen under a microscope. It is a measure of the extent by which the tumor cells differ in their appearance from normal bladder cells. Greater the distortion of appearance, the higher the grade assigned. High-grade cancers are more aggressive than low-grade ones and have a greater propensity to invade into the bladder wall and spread to other parts of the body.
In 2004, the World Health Organization developed a new grading system for bladder cancer. This system divides bladder cancers into the following groups.
Stage and grade of bladder cancer play a very important role not just in deciding the treatment that an individual patient should receive but also in quantifying the chances of success with that treatment. Of note, carcinoma in situ (CIS or Tis, as mentioned in the section on staging) is always high grade.
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.What are bladder cancer symptoms and signs?
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 best way to prevent bladder cancer is to avoid exposure to agents that cause the disease. People who don't smoke are three to four times less likely to get bladder cancer as compared to smokers. Continuing to smoke after the diagnosis of bladder cancer portends a poorer outcome and increases the chance of the disease coming back after treatment. Avoidance of occupational exposure to cancer-causing chemicals such as aniline dyes may also be important. Despite research in this area no medication or dietary supplement has been conclusively demonstrated to decrease the risk of bladder cancer in normal individuals.
