Bladder cancer imaging.(CE DIRECTED READING)

After completing this article, readers should be able to:

* Cite risk factors associated with bladder cancer:

* Describe the normal anatomy and physiology of the urinary bladder.

* List the clinical signs and symptoms of bladder cancer.

* Summarize the diagnostic imaging technologies available for bladder cancer.

* Describe the staging and treatment options for bladder cancer.

Bladder cancer consists of the uncontrolled multiplication and growth of abnormal cells in the tissues that compose the urinary bladder. A common site of growth is on the internal surface of the urinary bladder. However, bladder cancer also can spread into the various layers of tissue composing the urinary bladder. The disease typically affects older people, and almost 90% of bladder cancers are found in people 55 years or older. (1)

The American Cancer Society (ACS) estimated that approximately 67 000 new cases of urinary bladder cancer were diagnosed in the United States in 2007. The incidence of bladder cancer has been increasing since the 1950s, and the National Cancer Institute (NCI) reported that the trend of increasing incidence will continue due to the aging of the U.S. population.' Fortunately, mortality rates have been decreasing, as will be discussed in a subsequent section.

This Directed Reading will review the epidemiology of and risk factors associated with urinary bladder cancer. The anatomy and physiology of the urinary bladder will be reviewed briefly, as will the various types of bladder cancer and the disease's common symptoms. Additionally, various radiologic technologies used in the detection and diagnosis of bladder cancer will be discussed, as will treatment options for and prognosis of the disease.

Bladder Cancer Epidemiology

Sex Differences

Bladder cancer is the fourth most common malignancy in men after cancers of the prostate, lung and colon (see Table 1). (1) Men account for approximately three-fourths of bladder cancer patients. Differences in bladder cancer incidence based on the patient's sex are significant. Recent data from the Surveillance, Epidemiology, and End Results (SEER) Program of the NCI indicate annual age-adjusted cancer incidence rates of 37.5 for men and 9.6 for women per 100 000 population) Thus, men are 4 times more likely to develop bladder cancer than women. Similarly, a man's lifetime risk for bladder cancer is 1 in 30 compared with 1 in 90 for women.

Racial and Ethnic Differences

The incidence of bladder cancer varies by race and ethnicity, as demonstrated by Figure 1. Overall, whites are diagnosed with bladder cancer nearly twice as often as African Americans, and Hispanic patients have an even lower rate of incidence. However, African Americans typically have more advanced disease at the time of diagnosis, despite lower rates of bladder cancer incidence. (3) Advanced disease at diagnosis contributes to higher mortality rates and might reflect barriers to diagnosis, such as lack of health insurance or a lack of physician recommendation for screening. (1)

[FIGURE 1 OMITTED]

Mortality

The ACS estimated that nearly 14 000 people in the United States died from bladder cancer in 2007. Of these deaths, approximately 10 000 were men and 4000 were women. However, overall mortality from bladder cancer has decreased by approximately 33% since the 1950s. (2) Additionally, bladder cancer mortality differs according to race and ethnicity (see Figure 2). Among both whites and African Americans, bladder cancer mortality is decreasing in spite of the rising incidence. (1) Bladder cancer mortality rates for other racial and ethnic minorities have fluctuated in the United States over the past 2 decades.

Anatomy and Physiology

The urinary bladder is a flexible, muscular bag that collects urine from the kidneys via the ureters for storage and eventual elimination. The average adult bladder can hold approximately 50 to 500 mLs (approximately 2 cups) of urine. Urine is eliminated via the urethra. In women the urethra is a short tube that terminates in front of the vagina. The male urethra is longer and passes through the prostate gland and the penis, terminating at the tip of the penis.

The urinary bladder wall is composed of several layers of tissue, as illustrated in Figure 3. The innermost layer of tissue, the urothelium, is composed of urothelial (or transitional) cells and is the surface that comes into direct contact with the urine in the urinary bladder. These cells are the same type as those that line the kidney collecting system, ureters and urethra. Under the urothelium is the lamina propria (or submucosa), which is a thin area of highly vascularized connective tissue. Under the lamina propria is a thicker layer of smooth muscle tissue known as the muscularis propria. The detrusor muscle is the smooth muscle layer of the urinary bladder wall that contracts upon parasympathetic nervous system stimulation. The contraction of the detrusor muscle causes the bladder to expel urine via the urethra. On the outside of these muscular layers of the bladder is a region of fatty connective tissue called the adventitia.

The urinary bladder is supplied with oxygenated blood by the superior, middle and inferior vesicle arteries arising from the internal iliac artery. The bladder also receives blood from smaller arteries arising from the uterine, vaginal (in women), obturator and inferior gluteal arteries. Lymphatic drainage is supplied by the interstitial vesical lymphatics, which ultimately drain into the external iliac, internal iliac and common iliac lymph node chains.

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

Types of Bladder Cancer

Bladder cancer is divided into the following 2 broad categories:

* Epithelial neoplasms and carcinomas.

* Nonepithelial neoplasms. (4)

Table 2 lists the common cell types found within these 2 broad categories. Urothelial, or transitional cell, carcinoma accounts for about 90% of all bladder malignancies. Squamous cell carcinoma and adenocarcinomas account for approximately 4% to 5% and 1% to 2% of all bladder cancers, respectively. Nonepithelial bladder cancers account for less than 5% of bladder neoplasms. (4,5)

Nearly all squamous cell carcinomas and adenocarcinomas are invasive. (5) In addition, squamous cell carcinoma of the bladder is unusual because, unlike other bladder cancers, the incidence in women is actually twice that of men.

The type of malignancy is important in bladder cancer because different cell types have different rates of growth and respond differently to therapeutic interventions. For example, nonurothelial (ie, squamous cell, adenocarcinoma and nonepithelial types) bladder cancers grow more aggressively and are less responsive to nonsurgical treatments than urothelial carcinoma. (6)

Symptoms

The vast majority of patients with bladder cancer, about 80% to 90%, exhibit hematuria (either macro- or microscopic). Approximately 13% to 35% of patients with macroscopic hematuria have bladder cancer. (7-10) However, the hematuria may be intermittent in nature. Thus, the absence of red blood cells in a urinalysis does not exclude the diagnosis of bladder cancer. Urinary frequency and urinary urgency are additional symptoms. Less common symptoms of bladder cancer include flank pain (due to urinary obstruction) and pelvic pain (due to localized tumor invasion). (2)

Risk Factors

Age, sex, race and ethnicity can place an individual at risk for developing bladder cancer. Those most at risk are older white men. According to the ACS, older white men are at much higher risk than others, but the most significant risk factor is smoking. (5)

The relationship between smoking and bladder cancer is due to the absorption of carcinogens from tobacco smoke into the blood stream via the lungs. Once in the blood, the carcinogens are filtered through the renal system and, ultimately, concentrate in the urine. Concentration of these chemicals in the urine damages the cells that line the bladder and increases the chance of bladder cancer developing. Among the chemicals implicated in smoking-induced bladder cancer are aminobiphenyl and its metabolites. (11)

Exposure to particular industrial chemicals also increases the risk of developing bladder cancer. The key culprits are aromatic amines, benzidine and benzidine derivatives, all of which are used in the production of dyes. (12) Other industry-related risk factors include gases and soot from the combustion of coal, chlorination byproducts in heated water (13) and some aldehydes used in rubber and textile industries. (14) Thus, the jobs with the highest risks are those in textile, leather, rubber and paint manufacturing and those at dry cleaning and printing companies. Other workers at increased risk of developing bladder cancer due to exposure to various chemicals include machinists, hairdressers, painters and truck drivers (due to the potential exposure to diesel fumes). (15)

Chronic irritation or infection of the urinary bladder also is cited as placing individuals at risk for developing bladder cancer. Chronic infections include frequent urinary infections and schistosomiasis, (5) which is an infection caused by a type of flatworm found in some tropical countries. Other risk factors cited to be associated with increased risk of urinary bladder cancer include kidney and bladder stones, the long-term presence of indwelling urinary catheters and pelvic irradiation. (5)

Screening for Bladder Cancer

Although some risk factors for bladder cancer are modifiable and within the individual's control (eg, smoking), other risk factors cannot be changed (eg, aging, sex). Screening for asymptomatic bladder cancer can help detect the disease early, prevent progression to invasive disease and allow for more effective treatment of noninvasive tumors. (16) However, the ACS has not offered guidelines for bladder cancer screening. (1)

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