UROTHELIAL CANCER

In the year 2008, an estimated 68,810 new cases of bladder cancer will be diagnosed in the United States, and approximately 14,100 patients will die of this disease.

Urothelial cancers encompass carcinomas of the bladder, ureters, and renal pelvis; these cancers occur at a ratio of 50:3:1, respectively. Cancer of the urothelium is a multifocal process. Patients with cancer of the upper urinary tract have a 30% to 50% chance of developing cancer of the bladder at some time in their lives. On the other hand, patients with bladder cancer have a 2% to 3% chance of developing cancer of the upper urinary tract. The incidence of renal pelvis tumors is decreasing.

Epidemiology

Gender Urothelial cancers occur more commonly in men than in women (3:1) and have a peak incidence in the seventh decade of life.

Race Cancers of the urothelial tract are also more common in whites than in blacks (2:1).

Etiology and risk factors

Cigarette smoking The major cause of urothelial cancer is cigarette smoking. A strong correlation exists between the duration and amount of cigarette smoking and cancers at all levels of the urothelial tract. This association holds for both transitional cell and squamous cell carcinomas.

Analgesic abuse Abuse of compound analgesics, especially those containing phenacetin, has been associated with an increased risk of cancers of the urothelial tract. This risk appears to be greatest for the renal pelvis, and cancer at this site is usually preceded by renal papillary necrosis. The risk associated with analgesic abuse is seen after the consumption of excessive amounts (5 kg).

Chronic urinary tract inflammation also has been associated with urothelial cancers. Upper urinary tract stones are associated with renal pelvis cancers. Chronic bladder infections can predispose patients to cancer of the bladder, usually squamous cell cancer.

Occupational exposure has been associated with an increased risk of urothelial cancers. Workers exposed to arylamines in the organic chemical, rubber, and paint and dye industries have an increased risk of urothelial cancer similar to that originally reported for aniline dye workers.

Balkan nephropathy An increased risk of cancer of the renal pelvis and ureters occurs in patients with Balkan nephropathy. This disorder is a familial nephropathy of unknown cause that results in progressive inflammation of the renal parenchyma, leading to renal failure and multifocal, superficial, low-grade cancers of the renal pelvis and ureters.

Genetic factors There are reports of families with a higher risk of transitional cell cancers of the urothelium, but the genetic basis for this familial clustering remains undefined.

Signs and symptoms

Hematuria is the most common symptom in patients presenting with urothelial tract cancer. It is most often painless, unless obstruction due to a clot or tumor and/or deeper levels of tumor invasion have already occurred.

Urinary voiding symptoms of urgency, frequency, and/or dysuria are also seen in patients with cancers of the bladder or ureters but are uncommon in patients with cancers of the renal pelvis.

Vesical irritation without hematuria can be seen, especially in patients with carcinoma in situ of the urinary bladder.

Symptoms of advanced disease Pain is usually a symptom of more advanced disease, as is edema of the lower extremities secondary to lymphatic obstruction.

Diagnosis

Initial work-up The initial evaluation of a patient suspected of having urothelial cancer consists of excretory urography, followed by cystoscopy. In patients with upper tract lesions, retrograde pyelography can better define the exact location of lesions. Definitive urethroscopic examination and biopsy can be accomplished utilizing rigid or flexible instrumentation.

At the time of cystoscopy, urine is obtained from both ureters for cytology, and brush biopsy is obtained from suspicious lesions of the ureter. Brush biopsies significantly increase the diagnostic yield over urine cytology alone. Also, at the time of cystoscopy, a bimanual examination is performed to determine whether a palpable mass is present and whether the bladder is mobile or fixed.

Evaluation of a primary bladder tumor In addition to biopsy of suspicious lesions, evaluation of a bladder primary tumor includes biopsy of selected mucosal sites to detect possible concomitant carcinoma in situ. Biopsies of the primary lesion must include bladder wall muscle to determine whether there is invasion of muscle by the overlying carcinoma.

CT For urothelial cancers of the upper tract or muscle invasive bladder cancers, a CT scan of the abdomen/pelvis is performed to detect local extension of the cancer and involvement of the abdominal lymph nodes.

Bone scan For patients with bone pain or an elevated alkaline phosphatase level, a radioisotope bone scan is performed.

A chest x-ray completes the staging evaluation.

Pathology

Transitional cell carcinomas constitute 90% to 95% of urothelial tract cancers.

Squamous cell cancers account for 3% to 7% of urothelial carcinomas and are more common in the renal pelvis and ureters.

Adenocarcinomas account for a small percentage (< 3%) of bladder malignancies and are predominantly located in the trigone region. Adenocarcinomas of the bladder that arise from the dome are thought to be urachal in origin.

Carcinoma in situ In approximately 30% of newly diagnosed bladder cancers, there are multiple sites of bladder involvement, most commonly with carcinoma in situ. Although carcinoma in situ can occur without macroscopic cancer, it most commonly accompanies higher disease stages.

When carcinoma in situ is associated with superficial tumors, rates of recurrence and disease progression (development of muscle invasion) are higher (50%–80%) than when no such association is present (10%). Carcinoma in situ involving the bladder diffusely without an associated superficial tumor is also considered an aggressive disease. Most patients with this type of cancer will develop invasive cancers of the bladder.