In the United States in 2016, it is estimated that there will be 76,960 new diagnoses of bladder cancer, with approximately 16,390 deaths.
Urothelial cancers encompass carcinomas of the bladder, ureters, and renal pelvis, which 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 point 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.
Urothelial cancers occur more commonly in men than in women (3:1), with a peak incidence in the seventh decade of life.
Cancers of the urothelial tract are also more common in whites than in blacks (2:1).
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.
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
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 to toxins 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.
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.
There are reports of families (eg, those with Lynch syndrome) with a higher risk of urothelial carcinoma of the urothelium, but the genetic basis for this familial clustering remains undefined.
Blood in the urine is the most common symptom in patients presenting with urothelial tract cancer. It is most often painless, unless there is obstruction due to a clot or tumor and/or deeper levels of tumor invasion have already occurred.
Urinary voiding symptoms
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.
Bladder irritation without hematuria
Vesical irritation without hematuria can be seen, especially in patients with carcinoma in situ of the urinary bladder.
Symptoms of advanced disease
Constitutional symptoms include night sweats, fever, weight loss, and anorexia. Pain can also be a symptom of more advanced disease, as is edema of the lower extremities secondary to lymphatic or venous obstruction.
The initial evaluation of a patient in whom urothelial cancer is suspected consists of excretory urography (computed tomography [CT], magnetic resonance imaging [MRI], or intravenous pyelogram) followed by cystoscopy. Retrograde pyelography can better define the exact location of upper tract lesions. Definitive assessment of upper tract tumors by ureteroscopic examination and biopsy can be accomplished using either 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 compared with 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 select mucosal sites to detect possible concomitant carcinoma in situ. Biopsies of the primary lesion must include the muscularis propia to determine whether there is invasion of the muscle wall by the overlying carcinoma. A repeat biopsy must be performed if no muscle was identified in the original specimen, since significant upstaging occurs with the deeper biopsies.
For urothelial cancers of the upper urinary tract or muscle-invasive bladder cancers, a CT or MRI scan of the abdomen/pelvis is performed to detect local extension of the cancer, involvement of the abdominal/pelvic lymph nodes, or systemic metastases. CT or MRI usually consists of an abdominal/pelvic CT scan with contrast (usually with delayed images, to assess the entire urinary tract).
For patients with bone pain or an elevated alkaline phosphatase level, a radioisotope bone scan is performed.
Chest x-ray film
A chest x-ray film completes the staging evaluation. Any suspicious findings in a chest x-ray film must be followed by a CT scan of the chest.
Transitional cell carcinomas (urothelial carcinomas)
These constitute 90% to 95% of urothelial tract cancers. In approximately 30% of newly diagnosed urothelial bladder tumors, 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 more advanced disease stages.
When carcinoma in situ is associated with superficial tumors, rates of recurrence and disease progression (development of muscle invasion) are higher (50% to 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 go on to develop muscle-invasive bladder cancers.
Squamous cell cancers
These malignancies account for 3% to 7% of urothelial carcinomas and are more common in the renal pelvis and ureters.
These tumors 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.
Urothelial tract cancers are staged according to the American Joint Committee on Cancer 7th edition TNM classification system (Table 1). Superficial bladder cancer includes papillary tumors that involve only the mucosa (Ta) or submucosa (T1) and flat carcinoma in situ (Tis). The natural history of superficial bladder cancer is unpredictable, and recurrences are common. Most tumors recur within 6 to 12 months and are of the same stage and grade, but 10% to 15% of patients with superficial cancer will develop invasive or metastatic disease.
For carcinomas confined to the bladder, ureters, or renal pelvis, the most important prognostic factors are T stage and differentiation pattern. The impact of associated carcinoma in situ on Ta and T1 lesions was discussed previously (see section on “Pathology”). Less differentiated Ta–T1 lesions also are associated with higher recurrence and disease progression rates. Patients with well-differentiated Ta lesions without carcinoma in situ have a 95% survival rate, whereas those with high-grade T1 lesions have a 10-year survival rate of 50%. The presence of lymphovascular invasion or micropapillary features within the surgical specimen appears to be independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with node-negative bladder cancer at the time of cystectomy. As such, the presence of lymphovascular invasion and micropapillary features should be included in the pathologic assessment of bladder cancer.
Muscle-invasive carcinoma carries a 5-year disease-specific survival rate of 40% to 65%. When regional lymph nodes are involved, the 5-year survival rate is 0% to 30%. For patients with unresectable or metastatic bladder cancer, Karnofsky performance status of less than 80% and visceral disease (lung, liver, or bone) have also been shown to predict survival.