Bladder cancer is usually transitional cell carcinoma. Symptoms include hematuria; later, urinary obstruction can cause pain. Diagnosis is by cystoscopy and biopsy. Treatment is with fulguration, intravesical instillations, surgery, chemotherapy, or a combination.

In the US, > 70,000 new cases of bladder cancer and about 14,700 deaths occur each year. Bladder cancer is the 4th most common cancer among men and is less common among women; male:female incidence is about 3:1. Bladder cancer is more common among whites than blacks, and incidence increases with age.

Risk factors include the following:

• Smoking (the most common risk factor, causing ≥ 50% of new cases)
• Excess phenacetin use (analgesic abuse)
• Long-term cyclophosphamideSome Trade Names
  CYTOXAN
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  use
• Chronic irritation (eg, in schistosomiasis or by bladder calculi)
• Exposure to hydrocarbons, tryptophan metabolites, or industrial chemicals, notably aromatic amines (aniline dyes, such as naphthylamine used in the dye industry) and chemicals used in the rubber, electric, cable, paint, and textile industries

Types of bladder cancer include

• Transitional cell carcinomas, which account for > 90% of bladder cancers. Most are papillary carcinomas, which tend to be superficial and well-differentiated and to grow outward; sessile tumors are more insidious, tending to invade early and metastasize.
• Squamous cell carcinomas, which are less common and usually occur in patients with parasitic bladder infestation or chronic mucosal irritation.
• Adenocarcinomas, which may occur as primary tumors or may reflect metastasis from intestinal carcinoma. Metastasis should be ruled out.

In > 40% of patients, tumors recur at the same or another site in the bladder, particularly if tumors are large or poorly differentiated or if several tumors are present. Bladder cancer tends to metastasize to the lymph nodes, lungs, liver, and bone. Expression of tumor gene p53 may be associated with progression.

In the bladder, carcinoma in situ is high grade but noninvasive and usually multifocal; it tends to recur.

Symptoms and Signs

Most patients present with unexplained hematuria (gross or microscopic). Some patients present with anemia, and hematuria is detected during evaluation. Irritative voiding symptoms (dysuria, burning, frequency) and pyuria are also common at presentation. Pelvic pain occurs with advanced cancer, when a pelvic mass may be palpable.

Diagnosis

• Cystoscopy with biopsy

Bladder cancer is suspected clinically. Urine cytology, which may detect malignant cells, may be done. Cystoscopy (see Genitourinary Tests and Procedures: Cystoscopy) and biopsy of abnormal areas are usually also done initially because these tests are needed even if urine cytology is negative. The role for urinary antigen tests is still evolving, particularly for low-grade tumors.

For low-stage (superficial, stage T1) tumors, which comprise 70 to 80% of bladder cancers, cystoscopy with biopsy is sufficient for staging. If a tumor is found to invade muscle (≥ stage T2), abdominal and pelvic CT and chest x-ray are done to determine tumor extent and evaluate for metastases. Patients with invasive tumors undergo bimanual examination (rectal examination in men, rectovaginal examination in women) while under anesthesia for cystoscopy and biopsy. The standard TNM (tumor, node, metastasis) staging system is used (see Table 1: Genitourinary Cancer: Genitourinary Cancer Staging ).

Table 1
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Genitourinary Cancer Staging  AJCC/TNM* Renal Cell Carcinoma Bladder Prostate Urethra Penis Testis Ta Noninvasive papillary Noninvasive papillary, polypoid, or verrucous Noninvasive verrucous T1 ≤ 7 cm in greatest dimension Limited to kidney Invades subepithelial connective tissue Clinically inapparent by palpation or imaging Invades subepithelial connective tissue Invades subepithelial connective tissue Limited to testis and epididymis without vascular or lymphatic invasion May invade tunica albuginea but not tunica vaginalis T1a ≤ 4 cm in greatest dimension Incidentally found in ≤ 5% of resected tissue T1b > 4 cm but ≤ 7 cm in greatest dimension Incidentally found in > 5% of resected tissue T1c Identified by needle biopsy done for elevated prostate-specific antigen level T2 > 7 cm in greatest dimension Limited to kidney Invades muscle Is palpable or reliably visible by imaging Limited to prostate Infiltrates periurethral muscle, corpus spongiosum, or prostate Invades corpus spongiosum or corpus cavernosum Limited to testis and epididymis with vascular or lymphatic invasion May extend through tunica albuginea and involve tunica vaginalis T2a Invades superficial muscle (inner half) Involves ≤ 50% of one lobe T2b Invades deep muscle (outer half) Involves > 50% of one lobe and spares the other lobe T2c Involves both lobes T3 Extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerota's fascia Invades perivesical tissue Extends through the prostatic capsule Infiltrates beyond periurethral tissue (vagina or bladder neck in women; beyond prostatic capsule, corpus cavernosum, or bladder neck in men) Invades urethra or prostate Invades spermatic cord with or without vascular or lymphatic invasion T3a Directly invades adrenal gland or perirenal or renal sinus fat Invades perivesical tissue microscopically Extends through the prostatic capsule unilaterally or bilaterally T3b Grossly extends into the renal vein, its segmental branches, or vena cava below the diaphragm Invades perivesical tissue macroscopically (extravesical mass) Invades seminal vesicles T3c Grossly extends into vena cava above the diaphragm or invades the wall of the vena cava T4 Invades beyond Gerota's fascia Invades adjacent organs Is fixed or invades adjacent structures other than seminal vesicles Invades other adjacent structures Invades scrotum with or without vascular or lymphatic invasion T4a Invades prostate, uterus, or vagina T4b Invades pelvic or abdominal wall *AJCC/TNM staging also includes number of regional lymph nodes involved: NX = not assessable N0 = no evidence of tumor N1–N3, depending on primary location, nodes affected, and size of nodal metastasis and presence of distant metastases: MX = not assessable M0 = none M1= present Further distinctions within a category may be indicated by a lower-case letter. AJCC = American Joint Commission on Cancer; TNM = tumor, node, metastasis. Genitourinary Cancer Staging  AJCC/TNM* Renal Cell Carcinoma Bladder Prostate Urethra Penis Testis Ta Noninvasive papillary Noninvasive papillary, polypoid, or verrucous Noninvasive verrucous T1 ≤ 7 cm in greatest dimension Limited to kidney Invades subepithelial connective tissue Clinically inapparent by palpation or imaging Invades subepithelial connective tissue Invades subepithelial connective tissue Limited to testis and epididymis without vascular or lymphatic invasion May invade tunica albuginea but not tunica vaginalis T1a ≤ 4 cm in greatest dimension Incidentally found in ≤ 5% of resected tissue T1b > 4 cm but ≤ 7 cm in greatest dimension Incidentally found in > 5% of resected tissue T1c Identified by needle biopsy done for elevated prostate-specific antigen level T2 > 7 cm in greatest dimension Limited to kidney Invades muscle Is palpable or reliably visible by imaging Limited to prostate Infiltrates periurethral muscle, corpus spongiosum, or prostate Invades corpus spongiosum or corpus cavernosum Limited to testis and epididymis with vascular or lymphatic invasion May extend through tunica albuginea and involve tunica vaginalis T2a Invades superficial muscle (inner half) Involves ≤ 50% of one lobe T2b Invades deep muscle (outer half) Involves > 50% of one lobe and spares the other lobe T2c Involves both lobes T3 Extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerota's fascia Invades perivesical tissue Extends through the prostatic capsule Infiltrates beyond periurethral tissue (vagina or bladder neck in women; beyond prostatic capsule, corpus cavernosum, or bladder neck in men) Invades urethra or prostate Invades spermatic cord with or without vascular or lymphatic invasion T3a Directly invades adrenal gland or perirenal or renal sinus fat Invades perivesical tissue microscopically Extends through the prostatic capsule unilaterally or bilaterally T3b Grossly extends into the renal vein, its segmental branches, or vena cava below the diaphragm Invades perivesical tissue macroscopically (extravesical mass) Invades seminal vesicles T3c Grossly extends into vena cava above the diaphragm or invades the wall of the vena cava T4 Invades beyond Gerota's fascia Invades adjacent organs Is fixed or invades adjacent structures other than seminal vesicles Invades other adjacent structures Invades scrotum with or without vascular or lymphatic invasion T4a Invades prostate, uterus, or vagina T4b Invades pelvic or abdominal wall *AJCC/TNM staging also includes number of regional lymph nodes involved: NX = not assessable N0 = no evidence of tumor N1–N3, depending on primary location, nodes affected, and size of nodal metastasis and presence of distant metastases: MX = not assessable M0 = none M1= present Further distinctions within a category may be indicated by a lower-case letter. AJCC = American Joint Commission on Cancer; TNM = tumor, node, metastasis.

Prognosis

Superficial bladder cancer (carcinoma in situ, stage Ta or T1) rarely causes death. For patients with invasion of the bladder musculature, the 5-yr survival rate is about 50%, but adjuvant chemotherapy may improve these results. Generally, prognosis for patients with progressive or recurrent invasive bladder cancer is poor. Prognosis for patients with squamous cell carcinoma or adenocarcinoma of the bladder is also poor, because these cancers are usually highly infiltrative and detected only at an advanced stage.

Treatment

• Transurethral resection and intravesical chemotherapy (for superficial cancers)
• Cystectomy (for invasive cancers)

Superficial cancers: Superficial cancers can be completely removed by transurethral resection or fulguration. Repeated bladder instillations of chemotherapeutic drugs, such as mitomycinSome Trade Names
MUTAMYCIN
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C, may reduce risk of recurrence. DoxorubicinSome Trade Names
ADRIAMYCIN
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and thiotepaSome Trade Names
No US trade name
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are alternatives but rarely used. For carcinoma in situ and other high-grade, superficial, transitional cell carcinomas, immunotherapeutic treatments, such as BCG instillation, alone or in conjunction with interferon alfa-2bSome Trade Names
ROFERON
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, after transurethral resection is generally more effective than chemotherapy instillations.

Invasive cancers: Tumors that penetrate the muscle (ie, ≥ stage T2) usually require radical cystectomy (removal of bladder and adjacent structures) with concomitant urinary diversion; partial cystectomy is possible for < 5% of patients. Cystectomy is being done with increasing frequency after initial chemotherapy in patients with locally advanced disease. Urinary diversion traditionally involves routing urine through an ileal conduit to an abdominal stoma and collecting it in an external drainage bag. Alternatives such as orthotopic neobladder or continent cutaneous diversion are very common and are appropriate for many, if not most, patients. For both procedures, an internal reservoir is constructed from the intestine. For the orthotopic neobladder, the reservoir is connected to the urethra. Patients empty the reservoir by relaxing the pelvic floor muscles and increasing abdominal pressure, so that urine passes through the urethra almost naturally. Most patients maintain urinary control during the day, but some incontinence may occur at night. For continent cutaneous urinary diversion, the reservoir is connected to a continent abdominal stoma. Patients empty the reservoir by self-catheterization at regular intervals throughout the day.

If surgery is contraindicated or refused, radiation therapy alone or with chemotherapy may provide 5-yr survival rates of 20 to 40%. Radiation therapy may cause radiation cystitis or proctitis or bladder contracture.

Patients should be monitored every 3 to 6 mo for progression or recurrence.

Metastatic and recurrent cancers: Metastases require chemotherapy, which is frequently effective but rarely curative unless metastases are confined to lymph nodes. Combination chemotherapy may prolong life in patients with metastatic disease.

Treatment of recurrent cancer depends on clinical stage and site of recurrence and previous treatment. Recurrence after transurethral resection of superficial tumors is usually treated with a 2nd resection or fulguration.

Last full review/revision December 2007 by David A. Swanson, MD

Content last modified February 2012