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Genitourinary Disorders
Genitourinary Cancer
Bladder Cancer
Symptoms and Signs
Diagnosis
Prognosis
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Superficial cancers
Invasive cancers
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Bladder Cancer

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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
    Click for Drug Monograph
    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 Tables).

Table 1

PrintOpen table in new window Open table in new window
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
Click for Drug Monograph
C, may reduce risk of recurrence. DoxorubicinSome Trade Names
ADRIAMYCIN
Click for Drug Monograph
and thiotepaSome Trade Names
No US trade name
Click for Drug Monograph
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
Click for Drug Monograph
, 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

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