252 CHAPTER 6 Urological neoplasia

Bladder cancer: presentation

Symptoms

The most common presenting symptom (85% of cases) is painless total hematuria. This may be initial or terminal if the lesion is at the bladder neck or in the prostatic urethra. 34% of patients >50 years of age and 10% under age 50 with macroscopic hematuria have bladder cancer. History of smoking or occupational exposure should raise suspicion for UC in the setting of hematuria.

Asymptomatic microscopic hematuria is found on routine urine sticktesting. Up to 16% of females and 4% of males have dipstick hematuria: <5% of these patients are <50 years of age, while 7–13% of those >50 years will have a malignancy.

Pain is unusual, even if the patient has obstructed upper tracts, since the obstruction and renal deterioration arise gradually. Pain may be caused by locally advanced (T4 disease).

Filling-type lower urinary tract symptoms, such as urgency or suprapubic pain occur. There is almost always microscopic or macroscopic hematuria. This so-called malignant cystitis is typical in patients with CIS.

Recurrent urinary tract infections and pneumaturia due to malignant colovesical fistula are also found. However, this is less common than benign causes such as diverticular and Crohn disease.

More advanced cases may present with lower limb swelling due to lymphatic/venous obstruction, bone pain, weight loss, anorexia, confusion, and anuria (renal failure due to bilateral ureteral obstruction).

Urachal adenocarcinomas may present with a blood or mucus umbilical discharge or a deep subumbilical mass (rare).

Signs

As most patients have superficial localized disease, signs are generally absent. General examination may reveal pallor, indicating anemia due to chronic renal impairment or blood loss in more advanced disease. Abdominal examination may reveal a suprapubic mass in the case of locally advanced disease.

Digital rectal examination may reveal a mass above or involving the prostate. A pelvic exam in females should also be performed. Although the likelihood of diagnosing bladder cancer in patients <50 years of age is low, all patients with these presenting features should be investigated.

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254 CHAPTER 6 Urological neoplasia

Bladder cancer: diagnosis and staging

After a urinary tract infection has been excluded or treated, all patients with microscopic or macroscopic hematuria require investigation of their upper tracts, bladder, and urethra. Usually, renal imaging and flexible cystoscopy with local anesthetic are first-line investigations.

CT urography (CTU) before and after IV contrast is becoming the firstline radiological investigation of hematuria. It is faster and more sensitive than ultrasound or IVP in the detection of renal (parenchymal and urothelial) and ureteral tumors.

CTU also detects some bladder tumors, but may overcall bladder wall hypertrophy as tumor and will miss flat CIS and urethral pathology. CTU cannot replace cystoscopy. If there is hydronephrosis in association with a bladder tumor, it is likely that the tumor is causing the obstruction to the distal ureter caused by muscle-invasive disease.

False-negative cytology is frequent (40–70%) in patients with papillary UC. Overall, routine urine cytology has 50% sensitivity but a high 96% specificity and is most reliable with high-grade UC and CIS. False-positive cytology can occur from infection, inflammation, instrumentation, and chemotherapy.

Fluorescent in situ hybridization (FISH) (sensitivity 77%, specificity 98%) and other tests such as NMP-22 (sensitivity 56%, specificity 85%) may be helpful in the evaluation.

If all investigations are normal, consideration should be given to “medical” causes of hematuria, such as glomerulonephritis or IGA nephropathy. In patients with persisting microscopic hematuria, especially those with associated proteinuria or hypertension, nephrology consultation should be considered.

Transurethral resection of bladder tumor (TURBT)

TURBT usually provides definitive histological diagnosis (see p. 248). This is usually undertaken under general or spinal anesthesia. Bimanual examination is mandatory before and after bladder tumor resection in order to assess size, position, and mobility.

The pathologist should report on the tumor type, grade, and stage. In particular, the presence or absence of muscularis propria should be noted, since its absence will preclude reliable T staging. Suspicious areas are biopsied separately and consideration given to random biopsies to evaluate for CIS.

The prostatic urethra is biopsied if radical reconstructive surgery such as orthotopic neobladder is under consideration. Care should be taken in resecting tumors at the dome, since intraperitoneal bladder perforation may occur, especially in women with thin-walled bladders.

Mitomycin C, given as a single dose within 24 hours of TURBT (40 mg in 40 mL of saline or sterile water), can reduce tumor recurrence but is contraindicated with bladder perforation.

BLADDER CANCER: DIAGNOSIS AND STAGING 255

Staging investigations

These are usually reserved for patients with biopsy-proven muscle-inva- sive bladder cancer unless clinically indicated, since superficial UC and CIS disease are rarely associated with metastases.

•Pelvic CT or MRI may demonstrate extravesical tumor extension or pelvic lymphadenopathy, reported if >5–8 mm in maximal diameter.

•Chest X-ray

•Isotope bone scan (positive in 5–15% of patients with muscle-invasive UC) is obtained in cases being considered for radical treatment.

•Staging lymphadenectomy (open or laparoscopic) may be indicated in the presence of CT-detected pelvic lymphadenopathy if radical treatment is under consideration. However, this is most often performed at the time of radical cystectomy.

256 CHAPTER 6 Urological neoplasia

Management of superficial UC: transurethral resection of bladder tumor (TURBT)

The diagnostic role of TURBT is discussed on p. 254. Therapeutically, a visually complete tumor resection is adequate treatment for 70% of newly presenting patients with Ta/T1 superficial disease. The remaining 30% of patients experience early recurrence, 15% with upstaging. Because of this, it is proposed that all new patients receive adjuvant treatment (see below).

Complications are uncommon and include bleeding, sepsis, bladder perforation, incomplete resection, and urethral stricture. Alternatively, transurethral laser ablation is less likely to cause bleeding, but histological sampling would be inadequate.

Follow-up after TURBT

Most urologists perform review cystoscopy at 3 months. If this demonstrates recurrence, 70% of cases will further recur. If no recurrence is evident, only 20% will further recur. If the bladder is clear at follow-up, further cystoscopies are performed at 6 months and thereafter annually until the patient is no longer fit to undergo treatment.

There is no accepted protocol for upper tract surveillance in patients with a history of bladder UC, although some urologists recommend IVP every 2 years.

Transurethral fulguration (electrosurgical or laser)

This procedure is accepted more quickly and is less morbid for ablating very small, superficial papillary recurrences.

Patients with G3T1 UC and CIS are at significantly higher risk of recurrence and 40% are upstaged. Also, some patients experience persistent symptomatic multifocal G1/2, Ta/1 recurrent UC, which requires frequent follow-up procedures. In these circumstances, adjuvant treatment is indicated (see p. 258).

Patients with high-grade (G3) disease whose biopsy material does not contain muscularis propria should be re-resected early (within a few weeks) since the possibility of muscle invasion has not been excluded. Table 6.9 summarizes the management of bladder cancer, stage by stage.

MANAGEMENT OF SUPERFICIAL UC 259

BCG infection (BCGosis), especially if BCG is administered in a setting of recent surgery or traumatic catheterization, can be seen in a small percentage of patients. They develop a high, persistent fever, requiring antituberculous therapy for up to 6 months with isoniazid and pyridoxine, or standard triple therapy (rifampicin, isoniazid, and ethambutol) in critically ill patients. Granulomatous prostatitis and epididymo-orchitis are rare complications.

Contraindications to intravesical BCG

•Immunosuppressed patients

•Pregnant or lactating women

•Patients with hematological malignancy

•After a traumatic catheterization

•Active UTI

Cystoscopy done too early after BCG can produce alarming-looking effects because of the generalized inflammatory response. Follow-up cystoscopy and biopsy 3 months after BCG may still reveal chronic granulomatous inflammation.

Maintenance BCG (e.g., treatment every 3 months and then every 6 months for 3 years after the initial 6-week course or monthly regimen) demonstrated a benefit for superficial UC, excluding CIS, compared with a single 6-week course.

Maintenance may be associated with a higher risk of side effects.

Recurrent G3T1 UC or CIS

A second course of BCG could be offered; 50% of patients will respond. Otherwise, proceed without delay to radical cystectomy. The latter has a cure rate of 90%.