• Clinical science

Urothelial cancer

Summary

Carcinoma of the epithelial lining of the urinary tract is known as urothelial cancer and may involve the bladder (most common), renal pelvis, ureters, and urethra (rare). Most urothelial cancers occur in males > 65 years, esp. those who have a history of smoking or exposure to carcinogens. Patients often present with painless gross hematuria or irritative voiding symptoms, although some cases are incidentally detected (microscopic hematuria on urinalysis). Urine cytology, cystoscopy, and CT urography are indicated in all patients with gross hematuria or in patients > 35 years of age with microhematuria and risk factors for urothelial cancer. Non-muscle, invasive bladder tumors are treated with transurethral resection of the tumor and intravesical instillation of BCG or chemotherapeutic agents. Muscle invasive bladder tumors are treated with radical cystectomy and chemotherapy or chemoradiation. Since cancers of the renal pelvis are often multifocal and have a high risk of recurrence, treatment requires nephroureterectomy. Metastatic urothelial cancer is treated with palliative chemotherapy and/or chemoradiation. Close follow-up post-treatment is necessary to identify and treat recurrent disease.

Epidemiology

References:[1][2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

Risk factors for urothelial cancer

References:[1][2][3][4][6][7][8][9]

Clinical features

Location Symptoms Features of advanced/metastatic disease
Bladder carcinoma
  • Painless gross hematuria throughout micturition (most common)
  • Irritative voiding symptoms (dysuria, urinary frequency, urgency)
  • Bladder outlet obstruction (rare)
  • Suprapubic/rectal/perineal pain
  • Palpable suprapubic mass (advanced cases)

Carcinoma of the renal pelvis

Ureteral carcinoma

  • Painless gross hematuria throughout micturition
  • Flank pain
Urethral carcinoma
  • Painless gross hematuria at the beginning of micturition
  • Bladder outlet obstruction
  • Irritative voiding symptoms (common, esp. in women)
  • Palpable inguinal lymphadenopathy
  • Urethral discharge
  • A mass may be palpable along the urethra (bimanual examination in women).

References:[10][11][3][12][4]

Diagnostics

Laboratory investigations

Imaging and biopsy

CT urography and cystoscopy are indicated in all patients with gross hematuria and in patients > 35 years with asymptomatic microhematuria; . Physicians may consider cystoscopy and/or CT urography in patients < 35 years with asymptomatic hematuria who also have risk factors for CIS. These procedures enable diagnostic evaluation of the entire urinary tract, as well as follow-up.

  • CT urography: Imaging modality of choice to examine the entire urinary tract.
    • Non-enhanced phase: areas of mural thickening (bladder, pelvis, ureter) with soft tissue density may be seen
    • Excretory phase:
      • Urothelial tumors are seen as filling defects
      • Can detect hydronephrosis
  • Cystoscopy and biopsy: direct visualization of urethral and bladder mucosa with possible simultaneous biopsies or therapeutic resections
    • CIS: focal or diffuse erythematous, flat, velvety lesion(s) in the bladder mucosa
    • Low-grade tumors: pedunculated with a papillary surface and non-invasive
    • High-grade tumors: sessile and nodular/solid and invasive (invading lamina propria or deeper tissues)
  • Ultrasound (kidney, ureter, bladder): if CT is contraindicated (e.g., pregnant women)
  • Retrograde urethrogram: detects location and extent of invasion of urethral tumors
  • Flexible ureteroscopy: evaluation of ureteral lesions

Since urothelial tumors can be multifocal, the entire urinary tract must be evaluated!

Staging

References:[10][13][14][15][16][17][11][3][12][4]

Pathology

Differential diagnoses

Other causes of hematuria and flank pain

References:[13][18]

The differential diagnoses listed here are not exhaustive.

Treatment

Treatment of urothelial cancers involves surgical resection with neoadjuvant chemotherapy and/or radiation; . All cases of metastatic disease are managed with palliative systemic chemotherapy and palliative surgery, if needed (e.g., removal of urethral obstructions).

Bladder cancer

Carcinoma of the renal pelvis and ureters

  • Nonmetastatic disease: nephroureterectomy with excision of bladder mucosa adjacent to the ureteric orifice; indicated in all patients
  • High-grade, lymph node positive patients: : additional regional lymphadenectomy and adjuvant chemotherapy (e.g., gemcitabine and cisplatin for 4 cycles)

Urethral carcinoma

  • Non-invasive tumors: : transurethral resection of tumor with intraurethral instillation of chemotherapy/BCG
  • Invasive tumors: : resection, followed by chemotherapy or chemoradiotherapy

Follow-up

  • Follow-up procedures depend on the grade and stage of the tumor.
  • In general, follow-up includes:

References:[3][12][19][20][21][22][23]

Prognosis

  • 5-year survival of bladder, ureteral, and pelvic cancer is 90–95% for noninvasive disease and ∼ 12% for metastatic disease.
  • Prognosis of urethral cancer is poorer (5-year survival of ∼ 45%).

References:[3][12][24]

Prevention

References:[21]