Bladder Cancer

Background

• Men and persons > 55 years old are most commonly affected.
• Bladder cancer can be classified into non-muscle invasive and muscle invasive diseases based on the depth of invasion.
• The exact cause is unknown, but it is likely multifactorial and may include a combination of environmental factors, chronic bladder irritation, and genetic factors.
• The most important risk factor is tobacco smoke (active and passive).
• The 5-year relative survival is 70% with localized disease, 35% with regional disease, and 5% with distant stage disease.

Evaluation

• Patients commonly present with macroscopic or microscopic hematuria (painless in > 80% of patients) and symptoms of bladder irritation (especially in invasive or high grade tumors), including symptoms suggestive of reduced bladder capacity such as frequency, urgency, and dysuria.
• To establish the diagnosis:
  • Perform complete history with focus on urinary tract symptoms and hematuria (Strong recommendation), and physical examination (Weak recommendation).
  • Perform voided urine cytology as an adjunct to cystoscopy to detect high-grade tumors (Strong recommendation). Cytology or other noninvasive tests do not replace cystoscopy as the primary diagnostic tool (Strong recommendation).
  • Perform cystoscopy in all patients with symptoms suggestive of bladder cancer (Strong recommendation).
  • Imaging studies prior to transurethral resection of bladder tumor (TURBT) may also include:
    • Renal and bladder imaging in patients with hematuria with computed tomography (CT) urography (or IV urography [IVU] if CT urography is not available) (Weak recommendation), or ultrasound (Weak recommendation). Ultrasound cannot replace CT urography for bladder cancer detection;
    • Abdominal/pelvic CT or magnetic resonance imaging (MRI) (Weak recommendation), especially if cystoscopy suggests solid (sessile) or high-grade tumors, or muscle invasive disease;
    • Evaluation of upper tract collecting system (Weak recommendation) with ≥ 1 of the following imaging modalities: CT urography, magnetic resonance urography (MRU), retrograde ureteropyelography plus renal ultrasound or CT without contrast, or ureteroscopy.
  • Confirm diagnosis with histopathology using transurethral resection of bladder tumor (TURBT) (Strong recommendation).
• Additional workup for staging and evaluation may include blood tests, detailed imaging studies (CT, MRI, ultrasound, chest x-ray, positron emission tomography/CT [PET/CT], bone imaging, and/or ureteroscopy), and/or a second TURBT.

Management

Management of non-muscle invasive bladder cancer

• Initial management:
  • Complete TURBT is recommended for the initial treatment of non-muscle invasive bladder cancer (Strong recommendation).
  • Single-dose immediate intravesical chemotherapy (but not immunotherapy) within 24 hours after initial TURBT:
    • consider for all patients (Weak recommendation)
    • offer to patients with tumors presumed to be at low risk or at intermediate risk with previous low recurrence rate (that is, ≤ 1 recurrence per year) and expected European Organization for Research and Treatment of Cancer (EORTC) recurrence score < 5 (Strong recommendation)
  • Secondary surgical treatment
    • A second TURBT within 6 weeks after initial TURBT is indicated in cases of:
      • incomplete initial TURBT (Strong recommendation)
      • no muscle in the sample from initial TURBT for high-grade disease, except for primary CIS (Strong recommendation)
      • large or multifocal lesions (Weak recommendation)
      • any stage T1 tumor (Strong recommendation)
      • any high-risk tumor, except primary CIS (Strong recommendation)
    • Consider radical cystectomy for select high-risk patients with persistent stage cT1, high-grade disease (Weak recommendation).
• Adjuvant treatment is based on clinical stage and risk group stratification.
• Maintenance therapy depends on the induction therapy given.

Management of nonmetastatic muscle invasive bladder cancer

• For patients with cT2-cT4a disease and negative lymph nodes, treatment options include:
  • Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy (Strong recommendation). Adjuvant treatment following surgery is currently not routinely used in clinical practice due to limited supporting evidence; when used, options are based on pathologic risk, and may include chemotherapy or radiation therapy.
  • Bladder preservation therapy for patients who are medically unfit for surgery or seek an alternative to cystectomy (Weak recommendation). Adjuvant treatment depends on the tumor status at reassessment; options may include radiation therapy, cystectomy, TURBT, or best supportive care.
• For patients with cT2-cT4a, disease and negative lymph nodes who are not eligible for cystectomy, initial treatment options include concurrent chemoradiation, or radiation therapy, or TURBT alone (Weak recommendation). Adjuvant treatment depends on tumor status at reassessment; options may include chemotherapy, chemoradiation therapy, palliative TURBT, or best supportive care.
• For patients with cT2-cT4b disease and cN1-N3 positive lymph nodes on biopsy or computed tomography (CT) or magnetic resonance imaging (MRI), initial treatment options include first-line chemotherapy for locally advanced or metastatic disease, or concurrent chemoradiation (Weak recommendation).
• For patients with cT4b disease and negative lymph nodes on biopsy or CT or MRI, initial treatment options include first-line chemotherapy for locally advanced or metastatic disease, or concurrent chemoradiation (Weak recommendation). Follow-up treatment depends on tumor status at reassessment; options include chemotherapy for locally advanced metastatic disease, chemoradiation therapy, definitive radiation therapy, or cystectomy.

Management of metastatic bladder cancer

• Management of metastatic disease confined to lymph nodes:
  • For patients with stage cT4b disease and positive lymph nodes on biopsy, computed tomography, or magnetic resonance imaging; recommended treatments include chemotherapy or concurrent chemoradiation (Weak recommendation).
  • Follow-up treatment depends on tumor status at reassessment; options include radiation therapy, cystectomy, or management as recurrent or persistent disease.
• Management of disseminated metastatic disease:
  • For patients with disseminated metastatic disease, systemic therapy is recommended ( Strong recommendation).
  • Select appropriate chemotherapy regimen also based on performance status, presence of comorbid conditions such as cardiac disease and renal dysfunction, and tumor stage.
  • Encourage all patients to participate in clinical trials of new agents (Weak recommendation); a list of ongoing clinical trials for metastatic bladder cancer can be found at clinicaltrials.gov.
• Management of recurrent or persistent disease
  • For patients with recurrent or persistent disease, either metastatic or with local recurrence after cystectomy, treat with second-line immunotherapy (Strong recommendation) or other second-line systemic therapy (Weak recommendation), or chemoradiation (if radiation therapy was not given previously), or radiation therapy (Weak recommendation).
  • There are no agreed-upon standard second-line chemotherapy regimens; participation in clinical trials of new agents is encouraged (Weak recommendation), see list of ongoing trials at clinicaltrials.gov.