What are the treatment options for bladder cancer?

Treatment Options for Bladder Cancer

The treatment of bladder cancer should be based on tumor stage, grade, and depth of invasion, with options ranging from transurethral resection with intravesical therapy for non-muscle invasive disease to radical cystectomy with neoadjuvant chemotherapy for muscle-invasive tumors. 1

Non-Muscle Invasive Bladder Cancer (NMIBC)

Initial Management

• Complete transurethral resection of bladder tumor (TURBT) is the primary treatment for any initial bladder tumor 1
• Multiple selective and/or random biopsies should be performed for suspected or known carcinoma in situ 1
• Repeat TURBT is necessary if:
  • No muscle is present in the specimen for high-grade disease
  • Any T1 lesion is present
  • First resection does not allow adequate staging 1

Adjuvant Treatment Based on Risk Stratification

• Low-risk tumors (Ta, low-grade, <3 cm):

  • Observation or single-dose intravesical chemotherapy within 24 hours 1
  • Cystoscopy follow-up at 3 months, with increasing intervals as appropriate 1

• Intermediate-risk tumors (low-grade recurrent, multiple or >3 cm):

  • Multiple chemotherapeutic instillations 1
  • Intravesical chemotherapy with mitomycin 1

• High-risk tumors (T1, high-grade, or carcinoma in situ):

  • BCG intravesical therapy is preferred (category 1) 1
  • BCG has been shown to prevent recurrences and reduce mortality by 23% 1
  • If BCG fails, cystectomy should be considered due to high risk of progression 1

Muscle-Invasive Bladder Cancer (MIBC)

Primary Treatment Options

• Radical cystectomy with extended lymphadenectomy is the standard treatment for MIBC 1

  • Should include bilateral pelvic lymphadenectomy (common, internal iliac, external iliac, and obturator nodes) 1
  • Strongly consider neoadjuvant cisplatin-based combination chemotherapy before cystectomy (category 1) 1

• Segmental (partial) cystectomy may be considered for:

  • Solitary lesion in location amenable to segmental resection with adequate margins
  • No carcinoma in situ present 1
  • Bilateral pelvic lymphadenectomy should still be performed 1

• Bladder preservation approaches:

  • Trimodality therapy: Maximal TURBT + concurrent chemotherapy + radiation therapy 1
  • Ideal candidates: Initial T2 tumor <5 cm, no CIS, pT0 after second TURBT, no hydronephrosis, good performance status 1
  • Cystoscopy with bladder biopsy is mandatory for response evaluation 1
  • If persistent/recurrent disease is observed, prompt salvage cystectomy is recommended 1

Special Considerations for MIBC

• Extended lymphadenectomy has been shown to be beneficial and may be curative in patients with limited nodal disease 1
• Adjuvant chemotherapy is not recommended for routine use but may be considered in node-positive patients 1

Advanced/Metastatic Bladder Cancer (Stage IV)

• First-line therapy:

  • Platinum-based combination chemotherapy (MVAC or gemcitabine-cisplatin) prolongs survival (category 1) 1
  • For cisplatin-ineligible patients: carboplatin-based regimen or single-agent taxane or gemcitabine 1

• Second-line therapy:

  • Immunotherapy with checkpoint inhibitors (e.g., pembrolizumab) for patients with locally advanced or metastatic disease 2
  • Pembrolizumab is indicated for patients with disease progression during/following platinum-containing chemotherapy 2

Non-Urothelial Bladder Cancer

• Treatment varies based on histologic subtype:
  • Mixed histology: Treated similarly to pure urothelial carcinoma but with consideration of worse prognosis 1
  • Pure squamous: Cystectomy, RT, or agents like 5-FU, taxanes, and methotrexate 1
  • Adenocarcinoma: Radical or segmental cystectomy; conventional chemotherapy less effective 1
  • Small-cell component: Neoadjuvant chemotherapy using small-cell regimens followed by local treatment 1
  • Urachal carcinoma: Complete urachal resection including the umbilicus 1
  • Primary bladder sarcoma: Treatment as per soft tissue sarcoma guidelines 1

Follow-Up After Treatment

• After radical cystectomy:

  • Urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated
  • Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk
  • Urethral wash cytology every 6-12 months, particularly if Tis was found 1

• After bladder preservation:

  • Cystoscopy and urinary cytology every 3 months during first 2 years, then every 6 months 1
  • Consider imaging of upper tract every 1-2 years for high-grade tumors 1

Common Pitfalls to Avoid

• Failure to perform adequate initial TURBT with muscle in the specimen can lead to understaging 1
• Underutilization of BCG therapy in appropriate high-risk NMIBC patients 1
• Delaying cystectomy in patients with BCG-refractory high-risk NMIBC 1
• Omitting neoadjuvant chemotherapy before radical cystectomy for MIBC, which has demonstrated survival benefit 1
• Inappropriate patient selection for bladder preservation approaches, which require strict selection criteria 1