What is the treatment for bladder cancer?

Treatment of Bladder Cancer

Treatment of bladder cancer is determined by whether the disease is non-muscle invasive (NMIBC) or muscle-invasive (MIBC), with complete transurethral resection (TURBT) and intravesical therapy for NMIBC, and radical cystectomy with neoadjuvant cisplatin-based chemotherapy for MIBC. 1

Non-Muscle Invasive Bladder Cancer (NMIBC)

Initial Management

• Complete TURBT is the primary treatment for any initial bladder tumor, ensuring adequate sampling of muscle tissue to confirm invasion depth 2, 1
• A second TURBT is mandatory if no muscle is present in the specimen for high-grade disease, any T1 lesion, or inadequate initial staging 1
• Multiple selective and/or random biopsies should be performed for suspected carcinoma in situ (CIS), including from reddish suspicious areas or prostatic urethra if the tumor is at the trigone/bladder neck 2

Risk-Stratified Treatment

Low-Risk Tumors (initial, low-grade, <3 cm):

• Single-dose intravesical chemotherapy within 24 hours of TURBT 1
• Observation is an alternative option 1
• Cystoscopy follow-up at 3 months, then at increasing intervals 1

Intermediate-Risk Tumors (low-grade recurrent, multiple, or >3 cm):

• Multiple intravesical chemotherapy instillations with mitomycin 2, 1
• This approach has category 1 evidence 1

High-Risk Tumors (high-grade, T1, or CIS):

• BCG intravesical therapy is the standard treatment, which prevents recurrences and reduces mortality by 23% 1
• Both induction and maintenance BCG regimens should be administered 1
• If no response to BCG occurs, radical cystectomy should be performed due to high progression risk 2

Muscle-Invasive Bladder Cancer (MIBC)

Standard Treatment Approach

For Stage II-III Disease (T2-T4a, N0-N1):

• Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with bilateral pelvic lymphadenectomy is the standard of care 2, 1
• The neoadjuvant approach demonstrates a 5% survival benefit at 5 years based on two large randomized trials and meta-analysis 2
• Lymphadenectomy must include at minimum the common iliac, internal iliac, external iliac, and obturator nodes 1

Chemotherapy Regimens

Preferred neoadjuvant regimens (category 1 evidence):

• DDMVAC (dose-dense methotrexate, vinblastine, doxorubicin, cisplatin) with growth factor support for 3-4 cycles 2
• Gemcitabine-cisplatin for 4 cycles 2, 1

Critical timing consideration:

• Cystectomy should be performed within 3 months of diagnosis if no neoadjuvant therapy is given, as delays beyond this negatively impact outcomes 1

Alternative Approaches

Bladder Preservation (Trimodality Therapy):

• May be considered for highly selected patients with initial T2 tumors <5 cm, no CIS, pT0 after second TURBT, no hydronephrosis, and good performance status 2
• Consists of maximal TURBT followed by concurrent chemoradiotherapy 2
• Radiosensitizing regimens include cisplatin/5-FU, cisplatin/paclitaxel, 5-FU/mitomycin C, or cisplatin alone (doublet chemotherapy preferred) 2

Segmental cystectomy:

• Reserved only for solitary lesions in locations amenable to resection with adequate margins and no CIS present 1
• Generally not appropriate for T3 disease 1

Adjuvant Therapy Considerations

• If neoadjuvant chemotherapy was not given, adjuvant chemotherapy may be considered for pathologic high-risk features (≥pT3, pT4, or N+) 2, 1
• However, available trials provide insufficient evidence for routine use of adjuvant chemotherapy in clinical practice 2
• Neoadjuvant chemotherapy is strongly preferred over adjuvant therapy based on superior evidence 1

Advanced/Metastatic Disease (Stage IV)

First-line systemic therapy:

• Platinum-based combination chemotherapy with MVAC or gemcitabine-cisplatin prolongs survival (category 1 evidence) 2
• Cisplatin is FDA-approved as a single agent for transitional cell bladder cancer not amenable to local treatments 3

For cisplatin-ineligible patients:

• Carboplatin-based regimens, single-agent taxane, or gemcitabine may be used for palliation 2

Immunotherapy options:

• Pembrolizumab is FDA-approved for locally advanced or metastatic urothelial carcinoma in patients not eligible for platinum-containing chemotherapy or with disease progression during/following platinum therapy 4
• Pembrolizumab is also approved for BCG-unresponsive, high-risk NMIBC with CIS in patients ineligible for or declining cystectomy 4

Follow-Up Protocols

After radical cystectomy:

• Urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated 1
• Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk 1
• Urethral wash cytology every 6-12 months, particularly if CIS was present in bladder or prostatic urethra 1
• Annual vitamin B12 monitoring if continent diversion was created 1

After bladder preservation:

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

Critical Pitfalls to Avoid

• Inadequate lymphadenectomy compromises both staging and therapeutic outcomes 1
• Delaying cystectomy beyond 3 months from diagnosis worsens prognosis 1
• Failure to perform second TURBT for high-grade or T1 lesions risks understaging 1
• Not obtaining muscle tissue in initial TURBT specimen prevents accurate staging 2
• Positive surgical margins significantly impact survival and must be avoided 1
• Patients with histological variants (e.g., glandular differentiation) require closer follow-up due to more aggressive disease course 1