What are the treatment options for bladder cancer?

Treatment Options for Bladder Cancer

The treatment of bladder cancer depends on the stage of disease, with options ranging from transurethral resection with intravesical therapy for non-muscle invasive disease to radical cystectomy, chemotherapy, and radiation therapy for muscle-invasive and advanced disease 1.

Classification and Staging

Bladder cancer is classified into:

• Non-muscle invasive bladder cancer (NMIBC): Includes Ta (confined to mucosa), T1 (invades lamina propria), and carcinoma in situ (CIS)
• Muscle invasive bladder cancer (MIBC): T2-T4 disease
• Advanced/metastatic disease: Locally advanced (T4b) or metastatic (N1-3, M1)

Treatment by Stage

Non-Muscle Invasive Bladder Cancer (NMIBC)

1. Initial Treatment:

   • Transurethral resection of bladder tumor (TURBT) is the primary treatment 1
   • Early repeat TURBT (within 6 weeks) if:
     • Incomplete initial resection
     • No muscle in specimen for high-grade disease
     • Any T1 lesion
     • Large or multifocal tumors 1

2. Adjuvant Therapy (based on risk stratification):

   • Low-risk: Single immediate postoperative intravesical chemotherapy (mitomycin C) 1
   • Intermediate-risk: Intravesical chemotherapy or BCG 1
   • High-risk: Intravesical BCG therapy 1
   • BCG-unresponsive disease: Consider pembrolizumab or nadofaragene firadenovec for patients ineligible for or refusing cystectomy 1

3. Surveillance:

   • Cystoscopy and cytology every 3 months for 2 years, then every 6 months thereafter 1
   • Upper tract imaging for high-risk patients 1

Muscle Invasive Bladder Cancer (MIBC)

1. Radical Cystectomy:

   • Standard treatment for T2-T4a, N0, M0 disease 1
   • Should include bilateral pelvic lymphadenectomy 1
   • Neoadjuvant cisplatin-based chemotherapy improves survival and is recommended before surgery 1
   • Consider adjuvant chemotherapy for node-positive patients 1

2. Bladder Preservation Approach:

   • Option for patients seeking alternatives to cystectomy or medically unfit for surgery 1
   • Consists of maximal TURBT followed by concurrent chemoradiotherapy 1
   • Best candidates: T2 tumors <5 cm, no CIS, complete TURBT, no hydronephrosis 1
   • Requires close follow-up with cystoscopy and cytology 1

3. Partial Cystectomy:

   • Reserved for solitary lesions in locations amenable to segmental resection 1
   • No carcinoma in situ 1
   • Should include bilateral pelvic lymphadenectomy 1

Advanced/Metastatic Disease

1. First-line Treatment:

   • Cisplatin-eligible patients: Cisplatin-based combination chemotherapy (gemcitabine-cisplatin or MVAC) 1
   • Cisplatin-ineligible, PD-L1 positive: Atezolizumab or pembrolizumab 1
   • Cisplatin-ineligible, PD-L1 negative/unknown: Gemcitabine-carboplatin 1

2. Maintenance Therapy:

   • Avelumab for patients without disease progression after first-line chemotherapy 1

3. Second-line Treatment:

   • Pembrolizumab 1
   • Enfortumab vedotin 1
   • Erdafitinib (for FGFR alterations) 1

4. Palliative Treatment:

   • Radiation therapy for symptom control (bleeding, pain) 1

Special Considerations

Non-Urothelial Histologies

Treatment should be adapted based on histologic subtype 1:

• Mixed histology: Generally treated like urothelial carcinoma but with worse prognosis
• Pure squamous: Cystectomy, RT, or agents used for squamous cell carcinoma
• Adenocarcinoma: Radical or partial cystectomy; conventional chemotherapy less effective
• Small-cell component: Neoadjuvant chemotherapy using small-cell regimens followed by local treatment
• Urachal carcinoma: Complete urachal resection with umbilicus
• Primary bladder sarcoma: Treat according to soft tissue sarcoma guidelines

Elderly Patients

• Treatment should consider age, performance status, comorbidities, and quality of life 2
• Single-agent regimens preferred over combination therapy 2
• Carboplatin-based regimens may be considered if renal function permits 2
• Cisplatin-based combination chemotherapy should be avoided due to excessive toxicity 2
• Palliative radiation (30-45 Gy) effective for local symptom control 2

Common Pitfalls and Caveats

1. Delayed cystectomy: Cystectomy should be performed within 3 months of diagnosis if no therapy is given 1

2. Inadequate TURBT: Incomplete resection leads to understaging and suboptimal outcomes; ensure muscle is present in the specimen for proper staging 1

3. Overlooking variant histologies: These often have more aggressive behavior and may require different treatment approaches 1

4. Neglecting upper tract monitoring: Regular upper tract imaging is necessary, especially for high-risk NMIBC patients 1, 3

5. Inappropriate patient selection for bladder preservation: Best results are in patients with smaller solitary tumors, negative nodes, no CIS, and good bladder function 1