What is a recommended bladder-preserving protocol for locally advanced carcinoma (ca) of the urinary bladder?

Bladder-Preserving Protocol for Locally Advanced Bladder Cancer

For locally advanced bladder cancer, the recommended bladder-preserving protocol consists of maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy with cisplatin-based chemotherapy and radiation therapy to 64-65 Gy, with mandatory cystoscopic restaging to assess response and determine need for salvage cystectomy. 1

Patient Selection Criteria

Ideal candidates for bladder preservation must meet specific criteria to optimize outcomes:

• Tumor characteristics: T2 disease <5 cm, solitary lesions, no carcinoma in situ (CIS), and no tumor-related hydronephrosis 1
• Surgical factors: Visibly complete TURBT with pT0 status after repeat resection 1
• Patient factors: Good performance status, adequate bladder capacity and function, and no obstructed ureters 1
• Nodal status: Negative lymph nodes (N0) 1

Critical exclusion: Patients with hydronephrosis are poor candidates for bladder-sparing procedures and should proceed to cystectomy 1

Treatment Protocol Algorithm

Phase 1: Maximal TURBT

• Perform aggressive transurethral resection with goal of complete tumor removal 1
• Ensure muscle is present in specimen for adequate staging 2
• Conduct bimanual examination under anesthesia to assess extravesical extension 1
• Perform repeat TURBT within 4 weeks if initial resection incomplete 1

Phase 2: Induction Chemoradiotherapy

Radiation therapy specifications:

• Deliver 45-50.4 Gy to pelvis using 3D conformal or IMRT techniques 1
• Use 1.8 Gy daily fractions 3

Concurrent chemotherapy regimen (choose one):

• Cisplatin alone: 20 mg/m² daily on days 1-5 and 29-33 of radiation 3
• Cisplatin + 5-fluorouracil: Cisplatin 20 mg/m² daily days 1-5 and 29-33, plus 5-FU 600 mg/m² continuous infusion over 120 hours 3
• 5-FU + mitomycin C: Demonstrated improved locoregional control in BC2001 trial 1

The NCCN endorses concurrent cisplatin as the most common chemoradiation method 1

Phase 3: Mandatory Restaging (2-3 Weeks Post-Induction)

Critical decision point:

• Perform cystoscopy with bladder biopsy and cytology 1
• If complete response (CR): Proceed to consolidation therapy 1
• If residual invasive disease: Recommend immediate salvage cystectomy 1

Historical data shows 70-87% achieve CR after induction, with higher rates in T2 versus T3 disease 1, 3, 4

Phase 4: Consolidation Therapy (For CR Patients Only)

• Complete radiation to total dose of 64-65 Gy 1, 3
• Continue concurrent cisplatin during consolidation 3
• Additional boost to surgical bed if pT0 confirmed 1

Phase 5: Adjuvant Chemotherapy (Controversial)

While some protocols include adjuvant chemotherapy, the evidence is mixed:

• RTOG 97-06 showed only 45% of patients completed three cycles of MCV, indicating poor tolerance 5
• Gemcitabine-cisplatin adjuvant therapy showed 46% severe toxicity rate 4
• Recommendation: Consider adjuvant chemotherapy only in high-risk patients who have not received neoadjuvant chemotherapy, sandwiched between radiation cycles 1

Expected Outcomes

Efficacy data from major guidelines:

• 5-year overall survival: 50-67% 1, 6
• Bladder-intact survival at 5 years: 40-54% 1, 6
• Complete response rate: 70-87% 1, 3, 4
• Local control at 3 years: 73-96% with chemoradiation vs 69% with chemotherapy alone 1

Recurrence patterns:

• 20-30% develop new bladder lesions requiring additional treatment 1
• Approximately 25% require salvage cystectomy for persistent/recurrent disease 1

Surveillance Protocol

Intensive monitoring is mandatory:

• Cystoscopy with cytology every 3 months for first 2 years 1
• Then every 6 months thereafter 1
• Imaging of chest, abdomen, and pelvis every 3-12 months based on risk 2
• Upper tract imaging every 1-2 years for high-grade tumors 2

Salvage cystectomy criteria:

• Persistent invasive disease at any restaging 1
• Muscle-invasive recurrence during follow-up 1
• Progressive superficial disease not controlled by intravesical therapy 1

Common Pitfalls and Caveats

Understaging risk: Up to 45% of bladders may be clinically understaged after TURBT, with residual disease found at cystectomy 1. This underscores the importance of maximal initial resection and mandatory restaging.

Toxicity considerations:

• Grade 3/4 hematologic toxicity occurs in 10-14% during chemoradiation 1, 3
• Late grade ≥3 gastrointestinal toxicity is low with modern techniques 1
• Adjuvant chemotherapy causes severe toxicity in 32-46% of patients 5, 4

Patient selection errors: The most critical error is attempting bladder preservation in patients with hydronephrosis, which predicts poor outcomes 1. Similarly, T3b-T4 disease has significantly lower success rates than T2 disease 1.

Coordination requirement: This approach requires close multidisciplinary coordination between urology, radiation oncology, and medical oncology, with patient willingness to undergo lifelong surveillance 1