What is the treatment approach for a patient with hemorrhagic cystitis, particularly those undergoing chemotherapy or radiation therapy?

Treatment of Hemorrhagic Cystitis in Chemotherapy and Radiation Patients

For chemotherapy-induced hemorrhagic cystitis, prevention with mesna and aggressive hydration is paramount, while established bleeding requires a stepwise approach starting with conservative management (hydration, bladder irrigation, symptom control) before escalating to interventional therapies. 1

Prevention Strategies (Critical First-Line Approach)

For Chemotherapy Patients

Mesna administration is the cornerstone of prevention when using cyclophosphamide or ifosfamide, as it binds the toxic metabolite acrolein that causes bladder damage. 1

• For ifosfamide: Give IV mesna bolus at 20% of the ifosfamide dose at time of administration, followed by oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each dose (total daily mesna = 100% of ifosfamide dose). 1
• For high-dose cyclophosphamide (≥1500 mg/m²/day): Use mesna plus saline diuresis or forced saline diuresis, particularly in stem-cell transplantation settings. 1
• Critical caveat: If the patient vomits within 2 hours of oral mesna, repeat the dose or switch to IV mesna. 1

Hydration and Bladder Emptying Protocol

• Maintain aggressive hydration: 2-3 liters in 24 hours to dilute toxic metabolites. 1
• Forced diuresis: >8 glasses of water daily with frequent bladder emptying throughout treatment. 1
• Morning void is critical: Instruct patients to urinate immediately upon waking to prevent acrolein from dwelling in the bladder overnight. 1
• Monthly monitoring: Check urine for red blood cells in patients on cyclophosphamide. 1

Diagnostic Evaluation

Before initiating treatment, establish the diagnosis and severity:

• Check vital signs, hemoglobin, hematocrit, and coagulation parameters to assess bleeding severity. 1
• Perform urine analysis and culture to exclude infection as the primary cause. 1
• Digital rectal examination and cystoscopy (flexible sigmoidoscopy if bright red blood) to rule out other causes of hematuria and assess for radiation-induced telangiectasia. 2
• Important: Do NOT biopsy irradiated mucosa unless neoplastic or inflammatory processes are suspected, as this carries risk of fistula or necrosis. 2

Treatment Algorithm for Established Hemorrhagic Cystitis

Step 1: Conservative Management (First-Line)

Most patients with mild to moderate bleeding can be managed conservatively without intervention. 2, 1

• Hydration with forced diuresis and frequent bladder emptying to reduce bladder toxicity. 1
• Continuous bladder irrigation with indwelling catheter for macroscopic hematuria to prevent clot formation. 2, 3
• Pain management: NSAIDs for symptomatic relief. 1
• Anticholinergic agents (e.g., oxybutynin) for urinary irritative symptoms. 1
• Reassurance and explanation: Many patients with radiation-induced bleeding have minor, intermittent symptoms that do not require intervention beyond observation. 2

Step 2: Optimize Modifiable Factors

For radiation-induced hemorrhagic cystitis specifically:

• Stop anticoagulants/antiplatelet agents if possible, which often reduces bleeding to a level that no longer affects quality of life. 2
• Optimize irregular bowel function, as this will often reduce bleeding from radiation-induced telangiectasia. 2

Step 3: Intravesical Therapies

Sucralfate enemas can serve as temporary treatment for heavy bleeding or long-term therapy for those unsuitable for definitive interventions. 2

Sucralfate enema protocol (for radiation-induced bleeding):

• Mix 2g sucralfate suspension with 30-50 mL tap water 2
• Administer via soft Foley catheter into rectum 2
• Patient should roll 360 degrees to coat entire rectal surface, lying prone to best cover anterior wall telangiectasia 2
• Retain for 20 minutes if possible 2
• Use twice daily initially; may reduce to once daily for maintenance 2
• Caveat: Bleeding likely recurs when treatment is stopped 2

Step 4: Advanced Interventions

When conservative measures fail and bleeding significantly affects quality of life or causes transfusion-dependent anemia:

• Endoscopic fulguration/cauterization of bleeding mucosal areas for localized bleeding sites. 3, 4
• Botulinum toxin A injection into the detrusor muscle when drug therapy is ineffective. 1
• Hyperbaric oxygen therapy: A 1999 study showed complete resolution in 64% of radiation-induced hemorrhagic cystitis patients (mean 14 treatments), with long-term remission in the majority. 5 However, a 2025 guideline notes contradictory data from randomized trials, with the underpowered HOT2 study showing no statistically significant benefit. 2
• Arterial embolization of pelvic vessels in selected life-threatening cases. 3, 4

Step 5: Salvage Surgery

Cystectomy is reserved only for life-threatening hemorrhage unresponsive to all other measures. 3, 4

Special Considerations for BCG-Induced Hemorrhagic Cystitis

For patients receiving BCG therapy who develop hematuria:

• Perform urine culture to exclude hemorrhagic cystitis from infection. 2
• Postpone BCG instillation until urine is clear. 2
• If macrohematuria occurs: Place indwelling catheter with continuous bladder irrigation; perform endoscopic hemostasis if necessary. 2
• If hematuria persists: Perform cystoscopy to evaluate for bladder tumor recurrence. 2

Monitoring During Treatment

• Monitor urine output and appearance for signs of ongoing or worsening hematuria. 1
• Regular renal function assessment, especially in patients with pre-existing renal impairment. 1
• Watch for signs of infection, as hemorrhagic cystitis predisposes to urinary tract infections. 1
• Serial hemoglobin checks in patients with persistent bleeding. 1

Critical Pitfalls to Avoid

• Do not perform aspiration, sclerotherapy, or laparoscopic procedures during active intracystic hemorrhage from any cause—conservative management is preferred. 2
• Avoid steroids in patients receiving tumor-infiltrating lymphocyte (TIL) therapy, as they may adversely affect the infused cells. 1
• Do not assume all bleeding is from radiation or chemotherapy—up to half of patients with rectal bleeding after pelvic radiotherapy have other causes requiring full endoscopic evaluation. 2
• Early application of hyperbaric oxygen (when chosen) is associated with earlier resolution compared to delayed treatment. 5