Role of Aktocyte in Radiation-Induced Cystitis
There is currently no established role for Aktocyte (autologous cellular therapy) in the treatment of radiation-induced cystitis based on current clinical guidelines and evidence.
Pathophysiology of Radiation-Induced Cystitis
- Radiation-induced cystitis results from damage to bladder vasculature and smooth muscle fibers, causing edema, cell death, and fibrosis 1, 2
- Acute symptoms typically occur after a dose of 20 Gy to the bladder and include dysuria, urinary frequency, nocturia, and hesitancy 1, 2
- Chronic symptoms develop with a latency period of 1-25 years due to progressive vascular endothelial cell damage 2
- Approximately 50% of women experience acute urinary symptoms after pelvic radiotherapy for gynecologic malignancies 1
- Late complications include hemorrhagic cystitis (5-9%), reduced bladder capacity, and rarely vesicovaginal and ureterovaginal fistulas 1
Risk Factors
- History of abdominal surgery, pelvic inflammatory disease, hypertension, diabetes mellitus, and smoking increase risk of late genitourinary toxicity 1, 2
- Older age significantly impacts incontinence risk due to potentially higher bladder neck doses 1, 2
- Obesity and overweight are risk factors for urinary incontinence and frequency 1, 2
Current Treatment Approaches
First-Line Management
- Hydration, non-steroidal anti-inflammatory drugs, and anticholinergic agents for low-grade symptoms 1, 2
- Adequate hydration is crucial to dilute toxic metabolites in the urine 2
- Initial workup should include urine analysis and culture to rule out infection 2
Second-Line Interventions
- Botulinum toxin A injection into the detrusor muscle when drug therapy is ineffective 1, 2
- Hyperbaric oxygen therapy, which induces neo-vascularization, tissue re-oxygenation, and fibroblast proliferation, has shown promising results in treating radiation-induced cystitis 1, 2, 3
- For hemorrhagic cystitis: clot evacuation, endoscopic fulguration, and bladder irrigation 1, 2
Refractory Cases
- Surgical intervention should be evaluated in cases of refractory disease 2
- Options include percutaneous nephrostomy, ureteral stent placement, and ileal ureteral substitution 1, 2
- In rare cases, urinary diversion with or without cystectomy may be necessary 4
Prevention Strategies
- Different IMRT modalities may reduce the rate of acute and late high-grade urinary toxicity 1, 2
- To reduce severe urinary complications, a D2cm³ ≤ 80 Gy EQD2 should be used 1, 2
- Dose to the bladder trigone should be minimized as it is predictive of severe late urinary toxicity 2
Emerging Therapies
- While several novel therapies are being investigated for radiation-induced cystitis, Aktocyte (autologous cellular therapy) is not mentioned in any of the current guidelines or research evidence 2, 5, 3
- Intravesical immunosuppression with local tacrolimus formulation is being developed for treatment of radiation hemorrhagic cystitis 5
- Mesenchymal stromal cell therapy is under investigation in prospective studies 3
Clinical Considerations
- The management of radiation-induced cystitis requires a tailored approach based on symptom severity 2
- Infection and primary bladder malignancy must be ruled out in patients with persistent symptoms 2
- Regular monitoring of renal function is necessary, especially in patients with pre-existing renal impairment 2
- Most patients ultimately require multimodal treatment for curative purposes 6