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Radiation Cystitis Treatment & Management

  • Author: Nicolas A Muruve, MD, FACS, FRCSC; Chief Editor: Edward David Kim, MD, FACS  more...
 
Updated: Nov 09, 2014
 

Approach Considerations

Indications for treatment depend on the degree of symptoms present and the patient's sense of need to be treated. Grade 1 and 2 symptoms need treatment only if the patient is bothered by them. These can be managed medically. Observation is acceptable. Management of grade 3 and higher clinical presentations depends on the type of symptom. Voiding dysfunction can be managed medically if the patient desires.

Fistula formation usually requires surgical intervention. Contracted bladder and incontinence require evaluation to determine the degree of disability, bladder compromise, and potential need for surgery.

The use of endoscopic injection sclerotherapy has been reported with good results in a limited number of patients with intractable hemorrhagic cystitis.[8] This treatment involves the injection of a sclerosing agent (eg, 1% ethoxysclerol) into the bleeding areas to control the severe hematuria in patients with otherwise intractable bleeding that is not responding to simpler methods. Further studies are necessary to determine the exact role of this novel type of therapy in selected patients with radiation cystitis.

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Pharmacologic Therapy

Symptomatic frequency and urgency are best treated with anticholinergic agents. Once all other causes of dysuria have been ruled out, phenazopyridine can be used to provide symptomatic relief.

If the symptoms of radiation cystitis are not severe but are significant enough for a patient to seek help, pentosan polysulfate sodium (Elmiron), with or without pentoxifylline for pain, is a reasonable first step.[9, 10]

If symptoms become more severe or oral therapy is not satisfactory, the available literature suggests that hyperbaric oxygen (HBO) therapy yields the most consistent results.[11]

Prevention

Prophylaxis against the development of radiation cystitis has been reported with the use of the antioxidant orgotein prior to undergoing radiation therapy.[12] Dimethyl sulfoxide (DMSO) has also been described as having a radioprotective effect. However, few studies have evaluated its use in human bladders.

The use of antioxidant therapy follows the theory that healthy tissues are damaged by free radicals produced within the target cell and then released into the extracellular space. The free radical is then allowed to travel to normal cells, where it causes damage and clinically produces toxicity. Free-radical scavengers normally exist intracellularly and thus are not found in the extracellular space. By administering exogenous free radical scavengers, the intent is to decrease collateral damage to cells by picking up the extracellular free radicals.

Note that these agents may also prevent collateral cell damage within the tumors themselves. This could potentially decrease the effectiveness of anticancer therapy. Although reports exist of decreased toxicity with these agents, few reports exist on overall disease control with antioxidant therapy. One study of antioxidant therapy for oral tumors does show decreased toxicity with comparable tumor control rates.[13] However, the study was small and involved a multimodality therapy, which may have contributed to the good results. Antioxidants require further study before they are put into widespread use.

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Hyperbaric Oxygen Therapy

Therapy for radiation cystitis is primarily aimed at relief of symptoms. The exception is HBO therapy, which can potentially reverse the changes caused by radiation. HBO therapy stimulates angiogenesis, which reverses the vascular changes induced by ionizing radiation.[14] The ability of HBO to preserve bladder function and the noninvasive nature of this treatment are features that favor its use. However, if significant fibrosis and ischemia have already occurred, HBO therapy does not reverse the changes and only prevents further injury.[15, 16]

HBO therapy has a reported response rate of 27-92%, and the recurrence rate is 8-63%.[17] In adults, HBO is administered as 100% oxygen at 2-2.5atm. Each session lasts from 90-120 minutes, and patients receive HBO sessions 5 days weekly for a total of 40-60 sessions. HBO therapy is a pregnancy category A treatment.

Nakada and colleagues reported good long-term outcomes with HBO treatment in 38 patients with radiation cystitis following irradiation of prostate cancer. At 7-year follow-up, objective and subjective improvements in symptoms were seen in 72-83% of patients. No recurrence was seen in 28 patients (74%); these patients had received an 18% lower radiation dose than patients who did experience recurrence.[18]

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Indications for Surgery

Surgery is reserved for the management of severe complications that do not respond to medical management. Indications for surgery include the following:

  • Ongoing gross hematuria that does not respond to bladder irrigations or that requires numerous transfusions
  • Small, contracted bladder with incontinence or severe frequency
  • Specific complications of radiation (eg, fistulas, hydronephrosis, strictures)

Surgical options for small-volume bladder include bladder augmentation, urinary diversion, and cystectomy.

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Treatment of Hemorrhagic Cystitis

Hemorrhagic cystitis is a more serious complication of radiation cystitis. Cystoscopy is useful in the initial management, both diagnostically to rule out other pathology and for clot evacuation if bleeding is heavy. This can resolve symptoms in up to 61% of patients at initial presentation.

If bleeding is severe, bladder irrigation may be started either alone or in conjunction with hyperbaric therapy. Start continuous bladder irrigation alone first. If this is not successful, try bladder instillation. In order of increasing toxicity, these agents include 1% alum, aminocaproic acid (Amicar), and 1-10% formalin.[19, 20, 21, 22, 23, 24, 25] Other options are oral pentosan polysulfate sodium, HBO therapy, and oral estrogens.[26] If symptoms persist, however, cystoscopic intervention is rarely successful.[27]

Surgical options for hemorrhagic cystitis include the following:

  • Cystoscopy and fulguration
  • Percutaneous nephrostomy tube insertions
  • Internal iliac artery embolization
  • Surgical diversion
  • Cystectomy

Cystectomy for hemorrhagic cystitis is associated with high rates of perioperative complications and mortality. It should be used only after more conservative approaches have been attempted.[28]

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Contributor Information and Disclosures
Author

Nicolas A Muruve, MD, FACS, FRCSC Associate Staff, Department of Urology, Cleveland Clinic Florida

Nicolas A Muruve, MD, FACS, FRCSC is a member of the following medical societies: American College of Surgeons, Society of Urologic Oncology, Canadian Urological Association, American Society of Transplant Surgeons, American Urological Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, Tennessee Medical Association, Sexual Medicine Society of North America, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Repros.

Acknowledgements

Michael Grasso III, MD Director of Endourology, Lenox Hill Hospital; Professor and Vice Chairman, Department of Urology, New York Medical College

Michael Grasso III, MD is a member of the following medical societies: American Medical Association, American Urological Association, Endourological Society, Medical Society of the State of New York, National Kidney Foundation, Société Internationale d'Urologie (International Society of Urology), and Society of Laparoendoscopic Surgeons

Disclosure: Karl Storz Endoscopy Consulting fee Consulting; Boston Scientific Consulting fee Consulting; Cook Urologic Consulting fee Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership

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Cystoscopic view of a bladder showing the neovascularity and telangiectasia of radiation cystitis.
Cystoscopic view of a bladder showing the neovascularity and telangiectasia of radiation cystitis.
Cystoscopic view of a radiated bladder showing areas of neovascularization next to an area of pallor; the pallor was caused by increased collagen deposition. In such cases, the collagen prevents new vessels from forming in injured areas and contributes to ischemia.
 
 
 
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