eMedicine Specialties > Urology > Infections and Related Inflammatory Conditions

Radiation Cystitis: Treatment

Author: Nicolas A Muruve, MD, FRCSC, FACS, Associate Staff, Department of Urology, Cleveland Clinic Florida
Contributor Information and Disclosures

Updated: Jun 1, 2009

Treatment

Medical Therapy

Therapy is primarily aimed at relief of symptoms. The exception is hyperbaric oxygen (HBO) therapy. Treatment with HBO can potentially reverse the changes caused by radiation. HBO therapy stimulates angiogenesis, which reverses the vascular changes induced by ionizing radiation. Preservation of bladder function and the noninvasive nature of treatment (30 sessions total) favor its use. Some reports claim 70% response with HBO. However, if significant fibrosis and ischemia have already occurred, HBO therapy does not reverse the changes and only prevents further injury.

Symptomatic frequency and urgency are best treated with anticholinergic agents.

Once all other causes of dysuria have been ruled out, phenazopyridine hydrochloride can be used to provide symptomatic relief.

Hemorrhagic cystitis is a more serious complication of radiation cystitis. Once all clots have been evacuated and adequate drainage achieved, medical options to control the bleeding include continuous bladder irrigation alone, a 1% alum bladder installation, a 1%-10% formalin bladder installation, aminocaproic acid (Amicar) bladder installation, sodium pentosanpolysulphate, HBO therapy, and oral estrogens.

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

The concept of using antioxidant therapy involves 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 then 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 tumors themselves. This could potentially decrease the effectiveness of anticancer therapy. Although reports exist of decreased toxicity with these agents, few report on overall disease control with antioxidant therapy compared to controls. One study looking at antioxidant therapy for oral tumors does show decreased toxicity with comparable tumor control rates.² However, the study was small and involved a multimodality therapy, which may have contributed to their good results. Antioxidants require further study before they are put into widespread use.

Reported responses to treatments are as follows:

Drug Name - HBO therapy - Reported response rate is 27%-92%, and recurrence rate is 8%-63%.
Adult Dose - Administer as 100% oxygen at 2-2.5 atm; each lasts from 90-120 min administered 5 d/wk for a total of 40-60 sessions
Contraindications - Viral infection, absolute contraindication (can cause widespread viremia); partial pressure of carbon dioxide (PCO2) >60 mm Hg and pneumothorax, relative contraindications; history of ear surgery with inability to decompress the middle ear space; vitamin E deficiency; massive doses of ASA, vitamin C, or steroids (enhances likelihood of CNS oxygen toxicity); vitamin E deficiency, massive doses of ASA, vitamin C, or steroids (enhances likelihood of CNS oxygen toxicity)
Interactions - None reported
Pregnancy - A - Fetal risk not revealed in controlled studies in humans
Precautions - Adverse effects are oxygen toxicity, which is rare (eg, seizures and alveolar membrane damage), confinement anxiety, ear pain, and digitalis toxicity (if taking drug); must be vented via a chest tube prior to pressurizing COPD; severe emphysematous changes can lead to spontaneous pneumothorax or congenital spherocytosis; HBO may increase RBC fragility; in pregnancy, use only in life-threatening situations; patients with epilepsy must be sedated because oxygen is a CNS stimulant; in fever of unknown origin, must find etiology before treating

Drug Name - Sodium pentosanpolysulphate (Elmiron) - Response rate is 71%-100%, and recurrence rate is 23%. Protects transitional epithelium by restoring the bladder glycosaminoglycan layer.
Adult Dose - 100 mg PO tid until symptoms resolve; minimum of 4 wk
Contraindications - Documented hypersensitivity
Interactions - May increase effect of anticoagulants
Pregnancy - B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions - Adverse effects, including diarrhea, nausea, alopecia (reversible upon discontinuation), headache, rash, dyspepsia, abdominal pain, liver function abnormalities, and dizziness, occurred at a frequency of 1%-4%

Drug Name - Formalin - A 37% solution of formaldehyde and water. Response rate is 52%-89%, and recurrence rate is 20%-25%. Mechanism of action is tissue fixative.
Adult Dose - Local: 5% formalin pledgets are placed endoscopically on bleeding points for 15 min, then removed
Bladder irrigation: 1%-10% solution (4% preferred); manually fill bladder to capacity under gravity (catheter <15 cm above symphysis pubis); contact time ranges from 14 min for 10% solution to 23 min for 5% solution; this is a painful procedure and requires a general anesthetic
Contraindications - Vesicoureteric reflux and bladder rupture or leak (use with caution in a patient with a recent bladder biopsy)
Interactions - None reported
Pregnancy - C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions - Preprocedure cystography to rule out reflux reduces the incidence of complications, which include pain, vesicoureteric reflux, fever, tachycardia, uremia and renal insufficiency, hydronephrosis, voiding dysfunction, fistula, papillary necrosis, and decreased bladder capacity

Drug Name - Alum - Response rate is 50-80%, and the recurrence rate is 10%. Alum causes protein precipitation in the interstitial spaces and cell membranes, causing contraction of extracellular matrix and tamponade of bleeding vessels. Exposed capillary epithelium is also sclerosed.
Adult Dose - 1% solution prepared by mixing 50 g of potassium aluminum sulfate in 5 L of distilled water; run intravesically at a rate of 3-5 mL/min and increase to a maximum of 10 mL/min if returns are not clear; continue for 6 h after bleeding stops
Contraindications - Renal failure (aluminum is excreted by the kidneys, and patients with renal failure are at risk for development of aluminum toxicity)
Interactions - None reported
Pregnancy - C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions - Complications are increased PT, aluminum toxicity (eg, encephalopathy, dementia, speech disorders, osteomalacia, aplastic bone disease [chronic exposure associated with painful spontaneous fractures, hypercalcemia, and tumorous calcinosis]), proximal myopathy, increased risk of infection, increased left ventricular mass and decreased myocardial function, microcytic anemia with very high levels, and sudden death

Drug Name - Aminocaproic acid (Amicar) - Response rate is 91%, and recurrences are not reported. Antifibrinolytic agent that inhibits plasminogen activation, thus decreasing plasmin.
Adult Dose - 200 mg of aminocaproic acid in 1 L of isotonic sodium chloride solution; run intravesically according to severity of bleeding and continue for 24 h after bleeding stops
Contraindications - Active intravascular clotting process or DIC
Interactions - Coadministration with estrogens may cause increase in clotting factors, leading to a hypercoagulable state
Pregnancy - C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions - When administered intravesically, systemic complications are reduced; these include thrombosis, obstruction of ureters with clot, hypotension, cardiac arrhythmias, and rhabdomyolysis

Drug Name - Conjugated estrogens (Premarin) - Response rate is 100%, and recurrence rate is 20% (1 report of 5 patients only). Mechanism of action is unknown. In patients with renal failure, estrogen has been reported to correct prolonged bleeding time. However, in radiation cystitis complications, bleeding time is usually normal.
Adult Dose - 5 mg/d PO for 4-7 d
Contraindications - Known or suspected pregnancy; undiagnosed abnormal genital bleeding; known or suggested breast cancer; known or suggested estrogen-dependent neoplasia; active thrombophlebitis or thromboembolic disorders; documented hypersensitivity
Interactions - May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic P450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins
Pregnancy - X - Contraindicated; benefit does not outweigh risk
Precautions - Complications are thromboembolism, breast and uterine cancer (prolonged exposure), cholelithiasis, pancreatitis, nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice, erythema multiforme, erythema nodosum, hemorrhagic eruption, alopecia, hirsutism, headache, migraine, dizziness, mental depression, chorea, aggravation of porphyria, edema, and changes in libido

Drug Name - Pentoxifylline (Trental) - Pain relief from radiation fibrosis has also been reported with pentoxifylline. Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. This increases blood flow to the affected microcirculation and enhances tissue oxygenation. The precise mode of action of pentoxifylline and the sequence of events leading to clinical improvement remain undefined.
Adult Dose - 400 mg PO tid for 6 wk
Contraindications - Recent cerebral and/or retinal hemorrhage; previously exhibited intolerance to this product or methylxanthines such as caffeine, theophylline, and theobromine
Interactions - Coadministration with cimetidine or theophylline, increases effect/toxic potential; pentoxifylline increases effect of antihypertensives
Pregnancy - C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions - Adverse effects are chest pain, arrhythmias, drowsiness, flushing, dizziness, irritability, tremor, convulsions, dizziness, headache, nausea or vomiting, and abdominal pain

If the symptoms of radiation cystitis are not severe but significant enough for a patient to seek help, sodium pentosanpolysulphate with or without pentoxifylline for pain is a reasonable first step. If symptoms become more severe or oral therapy is not satisfactory, HBO therapy, based on the available literature, appears to yield the most consistent results.

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 the next least toxic agent. In order, these agents include alum, aminocaproic acid, and formalin.

Surgical Therapy

Cystoscopy is useful in the initial management of radiation cystitis, 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. However, if symptoms persist, cystoscopic intervention is rarely successful.³

Surgery is reserved for the management of severe complications that do not respond to medical management. Indications for surgery include ongoing gross hematuria that does not respond to bladder irrigations or that require numerous transfusions, small contracted bladder with incontinence or severe frequency, and specific complications of radiation (eg, fistulas, hydronephrosis, strictures).

Surgical options for hemorrhagic cystitis include cystoscopy and fulguration, percutaneous nephrostomy tube insertions, internal iliac artery embolization, surgical diversion, and cystectomy.

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

Follow-up

Follow-up care for radiation cystitis is generally supportive. Symptoms can be recurrent or even persistent, as in the case of dysfunctional voiding. Because symptomatic manifestations of radiation cystitis can occur many years after primary radiation therapy, regular clinical follow-up care and good communication with patients are essential.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Bladder Cancer and Blood in the Urine.

Complications

Complications of radiation cystitis include hemorrhagic cystitis (3%-5%), vesical fistula (2%), and bladder neck contracture (3%-5%). Neoplasia and contracted bladder can also occur but are rare.

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