Radiation Cystitis Treatment & Management
- Author: Nicolas A Muruve, MD, FACS, FRCSC; Chief Editor: Edward David Kim, MD, FACS more...
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. 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.
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.
Prophylaxis against the development of radiation cystitis has been reported with the use of the antioxidant orgotein prior to undergoing radiation therapy. 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. 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.
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. 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%. 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.
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)
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. If symptoms persist, however, cystoscopic intervention is rarely successful.
Surgical options for hemorrhagic cystitis include the following:
Cystoscopy and fulguration
Percutaneous nephrostomy tube insertions
Internal iliac artery embolization
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.
Cancer Facts & Figures 2014. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed: October 30, 2014.
Nonaka T, Nakayama Y, Mizoguchi N, et al. Definitive radiation therapy for invasive carcinoma of the vagina: impact of high-dose rate intracavitary brachytherapy. Int J Clin Oncol. 2012 Feb 7. [Medline].
Pilepich MV, Krall J, George FW, Asbell SO, Plenk HD, Johnson RJ, et al. Treatment-related morbidity in phase III RTOG studies of extended-field irradiation for carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 1984 Oct. 10(10):1861-7. [Medline].
Perez CA, Grigsby PW, Lockett MA, Chao KS, Williamson J. Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation. Int J Radiat Oncol Biol Phys. 1999 Jul 1. 44(4):855-66. [Medline].
Lips IM, Dehnad H, van Gils CH, Boeken Kruger AE, van der Heide UA, van Vulpen M. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients. Radiat Oncol. 2008 May 21. 3:15. [Medline]. [Full Text].
Kim SY, Hong YS, Kim DY, et al. Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with locally advanced resectable rectal cancer: a multicenter phase II study. Int J Radiat Oncol Biol Phys. 2011 Nov 1. 81(3):677-83. [Medline].
Goldman SM, Fishman EK, Gatewood OM, Jones B, Siegelman SS. CT in the diagnosis of enterovesical fistulae. AJR Am J Roentgenol. 1985 Jun. 144(6):1229-33. [Medline].
Tunuguntla HS, Bhandari M, Srivastava A, Kapoor R, Saha TK. Endoscopic injection sclerotherapy control of intractable hematuria following radiation-induced hemorrhagic cystitis. A novel approach. Arch Esp Urol. 2000 May. 53(4):396-402. [Medline].
Parsons CL. Successful management of radiation cystitis with sodium pentosanpolysulfate. J Urol. 1986 Oct. 136(4):813-4. [Medline].
Sandhu SS, Goldstraw M, Woodhouse CR. The management of haemorrhagic cystitis with sodium pentosan polysulphate. BJU Int. 2004 Oct. 94(6):845-7. [Medline].
Weiss JP, Mattei DM, Neville EC, Hanno PM. Primary treatment of radiation-induced hemorrhagic cystitis with hyperbaric oxygen: 10-year experience. J Urol. 1994 Jun. 151(6):1514-7. [Medline].
Sanchiz F, Millá A, Artola N, Julià JC, Moya LM, Pedro A, et al. Prevention of radioinduced cystitis by orgotein: a randomized study. Anticancer Res. 1996 Jul-Aug. 16(4A):2025-8. [Medline].
Osaki T, Ueta E, Yoneda K, Hirota J, Yamamoto T. Prophylaxis of oral mucositis associated with chemoradiotherapy for oral carcinoma by Azelastine hydrochloride (Azelastine) with other antioxidants. Head Neck. 1994 Jul-Aug. 16(4):331-9. [Medline].
Neheman A, Nativ O, Moskovitz B, Melamed Y, Stein A. Hyperbaric oxygen therapy for radiation-induced haemorrhagic cystitis. BJU Int. 2005 Jul. 96(1):107-9. [Medline].
Allen S, Kilian C, Phelps J, et al. The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence. Support Care Cancer. 2012 Jan 14. [Medline].
Hampson NB, Holm JR, Wreford-Brown CE, et al. Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury. Cancer. 2011 Dec 2. [Medline].
Del Pizzo JJ, Chew BH, Jacobs SC, Sklar GN. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term followup. J Urol. 1998 Sep. 160(3 Pt 1):731-3. [Medline].
Nakada T, Nakada H, Yoshida Y, Nakashima Y, Banya Y, Fujihira T, et al. Hyperbaric oxygen therapy for radiation cystitis in patients with prostate cancer: a long-term follow-up study. Urol Int. 2012. 89(2):208-14. [Medline].
Dewan AK, Mohan GM, Ravi R. Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix. Int J Gynaecol Obstet. 1993 Aug. 42(2):131-5. [Medline].
Donahue LA, Frank IN. Intravesical formalin for hemorrhagic cystitis: analysis of therapy. J Urol. 1989 Apr. 141(4):809-12. [Medline].
Goswami AK, Mahajan RK, Nath R, Sharma SK. How safe is 1% alum irrigation in controlling intractable vesical hemorrhage?. J Urol. 1993 Feb. 149(2):264-7. [Medline].
Likourinas M, Cranides A, Jiannopoulos B, Kostakopoulos A, Dimopoulos C. Intravesical formalin for the control of intractable bladder haemorrhage secondary to radiation cystitis or bladder cancer. Urol Res. 1979 Jun 22. 7(2):125-6. [Medline].
Lowe BA, Stamey TA. Endoscopic topical placement of formalin soaked pledgets to control localized hemorrhage due to radiation cystitis. J Urol. 1997 Aug. 158(2):528-9. [Medline].
Nurmi M, Puntala P, Torniainen K. Alum irrigation in the treatment of severe haemorrhage from the bladder. Ann Chir Gynaecol. 1987. 76(3):173-5. [Medline].
Singh I, Laungani GB. Intravesical epsilon aminocaproic acid in management of intractable bladder hemorrhage. Urology. 1992 Sep. 40(3):227-9. [Medline].
Liu YK, Harty JI, Steinbock GS, Holt HA Jr, Goldstein DH, Amin M. Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen. J Urol. 1990 Jul. 144(1):41-3. [Medline].
Kaplan JR, Wolf JS Jr. Efficacy and survival associated with cystoscopy and clot evacuation for radiation or cyclophosphamide induced hemorrhagic cystitis. J Urol. 2009 Feb. 181(2):641-6. [Medline].
Linder BJ, Tarrell RF, Boorjian SA. Cystectomy for Refractory Hemorrhagic Cystitis: Contemporary Etiology, Presentation and Outcomes. J Urol. 2014 Jun 14. [Medline].
Hampson SJ, Woodhouse CR. Sodium pentosanpolysulphate in the management of haemorrhagic cystitis: experience with 14 patients. Eur Urol. 1994. 25(1):40-2. [Medline].