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Radiation Cystitis: a Contemporary Review

  • Cancer-Associated Voiding Dysfunction (S Elliott and J Pariser, Section Editors)
  • Published:
Current Bladder Dysfunction Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

There is not a universally agreed upon treatment algorithm for radiation cystitis. The goal of this review will be to discuss numerous options available to the provider at various points in treatment and the literature supporting its use.

Recent Findings

There are various degrees of presentation, with milder forms that can be managed as outpatient and more serious forms requiring inpatient admission. There are a myriad of treatment options, including intravesical instillations, ablative procedures, systemic therapies, hyperbaric oxygen therapy, arterial embolization, and urinary diversion. If these measures are able to control the bleeding in the acute setting, the patient can then be considered for outpatient systemic therapy to decrease the risk of hematuria recurrence. Hyperbaric oxygen therapy has emerged as an outpatient treatment option with very promising results; however, further research needs to evaluate its long-term cost-effectiveness.

Summary

Radiation cystitis is a devastating disease process that can occur months to years following radiotherapy and poses many therapeutic challenges. When conservative measures fail to control bladder hemorrhage, arterial embolization or urinary diversion may be ultimately necessary as life-saving measures, however, these are associated with considerable morbidity and mortality. Due to the devastating impact of radiation cystitis on patient quality of life, further research is imperative in order to add further innovative treatment strategies to our armamentarium.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Browne C, Davis NF, Maccraith E, et al. A narrative review on the pathophysiology and management for radiation cystitis. Adv Urol. 2015;2015:346812.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Pascoe C, Duncan C, Lamb BW, et al. Current management of radiation cystitis: a review and practical guide to clinical management. BJU Int. 2018.

  3. Gacci M, Saleh O, Giannessi C, et al. Bladder instillation therapy with hyaluronic acid and chondroitin sulfate improves symptoms of postradiation cystitis: prospective pilot study. Clin Genitourin Cancer. 2016;14(5):444–9.

    PubMed  Google Scholar 

  4. Giglio D, Wasén C, Mölne J, et al. Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder. Clin Exp Pharmacol Physiol. 2016;43(7):698–705.

    CAS  PubMed  Google Scholar 

  5. Ozdemir C, Akdis M, Akdis CA. T regulatory cells and their counterparts: masters of immune regulation. Clin Exp Allergy. 2009;39(5):626–39.

    CAS  PubMed  Google Scholar 

  6. Bonfili P, Franzese P, Marampon F, et al. Intravesical instillations with polydeoxyribonucleotides reduce symptoms of radiation-induced cystitis in patients treated with radiotherapy for pelvic cancer: a pilot study. Support Care Cancer. 2014;22(5):1155–9.

    PubMed  Google Scholar 

  7. Devries CR, Freiha FS. Hemorrhagic cystitis: a review. J Urol. 1990;143(1):1–9.

    CAS  PubMed  Google Scholar 

  8. • Mohan S, Kumar S, Dubey D, Phadke RV, Baijal SS, Kathuria M. Superselective vesical artery embolization in the management of intractable hematuria secondary to hemorrhagic cystitis. World J Urol. 2018. More studies such as these are necessary to further establish the role of arterial embolization in the setting of hemorrhagic cystitis, as most other studies within the literature are case reports or case series.

  9. Zagoria RJ, Hodge RG, Dyer RB, Routh WD. Percutaneous nephrostomy for treatment of intractable hemorrhagic cystitis. J Urol. 1993;149(6):1449–51.

    CAS  PubMed  Google Scholar 

  10. Sneiders A, Pryor JL. Percutaneous nephrostomy drainage in the treatment of severe hemorrhagic cystitis. J Urol. 1993;150(3):966–7.

    CAS  PubMed  Google Scholar 

  11. Park JC, Jung GS, Lee JH, Kim JK. Clinically intractable chronic unilateral hematuria: successful treatment with renal segmental artery embolization. Minim Invasive Ther Allied Technol. 2018;27(4):242–5.

    PubMed  Google Scholar 

  12. Korkmaz M, Şanal B, Aras B, et al. The short- and long-term effectiveness of transcatheter arterial embolization in patients with intractable hematuria. Diagn Interv Imaging. 2016;97(2):197–201.

    CAS  PubMed  Google Scholar 

  13. • Westerman ME, Boorjian SA, Linder BJ. Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation. Int Braz J Urol. 2016;42(6):1144–9. Most previous studies on alum were case reports with very small sample sizes. This study is one of the largest of its kind withn= 40.

    PubMed  PubMed Central  Google Scholar 

  14. Ho CC, Md Zainuddin Z. Alum irrigation for the treatment of intractable haematuria. Malays J Med Sci. 2009;16(4):66–8.

    PubMed  PubMed Central  Google Scholar 

  15. • Singh I, Laungani GB. Intravesical epsilon aminocaproic acid in management of intractable bladder hemorrhage. Urology. 1992;40(3):227–9. Most previous studies on amicar involved the oral formulation of the drug. This is one of the few studies that used it as an intravesical agent.

    CAS  PubMed  Google Scholar 

  16. Chuang YC, Yoshimura N, Wu M, et al. Intraprostatic capsaicin injection as a novel model for nonbacterial prostatitis and effects of botulinum toxin A. Eur Urol. 2007;51:1119–27.

    CAS  PubMed  Google Scholar 

  17. Chuang YC, Kim DK, Chiang PH, Chancellor MB. Bladder botulinum toxin A injection can benefit patients with radiation and chemical cystitis. BJU Int 2008;102(6):704–706.

    CAS  PubMed  Google Scholar 

  18. • Bove P, Iacovelli V, Tirindelli MC, et al. Endoscopic intravesical fibrin glue application in the treatment of refractory hemorrhagic radiation cystitis: a single cohort pilot study. J Endourol. 2018. This study is valuable as there are very few studies in the literature (aside from case reports) assessing the efficacy of intravesical fibrin glue application.

  19. Ziegelmann MJ, Boorjian SA, Joyce DD, Montgomery BD, Linder BJ. Intravesical formalin for hemorrhagic cystitis: a contemporary cohort. Can Urol Assoc J. 2017;11(3–4):E79–82.

    PubMed  PubMed Central  Google Scholar 

  20. •• Shao Y, Lu GL, Shen ZJ. Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation induced hemorrhagic cystitis. BJU Int. 2012;109(5):691–4. https://doi.org/10.1111/j.1464-410X.2011.10550.x. Given the significantly lower cost of hyaluronic acid compared to hyperbaric oxygen therapy, studies such as these are important to elucidate the most cost-effective treatment options for hemorrhagic cystitis.

    Article  PubMed  Google Scholar 

  21. Engles CD, Hauser PJ, Abdullah SN, Culkin DJ, Hurst RE. Intravesical chondroitin sulfate inhibits recruitment of inflammatory cells in an acute acid damage “leaky bladder” model of cystitis. Urology. 2012;79(2):483.e13–7.

    Google Scholar 

  22. Suzuki S, Chino A, Fukui I, et al. Successful use of endoscopic argon plasma coagulation for hemorrhagic radiation cystitis: a case report. Jpn J Clin Oncol. 2014;44(7):692–5.

    PubMed  Google Scholar 

  23. Martinez DR, Ercole CE, Lopez JG, Parker J, Hall MK. A novel approach for the treatment of radiation-induced hemorrhagic cystitis with the GreenLightTM XPS laser. Int Braz J Urol. 2015;41(3):584–7.

    PubMed  PubMed Central  Google Scholar 

  24. •• Talab SS, Mcdougal WS, Wu CL, Tabatabaei S. Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach. Urology. 2014;84(2):478–83. One of the largest studies looking at GreenLight laser in patients with radiation cystitis. The results are promising and suggest this may be a viable treatment option in the future.

    PubMed  Google Scholar 

  25. Zhu J, Xue B, Shan Y, Yang D, Zang Y. Transurethral coagulation for radiation-induced hemorrhagic cystitis using Greenlight™ potassium-titanyl-phosphate laser. Photomed Laser Surg. 2013;31(2):78–81.

    PubMed  Google Scholar 

  26. Ravi R. Endoscopic neodymium: YAG laser treatment of radiation-induced hemorrhagic cystitis. Lasers Surg Med. 1994;14:83–7.

    CAS  PubMed  Google Scholar 

  27. Stefanini M, English HA, Taylor AE. Safe and effective, prolonged administration of epsilon aminocaproic acid in bleeding from the urinary tract. J Urol. 1990;143(3):559–61.

    CAS  PubMed  Google Scholar 

  28. Liu YK, Harty JI, Steinbock GS, Holt HA, Goldstein DH, Amin M. Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen. J Urol. 1990;144(1):41–3.

    PubMed  Google Scholar 

  29. • Mousavi SA, Moazed V, Mohebbi N, et al. Conjugated estrogen in late-onset hemorrhagic cystitis associated with hematopoietic stem cell transplantation. Int J Hematol Oncol Stem Cell Res. 2017;11(1):13–8. The randomized design of this study gives weight to its significance, suggesting that perhaps 6.25 mg is an insufficient dose to achieve an effect with conjugated estrogens.

    PubMed  PubMed Central  Google Scholar 

  30. • Ordemann R, Naumann R, Geissler G, Bornhauser M, Schuler U, Ehninger G. Encouraging results in the treatment of haemorrhagic cystitis with estrogen - report of 10 cases and review of the literature. Bone Marrow Transplant. 2000;25(9):981–5. In contrast to Mousavi’s study, higher doses were used in this study and found to be more effective.

    CAS  PubMed  Google Scholar 

  31. Mougin J, Souday V, Martin F, Azzouzi AR, Bigot P. Evaluation of hyperbaric oxygen therapy in the treatment of radiation-induced hemorrhagic cystitis. Urology. 2016;94:42–6.

    Google Scholar 

  32. •• Dellis A, Papatsoris A, Kalentzos V, Deliveliotis C, Skolarikos A. Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis. Int Braz J Urol. 2017;43(3):489–95. A major strength of this study is that it excluded patients who received any other prior treatment for their radiation-induced hemorrhagic cystitis other than urethral catheterization, bladder irrigation, and/or blood transfusions. Most other studies did not do this and so probably have significant confounding bias.

    PubMed  PubMed Central  Google Scholar 

  33. •• Cardinal J, Slade A, Mcfarland M, Keihani S, Hotaling JN, Myers JB. Scoping review and meta-analysis of hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. Curr Urol Rep. 2018;19(6):38. The results of this meta-analysis are compelling, suggesting HBOT to be a highly effective systemic therapy option for radiation cystitis.

    PubMed  Google Scholar 

  34. Ribeiro de Oliveira TM, Carmelo Romão AJ, Gamito Guerreiro FM, Matos Lopes TM. Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol. 2015;22(10):962–6.

    CAS  PubMed  Google Scholar 

  35. Liss MA, Osann K, Cho J, Chua WC, Dash A. Severity of hematuria effects resolution in patients treated with hyperbaric oxygen therapy for radiation-induced hematuria. Urol Int. 2013;91(4):451–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Oscarsson N, Arnell P, Lodding P, Ricksten SE, Seeman-lodding H. Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: a prospective cohort study on patient-perceived quality of recovery. Int J Radiat Oncol Biol Phys. 2013;87(4):670–5.

    CAS  PubMed  Google Scholar 

  37. Sandhu SS, Goldstraw M, Woodhouse CR. The management of haemorrhagic cystitis with sodium pentosan polysulphate. BJU Int. 2004;94:845–7.

    PubMed  Google Scholar 

  38. Hampson SJ, Woodhouse CR. Sodium pentosanpolysulphate in the management of haemorrhagic cystitis: experience with 14 patients. Eur Urol. 1994;25:40–2.

    CAS  PubMed  Google Scholar 

  39. Matityahu A, Marmor M, Elson JK, et al. Acute complications of patients with pelvic fractures after pelvic angiographic embolization. Clin Orthop Relat Res. 2013;471(9):2906–11.

    PubMed  PubMed Central  Google Scholar 

  40. Tarkhanov A, Bartal G, Druzhin S, Shakhbazyan R, Grebenev E, Kartashov M. Bladder wall and surrounding tissue necrosis following bilateral superselective embolization of internal iliac artery branches due to uncontrollable haematuria related to bladder tumor: case report. CVIR Endovasc. 2018;1(1):34.

    PubMed  PubMed Central  Google Scholar 

  41. Ali A, Nabi G, Swami S, Somani B. Bladder necrosis secondary to internal iliac artery embolization following pelvic fracture. Urol Ann. 2014;6(2):166–8.

    PubMed  PubMed Central  Google Scholar 

  42. Sieber PR. Bladder necrosis secondary to pelvic artery embolization: case report and literature review. J Urol. 1994;151(2):422.

    CAS  PubMed  Google Scholar 

  43. Washington S, Osterberg EC, Elliott SP, Hittelman AB, Breyer BN. Acute bladder necrosis after pelvic arterial embolization for pelvic trauma: lessons learned from two cases of immediate postembolization bladder necrosis. Case Rep Urol. 2016;2016:7594192.

    PubMed  PubMed Central  Google Scholar 

  44. •• Linder BJ, Tarrell RF, Boorjian SA. Cystectomy for refractory hemorrhagic cystitis: contemporary etiology, presentation and outcomes. J Urol. 2014;192(6):1687–92. This study clearly demonstrates the high perioperative morbidity and mortality associated with cystectomy, and establishes this as a treatment of last resort.

    PubMed  Google Scholar 

  45. Soler R, Vianello A, Füllhase C, et al. Vascular therapy for radiation cystitis. Neurourol Urodyn. 2011;30(3):428–34.

    PubMed  Google Scholar 

  46. Rajaganapathy BR, Janicki JJ, Levanovich P, et al. Intravesical liposomal tacrolimus protects against radiation cystitis induced by 3-beam targeted bladder radiation. J Urol. 2015;194(2):578–84.

    CAS  PubMed  Google Scholar 

  47. Chuang Y, Tyagi P, Huang H, et al. Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide-induced inflammatory cystitis. Neurourol Urodyn. 2011;30:421–7.

    CAS  PubMed  Google Scholar 

  48. Dave CN, Chaus F, Chancellor MB, Lajness M, Peters KM. Innovative use of intravesical tacrolimus for hemorrhagic radiation cystitis. Int Urol Nephrol. 2015;47(10):1679–81.

    CAS  PubMed  Google Scholar 

  49. Giglio D, Podmolíková L, Tobin G. Changes in the neuronal control of the urinary bladder in a model of radiation cystitis. J Pharmacol Exp Ther. 2018;365(2):327–35.

    CAS  PubMed  Google Scholar 

  50. Osti MF, Nicosia L, Agolli L, et al. Potential role of single nucleotide polymorphisms of XRCC1, XRCC3, and RAD51 in predicting acute toxicity in rectal cancer patients treated with preoperative radiochemotherapy. Am J Clin Oncol. 2017;40(6):535–42.

    CAS  PubMed  Google Scholar 

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  1. Department of Urology, Lahey Hospital and Medical Center, 41 Burlington Mall Rd, Burlington, MA, 01801, USA

    Kareem Alazem, Jaime A. Cavallo & Alex J. Vanni

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  1. Kareem Alazem
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Correspondence to Alex J. Vanni.

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Alazem, K., Cavallo, J.A. & Vanni, A.J. Radiation Cystitis: a Contemporary Review. Curr Bladder Dysfunct Rep 14, 246–255 (2019). https://doi.org/10.1007/s11884-019-00538-3

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