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Radiation and Hemorrhagic Cystitis

Radiation cystitis is late injury of the bladder after pelvic radiotherapy, expressed as storage symptoms, reduced capacity and compliance, and bleeding from fragile, telangiectatic urothelium. Hemorrhagic cystitis is diffuse bladder bleeding from any cause; in adult cancer survivors the usual causes are pelvic radiation and, less often, oxazaphosphorine chemotherapy or BK polyomavirus after hematopoietic stem cell transplantation.[1][2] Late radiation cystitis has been reported in up to 10% of patients who receive pelvic radiotherapy, can present months to decades after treatment, and ranges from microscopic hematuria to transfusion-dependent bleeding and an end-stage, contracted bladder.[3][4]

For the reconstructive surgeon, the condition matters at two points. The first is acute bleeding that fails catheter-based care and needs escalation through intravesical, hyperbaric, interventional and surgical options. The second is the end-stage irradiated bladder, where the decision is between continued bladder salvage and urinary diversion with or without cystectomy.[1][5] Tissue biology after radiation, and hyperbaric oxygen physiology, are covered in Radiation and Tissue Effects and Hyperbaric Oxygen Therapy.

Definition and Grading​

Radiation cystitis is divided into acute cystitis during or shortly after treatment, which is usually self-limited, and late cystitis, which conventionally begins more than 90 days after radiotherapy.[3][6] Late toxicity is graded by clinician-reported scales. RTOG/EORTC and CTCAE grades are not interchangeable, and a trial's "grade ≥2 GU toxicity" is a composite endpoint that includes frequency, dysuria, obstruction and incontinence as well as hematuria.[6][7]

GradeRTOG/EORTC late bladder morbidity[6]CTCAE v5.0, cystitis noninfective[7]
1Slight epithelial atrophy, minor telangiectasia, microscopic hematuriaMicroscopic hematuria; minimal increase in frequency, urgency, dysuria or nocturia
2Moderate frequency, generalized telangiectasia, intermittent macroscopic hematuriaModerate hematuria; catheter or bladder irrigation indicated; limits instrumental activities of daily living
3Severe frequency and dysuria, severe generalized telangiectasia (often with petechiae), frequent hematuria, capacity <150 mLGross hematuria; transfusion, IV medication or hospitalization indicated; elective endoscopic, radiologic or operative intervention indicated
4Necrosis, contracted bladder (capacity <100 mL), severe hemorrhagic cystitisLife-threatening consequences; urgent radiologic or operative intervention indicated
5Death from toxicityDeath

The grade guides the intensity of treatment, but it does not replace a description of the actual problem: transfusion requirement, clot retention, number of admissions, bladder capacity, upper-tract status and the patient's symptom burden.[1]

Epidemiology and Latency​

Reported incidence varies with the treatment field, dose, fractionation, concurrent therapy, the definition of cystitis and the length of follow-up. Severe hematuria is less common than any-grade cystitis.[3][4]

Radiation sourceEvidenceInterpretation
Prostate RT, population dataIn a Medicare-linked cohort, radiotherapy was associated with radiation cystitis (HR 131.47, 95% CI 52.48–329.35) and bladder cancer (HR 2.78, 95% CI 1.92–4.02) compared with untreated participants[8]Observational; the very large hazard ratio reflects a near-absent baseline rate in untreated men
Prostate LDR brachytherapy boostIn ASCENDE-RT, five-year cumulative grade 3 GU events were 18.4% after LDR boost and 5.2% after dose-escalated EBRT boost[9]Composite GU events that include more than hemorrhagic cystitis; both arms received pelvic RT and androgen deprivation
Prostate SBRTIn PACE-B (874 men), cumulative late RTOG grade ≥2 GU toxicity through five years was 26.9% after five-fraction SBRT and 18.3% after conventional or moderately hypofractionated RT[10]Composite endpoint; low- and intermediate-risk disease without androgen deprivation
Cervical cancer RTIn 1,784 patients treated with radiotherapy for stage Ib cervical cancer, hemorrhagic cystitis developed in 6.5%, at a mean of 35 months after treatment, with some cases appearing up to 20 years later[11]Older external-beam and brachytherapy techniques; demonstrates continuing risk over two decades
Rectal, endometrial and other pelvic RTIncluded in pooled descriptions of late radiation cystitis after pelvic radiotherapy[3][1]Site-specific hemorrhagic cystitis rates are poorly defined; the bladder dose and volume matter more than the primary tumor

Latency is long. Bleeding typically appears months to years after treatment, and the cervical cancer data show new events beyond 10 years.[11][4] In a Mayo Clinic series of cystectomy for refractory hemorrhagic cystitis, 17 of 21 patients had prior prostate radiotherapy, and the median interval from radiation to cystectomy was 91 months.[12] AUA/ASTRO/SUO guidance on salvage radiotherapy after prostatectomy identifies late hemorrhagic cystitis as a potential harm to be discussed when salvage treatment is considered.[13]

Pathophysiology​

Radiation injures the urothelium, the microvasculature and the detrusor. The late lesion is progressive obliterative endarteritis with ischemia and tissue hypoxia, followed by submucosal and detrusor fibrosis. Fragile neovascular telangiectasias in the hypoxic mucosa bleed with minimal trauma, and fibrosis reduces capacity and compliance.[14][15] The changes vary within the treatment field.[15] Bleeding may come from discrete sites amenable to fulguration or from diffuse oozing across the bladder.[4] Hyperbaric oxygen is used to treat this hypoxic, hypovascular state.[16]

See Radiation and Tissue Effects for the broader tissue biology and its implications for grafts, flaps and anastomoses.

Non-Radiation Hemorrhagic Cystitis in Survivors​

CauseMechanism and settingPrevention and specific management
Cyclophosphamide and ifosfamideUrotoxic metabolite acrolein injures the urothelium; bleeding can occur during treatment or later[2][17]ASCO protectant guidance supports mesna to reduce ifosfamide urothelial toxicity, and mesna or forced saline diuresis with high-dose cyclophosphamide; established hemorrhagic cystitis is managed with the same bladder-directed ladder as radiation cystitis[17][2]
BK polyomavirus after allogeneic HSCTReported in 7–54% of adult allogeneic HSCT recipients; diagnosis requires cystitis, macroscopic hematuria and high urinary BK viral load, with other causes excluded[18]Supportive care, hydration, catheter drainage and irrigation; evidence for antiviral therapy is limited; refractory cases may need the interventional options below[18]

These patients differ from radiation survivors. Thrombocytopenia, graft-versus-host disease, immunosuppression and concurrent infection change both the bleeding risk and the risk of intervention, and treatment is coordinated with the transplant or oncology team.[18][2]

Evaluation​

Hematuria in an irradiated patient is not assumed to be radiation cystitis. Neither the radiation history nor bacteriuria establishes the diagnosis, and recurrent or new malignancy must be excluded.[1] Radiotherapy for prostate cancer is associated with later bladder cancer, which adds to this concern.[8]

  • Hemodynamic status and bleeding severity. Clots, retention, hemoglobin trend and transfusion requirement.[1][4]
  • Coagulation and medications. Platelet count, coagulation studies, renal function, and review of anticoagulant and antiplatelet therapy with the prescribing team; anticoagulation does not explain away hematuria.[1]
  • Urine studies. Culture to treat concurrent infection; cytology as indicated.[1]
  • Upper-tract imaging. CT urography or an equivalent study to exclude an upper-tract source and obstruction, preferably before antifibrinolytic therapy.[1][19]
  • Cystoscopy. Clot evacuation, identification of discrete bleeding sites or diffuse oozing, assessment of capacity, and biopsy of any lesion concerning for malignancy.[1][4]
  • Fistula and necrosis. Cystography or cross-sectional imaging when necrosis, perforation, fistula or osteitis is suspected; these findings change management and usually exclude formalin.[1][20]

Stepwise Management​

Management depends on bleeding severity, bladder capacity, renal function, comorbidity and local expertise. The CUA best practice report separates initial care, persistent or recurrent bleeding, and refractory life-threatening bleeding; it does not require every patient to pass through each step in order.[1]

StepInterventionMain rolePrincipal cautions
1ResuscitationTransfusion, correction of coagulopathy, review of anticoagulants[1][4]Thromboembolic risk when anticoagulants are stopped is weighed with the prescriber
2Large-bore catheter and clot evacuationBedside or operative clot evacuation; a large three-way catheter for drainage[4]Retained clot sustains bleeding and obstruction
3Continuous bladder irrigation (CBI)Saline irrigation after clot clearance[4][1]Recurrent clot retention
4Cystoscopic fulgurationTreats discrete bleeding sites at the same anesthetic as clot evacuation[1][4]Less useful for diffuse oozing
5Intravesical alumPersistent bleeding after CBI; no anesthesia required[21][1]Aluminum absorption, especially with renal impairment; bladder spasm; transient delirium
6Intravesical hyaluronic acid or chondroitin sulfatePersistent mild-to-moderate bleeding and symptoms; possible relapse prevention[22][23]Slow onset; limited evidence in severe acute bleeding
7Hyperbaric oxygen therapy (HBOT)Persistent or recurrent radiation cystitis in a stable patient[24][25]30–40 sessions; access; does not provide emergency hemostasis
8Aminocaproic acidOral or intravesical antifibrinolytic in selected cases[19]Exclude upper-tract bleeding; hard clots form if bladder clot is not cleared; thrombotic events
9Tranexamic acidOff-label antifibrinolytic adjunct[26]Upper-tract clot obstruction; thrombotic risk
10Intravesical formalinRefractory bleeding after less invasive treatment fails[1][20]General or regional anesthesia; exclude VUR and perforation; fibrosis, contracture and upper-tract injury
11Selective internal iliac or superselective vesical artery embolizationRefractory or life-threatening bleeding, especially in patients unfit for surgery[27][28]Recurrent bleeding; repeat procedures; periprocedural deaths reflect comorbidity
12Bilateral nephrostomy diversionDiverts urine from the bladder when bleeding persists[29]Long-term tubes; the defunctionalized bladder remains in situ
13Cystectomy and urinary diversionRefractory bleeding, end-stage bladder, fistula, intractable pain[12][5]High morbidity and mortality in this population

Resuscitation, clot evacuation and irrigation​

Most episodes of radiation hemorrhagic cystitis respond to clot evacuation, catheter drainage and irrigation, with correction of coagulopathy.[4][1] A large-caliber three-way catheter allows irrigation, but a bladder full of organized clot usually needs evacuation under anesthesia with a rigid sheath and an Ellik evacuator; cystoscopic fulguration of discrete bleeding points can be done at the same time.[4] See Three-Way Catheter and Ellik Evacuator.

Intravesical alum​

Alum (aluminum potassium or ammonium sulfate) is an astringent that precipitates protein at the bleeding surface. It is given by continuous irrigation and does not require anesthesia.[1][19] In a Mayo Clinic series of 40 patients who had failed saline irrigation and clot evacuation, alum resolved hemorrhagic cystitis in approximately 60% and produced a durable response in approximately one third. Adverse events occurred in 15 of 40 (38%): bladder spasm in 14, transient delirium in 2 and urinary tract infection in 2; one patient had an asymptomatic rise in blood aluminum that normalized.[21] Aluminum levels and mental status are monitored during treatment, particularly with impaired renal function.[1][21]

Intravesical glycosaminoglycan replacement​

Hyaluronic acid with or without chondroitin sulfate is intended to restore the urothelial glycosaminoglycan layer. In a small randomized trial, intravesical hyaluronic acid and HBOT produced similar sustained reduction in bleeding, pelvic pain and frequency over at least 12 months.[22] Retrospective data suggest a role in preventing relapse of hematuria, but evidence is limited and onset is slower than with alum or formalin.[23][1]

Hyperbaric oxygen therapy​

HBOT has the best randomized evidence of any treatment for chronic radiation cystitis. RICH-ART randomized 87 patients and analyzed 79; at 6–8 months the improvement in EPIC urinary total score was 10.1 points greater with HBOT than with standard care (95% CI 2.2–18.1). The trial excluded patients with recent bleeding requiring more than 500 mL of transfusion in four weeks, a permanent catheter, bladder capacity below 100 mL and bladder fistula.[24] In the five-year report, after control patients had been offered HBOT, the modeled improvement in EPIC urinary score among 70 HBOT-treated patients was 19.1 points (95% CI 13.3–24.9); only 39 had five-year observations, and 9 of 70 received additional HBOT for recurrence.[30] This supports durability in some patients but is not a five-year randomized comparison.

For hematuria specifically, a 2024 meta-analysis of 14 studies and 556 patients estimated complete remission in 55% (95% CI 51–59%) with heterogeneous evidence.[25] A retrospective series of 60 patients associated HBOT started within six months of hematuria onset with higher response rates.[31] The 2023 Cochrane review rated the evidence for late radiation injury of the bladder as low to moderate certainty and found mainly mild adverse events, such as barotrauma and transient myopia.[16] Regimens, contraindications and logistics are on the Hyperbaric Oxygen Therapy page.

Antifibrinolytics: aminocaproic acid and tranexamic acid​

Aminocaproic acid inhibits plasminogen activation and can be given orally or intravesically. Small series report high response rates, without data on durability. Upper-tract bleeding is excluded first, because stabilized clot can obstruct the ureter, and bladder clot is evacuated completely before treatment, because aminocaproic acid can produce hard clots that are difficult to remove. Thrombotic complications, myopathy and rhabdomyolysis have been reported, mostly with oral use.[19]

Tranexamic acid has been studied off-label for hematuria. A systematic review of seven heterogeneous studies (970 participants) reported reductions in bleeding, but effects on transfusion were variable and the review does not establish a regimen for radiation cystitis.[26] The same upper-tract clot precautions apply; see Tranexamic Acid.

Intravesical formalin​

Formalin fixes the bladder mucosa and occludes telangiectatic vessels. It is reserved for bleeding that has failed less invasive treatment because of its morbidity.[1][4] Instillation is painful and is performed under general or regional anesthesia. A cystogram is obtained first to exclude perforation and vesicoureteral reflux, because formalin reaching the upper tracts or the peritoneum causes serious injury; reported complications include bladder fibrosis and contracture, ureteral obstruction and fistula.[4][1]

In a 1989 analysis of 235 previously reported cases, complete response rates were 71% with 1% formalin, 78% with 5% and 83% with 10%; the difference was not statistically significant.[32] In a contemporary cohort of 8 patients with radiation cystitis treated with 1–4% formalin, 6 (75%) responded, with a median time to resolution of 4 days; intraoperative cystography showed reflux in 4 (50%). Of the 6 responders, 2 later needed cystectomy, one for recurrent hematuria and one for bladder neck contracture and bladder dysfunction.[20] The high prevalence of reflux in that series supports routine cystography before every instillation.

Selective embolization​

Angiographic embolization of the anterior division of the internal iliac artery, or superselective embolization of the vesical arteries, is used for refractory or life-threatening bleeding, particularly in patients who are unfit for major surgery.[28][1] A systematic review of 295 patients described selective embolization as a safe and effective way to control intractable bladder hemorrhage.[28] In a series of 20 patients with bladder or prostate bleeding, embolization was technically successful in 18 (90%) and controlled bleeding after the first procedure in 15 of 18; 4 of 14 survivors had late recurrence, and the 20% periprocedural mortality was attributed to underlying disease.[27] In 9 patients with hemorrhagic cystitis, superselective vesical artery embolization stopped hematuria within 48 hours in all.[33] These are small retrospective series with selected patients.

Nephrostomy diversion​

Bilateral percutaneous nephrostomy diverts urine away from the bladder. In a retrospective series of 24 patients with refractory hemorrhagic cystitis, hematuria resolved in 17 (71%), with a median time to resolution of 12 days, and the median severity grade fell from 3 to 1.[29] Nephrostomy can serve a patient too unwell for cystectomy, but it leaves the bladder in situ, with the retained-bladder risks described below.[1][34] See Nephrostomy Tube.

Cystectomy and urinary diversion​

Cystectomy with urinary diversion is the definitive treatment for refractory bleeding, a contracted end-stage bladder, fistula or intractable pain.[1][5] The patients are typically older and comorbid, and the field is irradiated. In the Mayo Clinic series of 21 patients, all of whom had failed clot evacuation, fulguration and irrigation, 42% had Clavien grade III–V complications and 90-day mortality was 16%.[12] In a nine-center study of 100 men who underwent urinary diversion for urinary adverse events of prostate radiation, short- and long-term complication rates were considerable.[35] Among 34 women diverted for late effects of gynecologic radiotherapy, 79.4% had a complication within 90 days and 26.5% a high-grade complication; rates did not differ significantly by diversion type or concurrent cystectomy in this small cohort.[36]

Patient-reported benefit has been described. In a prospective cohort of 55 patients diverted for radiation-related injury, 47 with paired surveys reported improved global health, pain and quality of life, with low decision regret, over a median follow-up of 47.7 months; there was no comparison group.[37]

Operative planning in the radiated field accounts for dense pelvic fibrosis, obliterated tissue planes around the bladder, rectum and vagina, and the location of irradiated bowel when a segment for diversion is chosen.[5] See Simple Cystectomy and Urinary Diversion.

Evidence Summary​

TreatmentBest available evidenceReported resultLimitation
HBOTRICH-ART RCT, n = 79 analyzed[24]EPIC urinary score +10.1 points over standard care at 6–8 monthsOpen-label; symptom endpoint; excluded severe bleeding, capacity <100 mL and fistula
HBOT, long termRICH-ART follow-up, n = 70[30]Modeled +19.1 points at 5 years; 9/70 retreatedSingle-group follow-up; 31/70 missing at 5 years
HBOT, hematuriaMeta-analysis, 14 studies, n = 556[25]Complete remission 55% (95% CI 51–59%)Heterogeneous, mostly observational
Hyaluronic acidSmall RCT against HBOT[22]Similar sustained reduction in bleeding over at least 12 monthsSmall sample; not powered for equivalence
AlumRetrospective series, n = 40[21]Resolution approximately 60%; durable approximately one thirdSingle center; selected patients
FormalinPooled case analysis, n = 235; cohort, n = 8[32][20]Complete response 71–83%; 6/8 respondersHistorical and small series; morbidity underreported
Tranexamic acidSystematic review, 7 studies, n = 970[26]Reduced bleeding; variable transfusion effectMixed etiologies; not specific to radiation
EmbolizationSystematic review, n = 295; series[28][27]Initial control in most; late recurrence in 4/14 survivors in one seriesRetrospective; heterogeneous techniques
NephrostomyRetrospective series, n = 24[29]Resolution in 17/24 (71%)Single center; mixed etiologies
CystectomyRetrospective series, n = 21[12]Clavien III–V 42%; 90-day mortality 16%Single center; reflects a frail population

The Contracted Radiated Bladder and Reconstructive Endpoints​

A grade 4 radiation bladder has a small capacity, poor compliance and often coexisting outlet stenosis, incontinence, fistula or pain. Bladder salvage by repeated hemostatic procedures does not restore capacity.[6][5]

Augmentation cystoplasty has a limited role. It leaves the irradiated bladder remnant and outlet in place. A review of the end-stage irradiated bladder discusses augmentation as an organ-preserving option but concludes that cystectomy with urinary diversion is a safe and viable option in selected irradiated patients, with the goal of improving quality of life.[5] Augmentation in a radiated bladder is therefore an individual decision made with knowledge of outlet function and the patient's ability to catheterize; see Bladder Augmentation.

Diversion type. Most diversions for radiation injury are noncontinent; in the gynecologic radiotherapy cohort, 26 of 34 women (76.5%) received a noncontinent diversion.[36] In the multi-institutional prostate radiation series, diversions were urinary conduits or continent catheterizable pouches.[35]

Bladder in situ or cystectomy. Supravesical diversion without cystectomy shortens the operation but leaves a defunctionalized bladder that can bleed, become infected or develop pyocystis. In a series of 30 patients diverted for benign disease with the bladder left in situ, 80% had at least one complication related to the bladder (67% pyocystis), 43% were rehospitalized and 30% needed reoperation, including cystectomy in 4.[34] In a second series of 24 patients, whose indications included radiation and hemorrhagic cystitis, 54% had complications of the retained bladder, 33% had pyocystis and 25% later needed cystectomy.[38] Both groups favored primary cystectomy when undiversion is not anticipated. This morbidity is weighed against the added operative risk of concurrent cystectomy in a frail, irradiated patient.[12][36]

Counseling and Follow-Up​

  • Natural history. Bleeding can recur years after a successful treatment; treatment response after alum, formalin, HBOT and embolization is often incomplete or temporary.[21][30][27]
  • Timing of HBOT. Earlier referral after hematuria onset is associated with better response, and HBOT requires daily sessions over several weeks.[31][24]
  • Formalin consent. Counsel about anesthesia, bladder contracture, upper-tract injury and the possibility of later cystectomy.[20][4]
  • Diversion consent. Discuss high complication and readmission rates, the expected stoma or catheterization burden, and whether the bladder will be removed.[12][36][35] Pain relief and freedom from bleeding may be the main goals even when continence cannot be restored.[37]
  • New hematuria. Repeat evaluation for malignancy and upper-tract disease rather than attributing every episode to radiation.[1][8]
  • Salvage radiotherapy. Before salvage RT after prostatectomy, late hemorrhagic cystitis is included in counseling about urinary harms.[13]

See Also​

References​

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2. Li KD, Jones CP, Hakam N, et al. "Haemorrhagic cystitis: a review of management strategies and emerging treatments." BJU Int. 2023;132(6):631-637. doi:10.1111/bju.16140

3. Smit SG, Heyns CF. "Management of radiation cystitis." Nat Rev Urol. 2010;7(4):206-214. doi:10.1038/nrurol.2010.23

4. Pascoe C, Duncan C, Lamb BW, et al. "Current management of radiation cystitis: a review and practical guide to clinical management." BJU Int. 2019;123(4):585-594. doi:10.1111/bju.14516

5. Moring N, Barrett S, Peterson AC, Inouye BM. "Pelvic extirpative surgery for the 'end-stage irradiated bladder'." Cancers (Basel). 2023;15(17):4238. doi:10.3390/cancers15174238

6. Cox JD, Stetz J, Pajak TF. "Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)." Int J Radiat Oncol Biol Phys. 1995;31(5):1341-1346. doi:10.1016/0360-3016(95)00060-C

7. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. US Department of Health and Human Services; 2017. CTEP

8. Unger JM, Till C, Tangen CM, et al. "Long-term adverse effects and complications after prostate cancer treatment." JAMA Oncol. 2024;10(12):1654-1662. doi:10.1001/jamaoncol.2024.4397

9. Rodda S, Tyldesley S, Morris WJ, et al. "ASCENDE-RT: an analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer." Int J Radiat Oncol Biol Phys. 2017;98:286-295. doi:10.1016/j.ijrobp.2017.01.008

10. van As N, Griffin C, Tree A, et al. "Phase 3 trial of stereotactic body radiotherapy in localized prostate cancer." N Engl J Med. 2024;391:1413-1425. doi:10.1056/NEJMoa2403365

11. Levenback C, Eifel PJ, Burke TW, Morris M, Gershenson DM. "Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix." Gynecol Oncol. 1994;55(2):206-210. PMID 7959285

12. Linder BJ, Tarrell RF, Boorjian SA. "Cystectomy for refractory hemorrhagic cystitis: contemporary etiology, presentation and outcomes." J Urol. 2014;192(6):1687-1692. doi:10.1016/j.juro.2014.06.030

13. Morgan TM, Boorjian SA, Buyyounouski MK, et al. "Salvage therapy for prostate cancer: AUA/ASTRO/SUO guideline part I: introduction and treatment decision-making at the time of suspected biochemical recurrence after radical prostatectomy." J Urol. 2024;211(4):509-517. doi:10.1097/JU.0000000000003892

14. Marks LB, Carroll PR, Dugan TC, Anscher MS. "The response of the urinary bladder, urethra, and ureter to radiation and chemotherapy." Int J Radiat Oncol Biol Phys. 1995;31(5):1257-1280. doi:10.1016/0360-3016(94)00431-J

15. Citrin DE, Timmerman RD. "Effects of radiotherapy in normal tissue." N Engl J Med. 2026;394(10):996-1009. doi:10.1056/NEJMra2506017

16. Lin ZC, Bennett MH, Hawkins GC, et al. "Hyperbaric oxygen therapy for late radiation tissue injury." Cochrane Database Syst Rev. 2023;8:CD005005. doi:10.1002/14651858.CD005005.pub5

17. Hensley ML, Hagerty KL, Kewalramani T, et al. "American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants." J Clin Oncol. 2009;27(1):127-145. doi:10.1200/JCO.2008.17.2627

18. Cesaro S, Dalianis T, Hanssen Rinaldo C, et al. "ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients." J Antimicrob Chemother. 2018;73(1):12-21. doi:10.1093/jac/dkx324

19. Jefferson FA, Linder BJ. "Hemorrhagic cystitis: making rapid and shrewd clinical and surgical decisions for improving patient outcomes." Res Rep Urol. 2023;15:291-303. doi:10.2147/RRU.S320684

20. 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-E82. doi:10.5489/cuaj.4047

21. 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):1144-1149. PMC5117970

22. Shao Y, Lu G, Shen Z. "Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis." BJU Int. 2012;109(5):691-694. doi:10.1111/j.1464-410X.2011.10550.x

23. Sanguedolce F, Meneghetti I, Bevilacqua G, et al. "Intravesical instillation with glycosaminoglycan replacement treatment in patients suffering radiation-induced haemorrhagic cystitis: when and which patients can benefit most from it?" Urol Oncol. 2022;40(7):344.e19-344.e25. doi:10.1016/j.urolonc.2022.02.013

24. Oscarsson N, Müller B, Rosén A, et al. "Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial." Lancet Oncol. 2019;20(11):1602-1614. doi:10.1016/S1470-2045(19)30494-2

25. Yang TK, Wang YJ, Li HJ, et al. "Efficacy and safety of hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis: a systematic review and meta-analysis." J Clin Med. 2024;13(16):4724. doi:10.3390/jcm13164724

26. Naseralallah L, Nasrallah D, Alsheikh R, Assami D, Boudaka R. "Tranexamic acid for the management of hematuria: a systematic review." Urology. 2026;210:136-142. doi:10.1016/j.urology.2025.12.035

27. Delgal A, Cercueil J, Koutlidis N, et al. "Outcome of transcatheter arterial embolization for bladder and prostate hemorrhage." J Urol. 2010;183(5):1947-1953. doi:10.1016/j.juro.2010.01.003

28. Taha DE, Shokeir AA, Aboumarzouk OM. "Selective embolisation for intractable bladder haemorrhages: a systematic review of the literature." Arab J Urol. 2018;16(2):197-205. doi:10.1016/j.aju.2018.01.004

29. Farhan A, Lyons GR. "Clinical outcomes following percutaneous urinary diversion for hemorrhagic cystitis." J Vasc Interv Radiol. 2022;33(7):841-844. PMID 35777893

30. Oscarsson N, Rosén A, Müller B, et al. "Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): long-term follow-up of a randomised controlled, phase 2-3 trial." EClinicalMedicine. 2025;83:103214. doi:10.1016/j.eclinm.2025.103214

31. Chong KT, Hampson NB, Corman JM. "Early hyperbaric oxygen therapy improves outcome for radiation-induced hemorrhagic cystitis." Urology. 2005;65(4):649-653. PMID 15833500

32. Donahue LA, Frank IN. "Intravesical formalin for hemorrhagic cystitis: analysis of therapy." J Urol. 1989;141(4):809-812. doi:10.1016/S0022-5347(17)41016-0

33. Mohan S, Kumar S, Dubey D, et al. "Superselective vesical artery embolization in the management of intractable hematuria secondary to hemorrhagic cystitis." World J Urol. 2019;37(10):2175-2182. doi:10.1007/s00345-018-2604-0

34. Eigner EB, Freiha FS. "The fate of the remaining bladder following supravesical diversion." J Urol. 1990;144(1):31-33. doi:10.1016/S0022-5347(17)39358-8

35. Bassett MR, Santiago-Lastra Y, Stoffel JT, et al. "Urinary diversion for severe urinary adverse events of prostate radiation: results from a multi-institutional study." J Urol. 2017;197(3 Pt 1):744-750. doi:10.1016/j.juro.2016.10.091

36. Smith D, Albersheim J, Moses R, et al. "Outcomes of urinary diversion for late adverse effects of gynecologic radiotherapy." Urology. 2020;144:214-219. doi:10.1016/j.urology.2020.06.040

37. Woodle T, Kurtzman JT, Ramsay J, McCormick B, Myers JB. "A prospective analysis of patient-reported health-related quality of life outcomes following urinary diversion for pelvic radiation-related injury." Urology. 2026;214:105-110. doi:10.1016/j.urology.2026.01.017

38. Fazili T, Bhat TR, Masood S, Palmer JH, Mufti GR. "Fate of the leftover bladder after supravesical urinary diversion for benign disease." J Urol. 2006;176(2):620-621. doi:10.1016/j.juro.2006.03.056