Page 3 - CUA Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis

BPR: Radiation-induced hemorrhagic cystitis

diffuse erythema, telangiectasia with or without ulcerations formation. Individual case studies have reported a risk of
can help confirm the diagnosis of RHC. At the time of cystos- aluminum toxicity in individuals in renal failure. 23
copy, fulguration of suspected vascular lesions may provide The most recent, and largest case series reported the use
control of hematuria. In a case series assessing the effective- of alum irrigation in 40 patients (38 of whom had previous
ness of cystoscopy and fulguration for hematuria control radiation treatment) with symptoms of hemorrhagic cysti-
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in patients with either radiation- or chemotherapy-induced tis; 60% of these patients demonstrated an improvement
symptoms, 61% (20/33) of patients achieved resolution of in their symptoms and required no further treatment prior
14
symptoms after initial endoscopic treatment. Only 36% to discharge. The treatment was well-tolerated and 90% of
(4/11) of patients who had refractory symptoms responded patients were able to receive their treatment as prescribed.
to a second cystoscopy and fulguration. Two patients discontinued due to inability to tolerate bladder
Multiple small case series have assessed alternatives to spasms and two for altered level of consciousness. Overall,
fulguration with Greenlight laser, KTP laser treatment, and 35% of patients experienced bladder spasms. Asymptomatic
argon beam coagulator. 15-17 All series report laser therapy elevation in serum aluminum was detected in one patient
being well-tolerated and having a beneficial effect. In the that resolved on discontinuation of the treatment. At a medi-
future, they may play a larger role in the treatment of RHC; an followup of 16.5 months, only 32% of patients required
however, until larger studies can confirm their safety and no further treatment, bringing the durability of this treatment
effectiveness, they remain experimental in nature. Additional into question.
studies have investigated intravesical hemostatic gelatin Recommendation: Irrigation with alum is a practical
matrix (Floseal) in six patients and was noted to be ben- and easily applied treatment for RHC with a comparative-
eficial. 15-17 Fibrin glue has been trialed in the treatment of ly acute onset of action that is generally well-tolerated.
post-hematological stem cell transplant patients and found Special caution should be used in patients with poor renal
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to reduce hematuria, but it has yet to be investigated in the function (Grade 3C).
RHC population beyond individual case studies. 19
Recommendation: All patients with hematuria should Hyaluronic acid
undergo at least one initial cystoscopy with or without Hyaluronic acid (HA) is a mucopolysaccharide whose thera-
fulguration of suspect lesions and biopsy of any lesions peutic benefit is believed to be mediated by the repair of
concerning for malignancy for diagnostic and therapeutic the normal glycoaminoglycan layer of the bladder when
purposes (Grade 3C). Laser therapy and endoscopic use of applied as intravesical installations. It has been shown that
hemostatic agents may play a role in early management of radiation leads to defects in this protective layer, leading to
RHC, but insufficient data exists to evaluate their efficacy chronic inflammatory changes and delayed or prevented
and safety; long-term followup is needed prior to any rec- healing of urothelial cells. Its use as an intravesical agent
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ommendations being made (Grade 3D). is well-studied in the treatment of interstitial cystitis and
painful bladder syndrome, where it was recently recom-
Persistent or recurrent clinically significant hematuria mended as a treatment option in the Canadian Urological
Association guideline. 26
One of the few randomized trials comparing treatment
Intravesical agents modalities for RHC randomized 36 patients to either intra-
vesical therapy with HA or treatment with hyperbaric oxygen
Alum irrigation therapy (HBOT). In the HA group, patients received intra-
27
Intravesical aluminous salts act as an astringent agent and vesical therapy once weekly for one month and then month-
exert their effect through protein precipitation causing ly for two months. Patients in the HBOT group received
decreased capillary permeability, contraction of intercel- daily treatments for 30 treatments. Followup assessment of
lular space, vasoconstriction, and hardening of the capillary symptoms were done at six, 12, and 18 months following
20
endothelium. It is typically administered as a 1% concen- therapy. Complete resolution of hematuria was noted in
tration of alum mixed with sterile water, irrigated through 88%, 75%, and 50% of HA patients at those intervals and
the bladder at 250‒300 ml per hour, at a duration up to the in 75%, 50%, and 45% of patients in the HBOT group. The
discretion of the observing clinician. Ideally, the bladder difference was not statistically significant at any interval and
should be irrigated free of clots prior to initiation of therapy. the author concluded the HA therapy was at least as effective
Historical case series have demonstrated the efficacy and as HBOT in the treatment of hematuria.
tolerability of intravesical alum for a wide range of etiologies A prospective, observational study of 20 patients undergo-
and presentations of intractable bladder hemorrhages. 21,22 ing treatment with intravesical HA compared grading of radia-
The common side effects are bladder spasms, suprapubic tion cystitis, including hematuria, as per EORTC/ROTG clas-
discomfort, and clotting of the catheter due to precipitant sification (scale 1‒5) before treatment and again three months

CUAJ • February 2019 • Volume 13, Issue 2 17