Page 4 - CUA Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis

Goucher et al

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after the completion of six scheduled treatments. The mean on resolution of hematuria was recently published. It includ-
radiocystitis scores before and after HA treatment were 2.70 ed one small, randomized control trial, two prospective tri-
34
and 1.45, respectively (p<0.01), with only minor side effects als, and 11 retrospective case series. This meta-analysis
described. It is notable that no patients with grade 4 or 5 represents 602 patients followed for at least one year. Partial
toxicity, considered severe symptoms, were included in this or complete response was noted in 84% of patients (confi-
study. Beyond hematuria, recent prospectively collected data dence interval [CI] 76‒91) in the pooled analysis. The most
suggests that intravesical treatment with HA in combination common complications were barotrauma, frequent barotrau-
with chondroitin sulfate (another glycosamniglycan) produces matic otitis in 6% of participants. Visual field disturbances
a clinically significant improvement in post-radiation LUTS were noted in 1% of participants.
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and bother. In a study published by Gacci et al, 80 patients Select case series offer followup data available for up
with previous radiation therapy and new-onset or worsening to a decade after treatment and seem to suggest that suc-
LUTS symptoms were shown to have a statistically significant cessful treatment with HBOT may offer a durable response
reduction in urgency, frequency, nocturia, and bladder pain, for patients. One study followed 32 of its participants for
as measured by patient-reported outcomes after intravesical an average of 11.6 years and found the resolution rate of
treatment with HA and chondroitin sulfate. macroscopic hematuria to be 81%. A smaller case series
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Recommendation: Intravesical therapy with HA may supported this data, as 12 of 13 participants remained free
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improve symptoms of RHC and may provide further benefit of hematuria at 10 years. Recently, authors have sought to
in those with significant LUTS. Its slow onset of action and describe their experience using HBOT as a primary therapy
lack of research in severe hematuria may limit its usefulness in cases of severe RHC. In one study, 38 patients present-
in the acute or inpatient setting (Grade 3C). ing with grade IV EORTC hematuria requiring transfusions
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received HBOT therapy as first-line monotherapy. After
Other intravesical agents an average of 33 treatments, 87% of patients had complete
Intravesical instillation of the antifibrinolytic agent epsilon resolution of hematuria. Long-term data were not available
aminocaproic acid (EACA) was shown to improve hematuria to assess the durability to of treatment.
in 34 patients in case series of 37 patients with intractable Recommendation: Multiple studies have demonstrated
bladder hemorrhage, most of whom had either radiation- or that HBOT is safe and effective and should be consid -
cyclophosphamide-induced cystitis; however this has not ered an early treatment option for RHC in patients who
been repeated in contemporary studies since its publication in have failed cystoscopy and fulguration. Due to significant
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1992. Intravesical instillations of prostaglandins have been resource and expertise requirements, its use may be limited
demonstrated in several smaller case series to be effective based on access and availability (Grade 3C).
in treating hemorrhagic cystitis secondary to treatment with
cyclophosphamide, but there are no large studies to suggest Sodium pentosan polysulfate
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their effectiveness in RHC. Silver nitrate instillations have Sodium pentosan polysulfate (SPP) is a semisynthetic polyscac-
been tried and were found to be ineffective in limiting RHC. 32 charide formulated as an oral medication that serves as a syn-
Recommendation: Several intravesical options have been thetic glycosaminoglycan. It adheres to the bladder mucosa,
trialed in limited case series, but require replication, etiol- where it supplements the bladder’s own glycosaminoglycan
ogy-specific assessment, or comparative data before they layer in a similar fashion as intravesical treatment with HA. It
can be formally included as recommendations (Grade 3D). has been previously shown to be effective in the treatment of
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interstitial cystitis. The largest study to assess its effectiveness
Systemic agents in hematuria secondary to radiation followed 60 consecutively
enrolled patients who were treated with 100 mg orally of SPP
Hyperbaric oxygen therapy (HBOT) three times daily. In 10 patients, hematuria was noted to have
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Radiation to the bladder causes obliterative endarteritis of resolved completely, and there was partial resolution in 21
blood vessels creating cellular hypoxia, bladder ischemia, patients. However, the applicability of this study was limited
and fibrosis. This may lead to superficial fragile blood vessels by the large number of participants not available for followup
prone to recurrent bleeding. Patients who undergo HBOT or who passed away during the study from causes unrelated to
3
inhale 100% O at pressures of 1.4‒3.0 ATM, allowing for hematuria. Two other small case series have also demonstrated
2
hyperoxygenation of tissue. Hyperoxia induces primary neo- the benefits of oral SPP. 40,41 Its usefulness was noted primarily
vascularization, secondary growth of healthy granulation tis- by its safety, tolerability, and ease of administration; however,
sue, and induces short-term vasoconstriction that may help the onset of action was found to be 1‒8 weeks, limiting its use
control active bleeding. 33 in the acute setting. A recent case series has suggested a risk
HBOT is the most studied treatment option for RHC. A of pigmentary maculopathy associated with long-term chronic
scoping review and meta-analyses evaluating this treatment use of SPP (median duration of 186 months). 42

18 CUAJ • February 2019 • Volume 13, Issue 2