Page 5 - CUA Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis

BPR: Radiation-induced hemorrhagic cystitis

Recommendation: Several case series have shown a discriminate between blood loss from bladder or prostatic
potential reduction of hematuria with treatment with SPP origins. In a case series of 44 patients looking at the role
in patients with RHC. It is safe and generally well-tolerated, of TAE in the management of intractable hematuria hem-
however, the slow onset of action may limit its usefulness orrhage of oncological origin, Liguori et al found that the
in treatment of acute or severe RHC (Grade 3C). majority of patients (82%) experienced an initial resolution
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of hematuria. The ability to perform selective and super-
Experimental options selective TAE has reduced the risk of ischemic-related side
WF10, an intravenously administered macrophage regulator, effects. Historical studies have demonstrated ischemic-medi-
has shown promising results for treatment and decreased ated side effects in as high as 65% in patients undergoing
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recurrence of RCH in two studies published at a single cen- internal iliac artery embolization. Although most of these
tre, 43,44 but is not commercially available in Canada. are transient post-embolization syndrome, they also include
Two small case studies explored the use of estrogen in more serious complications, such as bladder necrosis and, in
treatment of hemorrhagic cystitis of multiple etiologies. 45,46 rare cases, Brown-Sequard syndrome. Comparable modern
While both showed reduction in hematuria, larger studies series published in the last decade quote minor and self-
are needed before recommendations regarding effectiveness resolving complication rates from 9‒31%, with a technical
or safety can be made. success rate of 88‒100%. 54,55
There is conflicting evidence that may point to a role for Recommendation: TAE is a viable option for control of
cranberry juice in preventing acute urinary symptoms in RHC in those for whom less invasive methods have been
patients undergoing pelvic radiation; however, there is no data unsuccessful. Preference should be given to selective or
to suggest it has a role in management of late-effect RHC. 47-49 super-selective embolization when available to lessen pos-
There is a growing body of evidence exploring the use sible side effects (Grade 3C).
of tranexamic acid in the control of hemorrhage of mul -
tiple etiologies. Its use has previously been suggested in the Formalin
management of RHC. A randomized control trial recently
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assessed the use of intravenous tranexamic acid in control- Intravesical formalin was first described in the treatment of
ling of hematuria of multiple etiologies in the acute setting. It bladder hemorrhage in the late 1960s, and was soon assessed
found a decreased time on CBI until resolution of hematuria; in a RHC cohort. The proposed mechanism involved capil-
however, no significant difference in blood loss or transfu- lary occlusion and protein fixation at the urothelium level. 56
sions rates were noticed in the treatment group. While Due to pain with administration, it must administered in
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further studies may demonstrate a benefit in treatment of an operating room setting with either a general or spinal
patients with RHC with tranexamic acid, at this time there anesthetic. While its rapid onset of action is appealing, its
is insufficient published data to support this. use is somewhat controversial because of its high morbid-
Recommendation: Multiple systemic agents have been ity, which appears to be proportional to the concentration
used in small experimental situations for treatment of RHC. of formalin used. 3
Until further studies are completed, no formal recommen- The largest review of the efficacy of formalin instillation
dations can be made regarding their use (Grade 3D). to treat hemorrhagic cystitis of multiple etiologies was a
systematic review of retrospective case series published in
Refractory and life-threatening hematuria 1989. The article included 235 patients stratified into three
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groups by the concentration of formalin instilled (10% vs.
3‒6% vs. 1‒2%). The complete response rates were 88%,
Transarterial embolization 78%, and 71%, respectively. One benefit of formalin instil-
lations was that complete response was typically achieved
Advances in interventional radiology have allowed for accu- within 48 hours of a single instillation. Major complications
rate selective and super-selective transarterial embolizations were typically associated with refluxing into the upper uri-
(TAE) that provide clinicians with management alternatives nary tract and consisted of ureteric stricture function, ure-
to more radical surgical procedures in patients with persistent teropelvic junction and uretrovesical junction obstruction
or life-threatening hematuria. The benefit of TAE is its safety requiring urinary diversion, decreased bladder capacity, and
and tolerability in comparison to more aggressive surgical vesicular fistulas. The mortality rates for 10% and 4‒6% for-
procedures in the frail and elderly patients, who make up a malin instillation were recorded at 5.7% and 2.2%, respec-
significant proportion of patients with RHC. However, these tively. No mortalities occurred in the 21 patients treated
procedures are not without their own risks and side effects. with 1‒2% concentration.
Unfortunately, many of the studies on TAE for hematuria Several other studies were completed that found formalin
include urological bleeding of multiple etiologies and do not to be associated with a high treatment efficacy, but with

CUAJ • February 2019 • Volume 13, Issue 2 19