Page 6 - CUA Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis

Goucher et al

potentially severe complications. In a study of 35 patient III or greater complications, including 15% who required
with RHC post-cervical radiation, 89% were found to have a second operation, and death in 4.5% of patients within
complete response after a single instillations; however, the first 90 days. These rates of complications outpace the
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31% had major complications. One contemporary study comparable rates in patients undergoing radical cystectomy
investigated eight patients treated with formalin instillations for bladder cancer. Both authors attributed this to baseline
after less invasive treatments had failed. In this study, each fragility and comorbidities in this patient population exac-
patient had a preoperative cystogram to assess for perfora- erbated with the challenge of operating in a previously
tion or vesicoureteral reflux, and if any reflux was suspected, radiated field.
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Fogarty catheters were used to obstruct the ureter. Formalin Small case studies have evaluated the use of urinary diver-
concentration ranged from 1‒4% and contact time was kept sion alone in those who may not tolerate a cystectomy, either
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to 10‒15 minutes. The complete resolution rate was 75% through cutaneous ureterostomy or bilateral nephrostomy
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and only one patient had major complications necessitat- tubes. Although both studies were quite small, they showed
ing intensive care unit admission. A detailed description of improvement in hematuria using urinary diversion alone;
the procedure can be found within this article for clinicians this may be a beneficial surgical alternative in patients for
unfamiliar with this treatment option. whom cystectomy is not a viable option. Caution should be
Procedural variations for decreasing the morbidity asso- advised, as long-term followup in urinary diversion without
ciated with formalin instillations have been proposed, from cystectomy for benign conditions has shown a high rate of
decreasing formalin concentration to alternative methods complications in the remaining bladder. 66
of formalin delivery. A small, prospective study compared Recommendation: Urinary diversion with or without
intravesical instillation of 4% formalin in 11 patients to cystectomy for RHC should be reserved only for those
endoscopic placement of formalin soaked pledgets. 59 who have failed previously available therapy, and clini-
Success rate was similar (82% and 75%, respectively), cians and patients should be aware of the high morbidity
however the intravesicle instillation group suffered from and mortality of the procedure before proceeding with
four major complications, whereas the pledget group suf- surgery (Grade 3C).
fered only minor side effects. The differences were not
statistically significant and while a comparable method was Discussion
described in two individual case studies, 60,61 followup with
further larger or prospective studies is lacking.
Recommendation: Due to significant morbidity associ- Treatment sequencing
ated with the procedure, formalin instillations should only
be used in those who have failed less invasive treatments. There is a lack of consensus or comparative evidence to
If treatment is necessary, all attempts should be made to suggest superiority of one treatment of RHC over another.
prevent reflux into the upper tracts, and the patient needs The lack of high-quality evidence has limited the ability for
careful monitoring for potential side effects (Grade 3C). previous authors to conclusively state the order that treat-
ment should be provided in the cases of refractory therapy.
Cystectomy and urinary diversion There have been several previous attempts to make recom-
mendations for treatment algorithms, with the general con-
Unfortunately, a small percentage of patients will present sensus that treatments should be offered initially using the
with life-threatening hemorrhagic cystitis that is refractory least invasive approaches and progressing to more invasive
to conservative and non-operative measures. These patients approaches as a general principle. 67-71
can be successfully treated with urinary diversion and cys- This report seeks to provide a logical and stepwise
tectomy, however, the associated morbidity with this proce- approach to the management of radiation cystitis. Given
dure is high. Several case series have examined the use of the wide variety of clinical states that a patient with RHC
cystectomy in patients who had previously failed less inva- may present, a linear treatment algorithm would be insuf-
sive therapies. One series identified 21 patients with hemor- ficient to provide treatment suggestions appropriate for
rhagic cystitis, 17 from radiation therapy, who underwent different patients depending on the acuity and severity of
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cystectomy. In this series, 42% of patients experienced the symptoms. Instead we have divided our treatments into
severe complications (defined as Clavien grade III‒V) and three groups based on severity of clinical presentation and
the 90-day mortality rate was 16%. This study echoes the associated morbidity with treatment options (Fig. 1). The
findings of a larger case series looking at surgical outcomes first box represents initial management and provides sugges-
from men undergoing urinary diversion via cystectomy for tions for investigations and supportive therapy. It is focused
multiple adverse effects of radiation, including hematu - on upfront investigations to rule out other causes that may
ria. In this series, 36% of patients experienced Clavian explain or exacerbate hemorrhagic cystitis. Underlying cor-
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20 CUAJ • February 2019 • Volume 13, Issue 2