Page 5 - 2018 Canadian Urological Association guideline for Peyronie’s disease and congenital penile curvature

guideline: Peyronie’s disease

Committee with the current levels of evidence, as only a Health Canada (HC) have now approved Xiaflex (collagenase
single small study exists (less than 20 patients) (Level 4 evi- clostridium histolyticum) for use in PD. Use of collagenase
dence, Grade 3 recommendation). Martin et al demonstrated for PD was first described by Gelbard in 1982, in which
that topical verapamil fails to infiltrate the TA given the TA’s collagenase was injected into PD plaques removed from
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physical properties. Interestingly, in an earlier double-blind- patients and studied in vitro. In 1985, Gelbard performed
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ed study by Fitch et al, 18 men with PD were randomized the first human trials. Intralesional collagenase injection of
to topical verapamil vs. placebo and at three months, 61% clostridial collagenase has demonstrated true efficacy, with
reported a decrease in penile curvature and 88% reported a significant decrease in penile curvature, plaque size, and
resolution of penile pain. Despite reported improvements an improvement in PD symptom bother scores in multiple
in curvature, objective pre-treatment and post-treatment trials. Two large, multicentre, placebo-controlled, prospec-
curvature measurements were not performed, which limits tive, randomized trials (IMPRESS I & II) 35,36 have identified
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these findings; a better quality randomized design of suf- optimal patients for this technique of intralesional collagenase
ficient size executed to contemporary objective endpoints with modelling to be: stable disease with a curvature greater
is required before a recommendation for verapamil gel as a than 30° and less than 90°; no isolated hourglass deformity
PD treatment can be made. 3 or calcified plaque; and normal erectile function (with or
without the use of medications) (Level 2 evidence, Grade
Intralesional therapies B recommendation). In both trials, men in the CCh group
were shown to exhibit a 34% (-17.0±14.8°) improvement
Intralesional verapamil (ILV) is a widely used local agent in penile curvature, compared to 18% (-9.3±13.6°) in the
for PD treatment in Canada. It is the opinion of this panel placebo group, as well as a significantly decreased PD bother
that select intralesional therapies can be offered as treat- score. While uncommon, reported adverse events included
ment options for PD; local therapeutic approaches for PD significant penile hematomas, injection site pain, and penile
is an appealing prospect, potentially obviating the need and swelling. Corporal rupture, while possible, was extremely
risk of surgical management. Intralesional injection has the rare, but often will necessitate surgical repair. 37-39 Use of this
advantage of rapid and direct local delivery of the active technique in men with hinge defects, ventral curvature, hour-
agent into the target tissue, theoretically without the risk of glass deformities, curvature less than 30° and greater than 90°
systemic side effects, and the potential for achieving high has not been evaluated. 35,36 Modifications and optimization
local concentrations. A thorough review of the existing world of treatment protocols continue, as do studies for patients
literature on this approach unfortunately yields disappoint- outside of the initial inclusion criteria, as they are key for
ing results. 1,3,32 While regulatory approval has been granted determining efficacy across wider PD populations. 1,40,41
TM
to purified clostridial collagenase (Xiaflex ) in some mar-
kets, including Canada (Grade B evidence), most injectable Verapamil
agents used for PD are off-label. A wealth of single-centre
reports with relatively small numbers of subjects and vari- In Canada at present, ILV for local treatment of PD is a com-
able outcome measures are the norm for intralesional therapy monly used agent, with more than two decades of experi-
in PD, making comparison and assessment of true efficacy, ence. The technique and first reports were published in the
best approach, and realistic likelihood of positive outcomes mid-1990s, and demonstrated reduction or stabilization of
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difficult to determine. Among the greatest challenges to the plaque size and improved penile deformity using an every
reader of this literature is the lack of standardized outcome two-week series of injections, with several modifications
measurements, choice of and dose of agent, frequency of to treatment regimens since. While acknowledging that
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delivery, and patient selection criteria to optimize results. there currently exists no perfect animal model of PD, ILV
The Committee believes the use of intralesional therapy injection in PD models has shown histological evidence of
is supported in the literature and clinical experience, and cellular changes of decreased collagen and elastin fibers and
recommends clostridial collagenase as first-line therapy with functional erectile improvement; ILV has been evaluated
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use of verapamil or interferon as a second-line option in in 11 randomized designs, including two RCTs and nine
cases where cost or concern related to adverse events limits observational studies. 1,3,44,45
use of collagenase for the management of PD in Canada Despite great strides having been achieved in our under-
(Level 2 evidence, Grade B recommendation). standing of the mechanism of PD development and defining
the ideal local treatment regimen, many unanswered ques-
Collagenase (Xiaflex ) tions remain. It appears that the injected volume, frequency,
TM
concentration, and duration of the ILV injection protocol
Collagenases are enzymes able to degrade interstitial colla- affects outcome results, with longer treatment periods of con-
gens. Both the U.S Food and Drug Administration (FDA) and centrated ILV in younger men with small plaques but large

CUAJ • May 2018 • Volume 12, Issue 5 E201