International Journal of Urology (2020)
14230
Review Article
Peyronie’s disease: Contemporary evaluation and management
Matthew J Ziegelmann,1,2 Petar Bajic1 and Laurence A Levine1
1
Division of Urology, Rush University Medical Center, Chicago, Illinois, and 2Department of Urology, Mayo Clinic, Rochester,
Minnesota, USA
Abbreviations & Acronyms
AMS = American Medical
Systems
AUA = American Urological
Association
CCH = collagenase
Clostridium histolyticum
CUA = Canadian Urological
Association
ED = erectile dysfunction
EMDA = electromotive drug
administration
ICI = intracavernosal
injection
IFN = interferon
ILI = intralesional injection
IPP = inflatable penile
prosthesis
PD = Peyronie’s disease
PDE5I =
phosphodiesterase 5
inhibitor
PDQ = Peyronie’s Disease
Questionnaire
PTT = penile traction
therapy
SPL = stretched penile
length
SWT = shockwave therapy
TAP = tunica albuginea
plication
VT = vacuum therapy
Correspondence: Laurence A
Levine M.D., Division of
Urology, Rush University
Medical Center, 1725 West
Harrison Street, Suite #352,
Chicago, IL 60612, USA.
Email: drlevine@hotmail.com
Received 19 September 2019;
accepted 27 February 2020.
© 2020 The Japanese Urological Association
doi: 10.1111/iju.
Abstract: Peyronie’s disease is a common yet poorly understood condition
characterized by penile pain, curvature, sexual dysfunction and psychological bother.
Peyronie’s disease represents a penile wound healing disorder, and is thought to arise
from exuberant scarring in response to penile trauma in genetically predisposed men. In
the absence of active treatment, the majority of men experience stable or worsening
symptoms, with few reporting spontaneous resolution in penile curvature or other
deformity. In contrast, penile pain improves or resolves in the majority of men.
Treatment options vary based on symptom severity and stability. Several oral therapies
are commonly prescribed, although to date there are no strong data to support any oral
agents as monotherapy for Peyronie’s disease. Other options including penile traction
therapy and intralesional injections result in modest improvements for many patients,
particularly when used early after symptom onset. Penile straightening through
approaches, such as penile plication and plaque incision or partial excision and grafting,
represent the most rapid and reliable approach to correct penile curvature once the
symptoms have stabilized. Side-effects vary based on the type of surgery carried out,
and include penile shortening, sensation changes and erectile dysfunction in the minority
of men. In patients with drug refractory erectile dysfunction and Peyronie’s disease,
placement of a penile prosthesis will address both issues, and is associated with high
levels of patient satisfaction. The current review provides a practical approach to the
modern evaluation and management of patients presenting with Peyronie’s disease.
Key words: collagenase, grafting, penile curvature, plication, Xiaflex.
Introduction
PD is a wound-healing disorder characterized by penile pain, curvature and sexual dysfunc-
tion. Francois Gigot de la Peyronie first described treatment for “induratio penis plastica” in
1743.1,2 However, the condition today known as PD was described as early as the 13th cen-
tury.3,4 PD represents abnormal healing in response to trauma within the penile tunica albug-
inea.5,6 Despite this, just 20–30% of patients recall preceding trauma, such as mis-thrust
during intercourse.6,7 Peyronie’s “plaque” (scar) results from abnormal extracellular matrix
production through upregulation of myofibroblast activity and tissue inhibitors of matrix met-
alloproteinases, among other mechanisms.8,9 There is a link between personal or family his-
tory of PD and Dupuytren’s contractures, suggesting a genetic predisposition.10,11
PD is broadly differentiated into an acute (“active”) inflammatory phase and a chronic
(“stable”) phase. The former is characterized by variable penile pain and progressive penile
deformity. The latter is characterized by symptom stability and pain improvement/resolution.
To date, there are no firmly agreed upon criteria characterizing the transition to chronic PD.
Many experts consider PD to be stable when present for at least 12 months with 3–6 months
of stability.12 In contrast, severe pain rarely persists beyond the acute phase. Treatment varies
depending on the disease phase.12
PD typically occurs during the fifth to sixth decade of life, but can occur at any age.13
Studies have suggested that PD prevalence might be as high as 9% in the general population,
and higher in patients with diabetes or after radical prostatectomy.14–17 However, Shiraishi
et al. found a much lower prevalence of 0.6% in a Japanese cohort.18 In addition to sexual
dysfunction, PD also has a significant impact on quality of life and psychological well-being
for the man and his partner.19 PD is frequently encountered by urologists in practice, and as a
result of increased awareness and the availability of new treatment options, the number of
men presenting for treatment will likely increase in the coming years. Thus, a general
1
MJ ZIEGELMANN ET AL.

understanding of its evaluation and treatment is mandatory. in the acute or chronic phase, which has important treatment
Herein, we provide a general overview of PD for the practic- implications. There is controversy regarding whether ED predis-
ing urologist. poses to PD or vice versa. Penile buckling or “hinge” effect,
wherein the penis bends on itself at the area of deformity as a
PD: Initial evaluation and adjunctive result of axial pressure, is also common. This might result from
testing ED, but is also seen with severe penile deformity.
The penis should be palpated along its entire length from
The initial evaluation should include a thorough history and the pubis to the glans, identifying areas of thickening or pla-
physical examination.12 If possible, the patient’s sexual part- que. SPL is typically measured from the pubis to coronal sul-
ner should be involved in the conversation.20 Important ele- cus. If symptoms of hypogonadism are present, an early
ments of the history/examination are summarized in Table 1. morning total testosterone is recommended.25 Fasting serum
PD evokes significant psychological burden, and all patients glucose, hemoglobin A1c, complete blood count and lipid
should be queried about their emotional well-being.19 The panel might be considered to identify underlying ED risk fac-
PDQ was developed and validated to assess psychosocial out- tors.26 In those endorsing penile sensitivity or risk factors for
comes with PD that might not be adequately captured with neuropathy (e.g. diabetes), biothesiometry is a useful adjunct
alternative metrics.21 The PDQ includes questions in three to record baseline sensory deficits.27
specific domains: (i) psychological and physical symptoms; If minimal bother is reported, no further evaluation is nec-
(ii) penile pain; and (iii) symptom bother. This should be essary. In contrast, those desiring active treatment must
considered as part of the initial work-up to quantify symptom undergo curvature assessment with ICI of an erectogenic
bother and subsequently assess treatment effect.22 agent.12 Patient-provided photographs are an alternative, but
ED is also seen in up to half of men with PD.23,24 Symptom are associated with significant inter/intra-observer variabil-
onset, progression and stability determine whether the patient is ity.28,29 Penile duplex Doppler ultrasound might be carried
out to assess vascular hemodynamics and the degree of plaque
calcification, which has important treatment implications.30,31
Table 1 Important elements of the history and physical examination in a
man presenting with PD
PD treatment
History Laboratory testing (as indicated)
• Pain (flaccid or erect) • Prostate-specific antigen
Treatment options depend on the degree of bother, sexual
• Curvature • Complete blood count
function limitations and symptom stability. In patients with
• Indentation • Fasting serum glucose or
minimal bother, observation alone is reasonable. Few studies
• Shortening hemoglobin A1c have evaluated the natural history of untreated PD. Separate
• Penile instability (“buckling”) • Lipid profile studies from Gelbard and Mulhall using starkly different
• ED • Total testosterone methodology found similar rates of symptom improvement
• Symptom duration
(~12–13%), stabilization (40–45%) and progression (42–
and/or stability 48%) with observation alone.23,32 Patients should be moni-
• Psychological bother tored for symptom progression, at which time active treat-
ment might be warranted.
Questionnaires Adjunctive testing (as indicated)
Historically, men in the acute phase were recommended
• PDQ Biothesiometry (subject changes
in penile sensation) observation or oral monotherapy for at least 6–12 months.
• International Index of
Formal curvature assessment† However, during the past several decades, a variety of alter-
Erectile Function
• Erection Hardness Score • Curvature assessment with native treatments have been studied for early PD. Specifi-
• Patient Health Questionnaire-9
goniometer cally, PTT and ILI might halt progression and allow for
• Point of maximum curvature improvement in curvature and length.33,34 Early intervention
Physical examination • Penile torsion might also prevent the need for invasive treatment, such as
Penis: • Indentation or hourglass penile straightening, or facilitate a less invasive approach.
• Penile elasticity
deformity Surgical straightening with plication or grafting should only
• SPL (pubis to corona)
• Hinge effect‡ be carried out once the patient has entered the “chronic”
• Presence of “plaque”
Penile duplex Doppler ultrasound
phase to limit the risk for deformity recurrence.35 A caveat to
(scar) – location, length
• Presence of penile plaque this principle is that patients with ED refractory to oral medi-
(tunical thickening)
cations might undergo penile prosthesis placement during the
Testicles/scrotum: • Cavernosal artery vascular
active phase to stabilize the PD and prevent further deformity
• Inguinal – lymphadenopathy, hernia assessment
a Peak systolic velocity
and shortening. In the following section, we will review the
General cardiovascular evaluation
b End diastolic velocity
various treatment options for PD.
c Resistive index
Non-invasive therapy
†Evaluation of the erect penis after administration of erectogenic medica-
tions (alprostadil, phentolamine, papaverine) or vacuum erection device.
Oral agents
‡Penile instability or “buckling” when axial pressure is applied to the erect There is no strong evidence to date that supports the use of
penis.
oral monotherapy for PD. The AUA and CUA guidelines on

2 © 2020 The Japanese Urological Association


PD recommend against oral therapy with vitamin E, tamox-
ifen, omega-3-fatty acids, procarbazine and vitamin E/L-car-
nitine combination.12,36 Non-steroidal anti-inflammatories are
indicated for penile pain, particularly in the early phase.12
Data on other agents, such as para-amino-benzoate, L-argi-
nine/citrulline, pentoxifylline and colchicine, are limited by
suboptimal study methodology.12,36 Despite this, many
experts continue to recommend oral therapy because of the
low cost, minimal side-effects, and potential efficacy sug-
gested by in vitro and animal studies.37,38 Recently, there has
been growing interest in daily PDE5I therapy.39 In vitro and
rat model studies have shown that PDE5Is might actually
decrease PD plaque through alterations in fibroblast activity,
decreased collagen deposition and local apoptosis.40,41
Pentoxifylline, another commonly used agent, acts through
non-selective phosphodiesterase inhibition, and has been sug-
gested to modify PD scarring through its effects on nitric
oxide. Ultimately, multimodal therapy with oral and other
treatments might yield the best results.42 Our standard proto-
col utilizes a combination of pentoxifylline 400 mg t.i.d.,
L-citrulline 750 mg b.i.d. and tadalafil 5 mg daily (if concur-
rent ED is present).41
Topical therapy
Several topical agents have also been investigated. Verapamil
is a calcium channel blocker commonly used to treat hyper-
tension, angina pectoris and headaches, which prevents pro-
line incorporation into the extracellular matrix protein within
scar tissue.43–45 This causes upregulation of collagenase by
fibroblasts.45,46 To date, in vivo studies examining topical
verapamil have shown variable results. One study randomized
57 men to verapamil, trifluoperazine (a calmodulin blocker)
and magnesium sulfate (weaker calcium channel
blocker).47 The authors reported subjective curvature
improvement in >90% of men, but lacked objective measure-
ments.47 Furthermore, Martin et al. found that topical vera-
pamil does not aggregate in detectable levels within the
tunica.48
EMDA utilizes an electrical charge gradient to promote tis-
sue penetration, and has been studied as a means to promote
transdermal drug delivery. Our group identified low, but
detectable, levels of verapamil within the tunica albuginea
after EMDA.49 Di Stasi et al. reported a significant decrease
in penile curvature from 43° to 21° with verapamil + EMDA,
compared with no change in a placebo group.50 In contrast, a
small (n = 42) randomized placebo-controlled trial showed
no significant difference in the number of patients who expe-
rienced curvature improvement with verapamil + EMDA
(65%, mean improvement 9.1°) versus control (58%, mean
improvement 7.6°).51 Because of a lack of supportive data,
and the relatively burdensome administration protocol,
experts recommend against verapamil + EMDA.12
Another recent study reported outcomes in a small cohort
of patients randomized to topical placebo versus “H-100” gel,
a novel compound consisting of nicardipine, superoxide
dismutase and emu oil (purported to enhance tissue penetra-
tion).52 The study was underpowered, but patients in the
“H-100” cohort experienced significant improvements in SPL
© 2020 The Japanese Urological Association
Contemporary Peyronie’s disease management
and curvature. Further studies are necessary before this treat-
ment can be considered standard of care.
SWT
A shockwave is a mechanical disturbance that propagates
through a medium and carries energy.53 Several devices are
available to apply local SWT to the penis, and have been
hypothesized to cause mechanical disruption leading to scar
remodeling and lysis. A meta-analysis found that SWT for
PD improves penile pain and plaque volume, without signifi-
cant impact on curvature.54,55 As a result of significant
methodological flaws, the true impact of SWT on PD remains
unclear, and further research is required. Furthermore, no ran-
domized trials examining the efficacy of low-intensity SWT
(such as that used to treat ED) have been reported. In the
meantime, both the AUA and CUA support the use of SWT
for penile pain as a result of PD, but not penile curva-
ture.12,36
Mechanical therapy
Mechanical therapy refers to the application of force to the
penis by external PTT or VT. This induces a process known
as “mechanotransduction.” Traction was originally used in
the Dupuytren’s contracture population.56 In contrast to the
traditional “bench-to-bedside” paradigm, mechanical therapy
was studied in the clinical realm for PD and only later with
basic science studies.57,58
PTT might be used as monotherapy or as part of a treat-
ment protocol with oral therapy and ILI. The first published
report was a 2008 pilot study by our group involving 10
patients who utilized PTT for 2–8 h daily for 6 months.59 All
patients had objective curvature improvement (10–45°) along
with improvements in SPL (0.5–2 cm). A subsequent study
by Gontero et al. reported a mean 1.3-cm SPL increase,
although curvature was not significantly changed (31° pre-
treatment and 27° post-treatment).60 A larger, prospective
study of 96 men with acute phase PD compared PTT with no
intervention and found a mean 20° decrease in the PTT group
at 9 months, compared with objective worsening in the con-
trol group.33 Symptom duration <3 months and starting cur-
vature <45° were associated with better outcomes.
Traction duration appears to play an important role in out-
comes. Abern et al. found that patients who utilized PTT for
≥3 h daily, in conjunction with intralesional verapamil and
oral L-arginine/pentoxifylline, had mean SPL improvement of
0.6 cm compared with 0.7-cm loss in those who used PTT
<3 h.42 A study by Yafi et al. similarly reported that PTT
use >3 h per day was associated with improved SPL for men
receiving intralesional interferon.61 In contrast, Ziegelmann
et al. did not find any significant difference in outcomes
based on PTT duration in a cohort of patients who underwent
intralesional CCH with or without concurrent PTT.62 Nota-
bly, just 25% of patients used PTT for the recommended
>3 h daily, emphasizing the real-world challenges inherent
with PTT.
A recent study by Moncada et al. randomized patients with
PD (symptom duration ≥1 year and no prior treatment) to
3
MJ ZIEGELMANN ET AL.
PTT with the Penimaster Pro (MSP Concept, Berlin, Ger-
many) or no traction for a period of 12 weeks.63 Patients
were instructed to use the device for 3–8 h daily. A total of
80 patients completed the study protocol and were available
for follow up. The mean curvature improvement was 31° in
the PTT cohort. Patients who utilized the device <4 h a day
experienced a mean curve improvement of 20° compared
with 38° in those who used PTT >6 h per day. There were
also significant improvements in SPL.22,63 Limitations include
that only patients who complied with recommended PTT
duration were included in the analysis (as-treated), and the
cohort included only patients with uniplanar curvature >45°
without indentation deformity who had not undergone prior
therapy. Another study by Ziegelmann et al. evaluated out-
comes with a new traction system known as the Restorex
(Pathright Medical, Plymouth, MN, USA).64 A total of 100
patients were randomized to PTT daily for 30–90 min versus
no traction for 3 months. Using an intent-to-treat analysis, the
authors reported a significant improvement in penile curva-
ture (!11.7° vs +1.3°) and SPL (+1.5 cm vs 0 cm) when
comparing patients in the treatment arms with controls. More
than 75% of patients showed an improvement in curvature,
and nearly 95% had an improvement in SPL. To date, this is
the most rigorous study on PTT and the first study to show
improvements with PTT duration <3–8 h daily. Ultimately,
further data are required to determine the long-term sustain-
ability of these and other published results. With documented
efficacy in both acute and chronic PD, as well as evidence
supporting length restoration and girth improvement, traction
therapy should be recommended to virtually all patients with
PD.
Intralesional injections
ILI therapy refers to the process of injecting medication
directly into plaque, representing a less invasive treatment
modality with proven benefits.65 There are also data to sup-
port ILI for penile pain and possibly even girth and length
recovery when used in combination with other treatment
modalities.42,66 During the past several decades, a variety of
ILI agents, including hyaluronic acid, botulinum toxin and
thiocolchicine, have been studied. However, the most com-
mon agents used in clinical practice today include verapamil,
IFN and CCH (Table 2).65
Verapamil
In 1994, our group first used intralesional verapamil in a non-
randomized dose-escalating study of 14 PD patients.67 Subjec-
tive improvements in narrowing and curvature were reported
in 100% and 43%, respectively. A subsequent study reported
outcomes for 140 men, with average curvature improvement
of 17° and >80% reporting girth improvement.68 A prospec-
tive series found that >95% of men showed improvement or
resolution of penile pain as well.69,70 In contrast, Shirazi et al.
failed to identify a difference in curvature or pain between
patients undergoing verapamil and saline control.71 Side-ef-
fects are generally mild, and include transient pain (mitigated
by penile block) and bruising. A recent systematic review
4 © 2020 The Japanese Urological Association
concluded that the evidence to support ILI verapamil is less
robust when compared with other intralesional agents, such as
IFN and CCH.65 However, due to modest yet favorable
results, low cost and lack of severe side-effects, verapamil is
still utilized by many authorities as first-line therapy, particu-
larly in the acute phase or in those with active pain.12
IFN alfa-2b
IFN exerts its effects on PD plaque by concentration-depen-
dent fibroblast inhibition and decreased collagen production
(upregulated collagenase activity).72 Wegner et al. first
reported their experience with intralesional IFN in 1995.73 A
subsequent pilot study by Ahuja et al. (n = 20) found that
pain resolved in 90% of patients, with curvature improving in
20–90% of patients (mean 65%).74 Later, Hellstrom et al.
carried out a multicenter, single-blind, placebo-controlled
study comparing intralesional IFN (5 million units in 10 cc
of saline administered every other week; n = 50) with pla-
cebo (n = 53), finding a mean penile curvature improvement
of 13.5° (27%) in the IFN group compared with just 4.4°
(9%) in the placebo group (P < 0.001).75,76 Pain improved in
67% of IFN patients compared with 28% of controls. A com-
parison of men treated with IFN for dorsal and ventral pla-
ques showed similar outcomes, with >50% having ≥20%
improvement in penile curvature.77 Side-effects with IFN are
mild-to-moderate, and include ecchymosis, pain, sinusitis,
fever, chills and arthralgias.75 These tend to be short-lived
and adequately managed with anti-inflammatory medications.
Based on data from two randomized, placebo-controlled tri-
als, intralesional IFN provides modest improvement in penile
curvature and might hasten penile pain improvement.75,76
Collagenase Clostridium histolyticum
CCH (Xiaflex; Endo Pharmaceuticals, Dublin, Ireland) is the
newest intralesional agent available, and has gained consider-
able interest since the original phase III study was published
in 2013.7 CCH breaks down collagen types I/III, which are
the main components of PD plaque. CCH is also used to treat
Dupuytren’s contractures.78,79 The original clinical applica-
tion of CCH to PD dates back to 1985, when Gelbard et al.
published a phase I single-arm trial; prior in vitro studies
served as the foundation for this innovative work.80,81 A sub-
sequent phase IIb study randomized patients to CCH versus
placebo with and without provider-applied manual modeling
(bending the flaccid penis in the direction opposite the curva-
ture).82 The authors identified a significant improvement in
penile curvature in those who underwent CCH with modeling
(mean 17.5° or !32%) compared with those who underwent
placebo and modeling (mean 0.6° or +2.5%; P < 0.001).
Interestingly, there was no significant difference between
CCH and placebo in the patients randomized to the non-mod-
eling arm, emphasizing the importance of modeling itself.
Phase III data once again showed a significantly greater
improvement in curvature for those who underwent CCH
(!17° or !34%) compared with placebo (!9° or !18%;
P < 0.0001), along with greater improvement in the patient
bother domain of PDQ.7 The original data from the phase III
 Contemporary Peyronie’s disease management

Table 2 Randomized, placebo-controlled trials for intralesional therapy with CCH, IFN and verapamil

Post-treatment Change in penile

Intralesional Baseline penile penile curvature curvature, mean
Study Design agent Patients curvature (degrees) (degrees) (degrees) Follow up
Gelbard Randomized, CCH CCH (n = 401) CCH: 50.1 (SD 14.4) CCH: 33.1 (SD 16.8) CCH: !17.3 52 weeks
et al.7 double-blind, Placebo (n = 211) Placebo: 49.3 (SD 14.0) Placebo: 40.0 (SD 16.2) Placebo: !9.3
placebo-controlled
Hellstrom Randomized, single-blind, IFN IFN (n = 50) IFN: 49.9 (SD 2.4) IFN: 36.4 (SD 2.1) IFN: !13.5 >4 weeks
et al.75 placebo-controlled Placebo (n = 53) Placebo: 50.9 (SD 2.5) Placebo: 46.4 (SD 2.2) Placebo: !4.5
Shirazi Randomized, Verapamil Verapamil (n = 40) Verapamil: 49.7 (SD 9.3) Verapamil: 47.6 (SD 7.3) Verapamil: !2.1 24 weeks
et al.71 placebo-controlled Placebo (n = 40) Placebo: 45.6 (SD 9.7) Placebo: 43.4 (SD 8.9) Placebo: !2.2
Rehman Randomized, Verapamil Verapamil (n = 7) Verapamil: 37.7 (SD 9.3) Verapamil: 29.6 (SD 7.3) Verapamil: !8.1 3 months
et al.157 single-blinded, Placebo (n = 7) Placebo: 33.6 (SD 9.7) Placebo: 31.4 (SD 8.9) Placebo: !2.2
placebo-controlled

studies included patients with dorsal or dorsolateral penile
curvature of 30–90° in the chronic phase (>12 months since
diagnosis with “stable” disease).7 Exclusion criteria included
isolated hourglass penile deformity, ED, ventral curvature
and significant plaque calcification. Subsequent series have
reported improvements ranging from 5° to 26°, with less
stringent inclusion criteria.79 A multicenter retrospective ser-
ies of 918 patients found a mean improvement of 15.3°, with
nearly 70% of patients having >20% curvature improvement.
Attempts to identify those patients most likely to respond to
CCH have been limited, but data suggest that lack of plaque
calcification, greater disease duration and higher baseline
International Index of Erectile Function scores might be asso-
ciated with better results.30,83 Currently, based on our exten-
sive experience with ILI, we recommend CCH for patients
with mild-to-moderate curvature (<60°) who have an acute
angle of curvature (rather than an extended crescent-type
curve) and minimal plaque calcification.84
The original CCH protocol involved up to four injection
cycles.7 Each cycle consists of two injections of 0.58 mg
CCH directly into the PD plaque, with an interval between
injections of 1–3 days. Patients were instructed to carry out
manual modeling daily during the 6-week interval between
treatment cycles. Recently, several modified protocols have
been reported. Abdel Raheem et al. administered a larger
dose (0.9 mg) once every 4 weeks for a total of three injec-
tions combined with manual modeling at home and VT.85
They found a mean improvement in penile curvature of 17°
or 34%. Adjunctive PTT might also increase treatment effi-
cacy. Alom et al. reported a mean 34° improvement in a
cohort of patients who utilized daily PTT (with the Restorex
traction system) concurrently with CCH treatment.66 This
was significantly greater than those patients who elected to
forego PTT (20°). Finally, recent reports suggest that CCH
has a positive impact during the acute phase and in those
with ventral curvature.34,86
Despite the ongoing enthusiasm for CCH, it is worth not-
ing that even in the CCH arm of the phase III trials just 46%
of patients met the predefined criteria of “composite respon-
der,” which was defined as a ≥20% improvement in curvature
and >1-point PDQ bother score reduction, or change from
reporting no sexual activity at screening to sexual activity.7
Also, a post-approval study from Tsambarlis et al. found less
promising results in a cohort of 45 men who underwent CCH
with a mean reduction of curvature of 5.4°.87 In comparison,
many series reporting results for surgical straightening with
plication or grafting techniques have found success rates,
defined by most authorities as a “functionally” straight penis
with residual curvature <10–20°, in excess of 90%.35 This is
true even in the setting of relatively complex deformities. Not
surprisingly, a recent prospective analysis comparing CCH
with TAP and partial excision and grafting found superior
curvature correction with surgical straightening.88
Another important consideration is the potential side-ef-
fects associated with CCH. Penile ecchymosis and swelling
are seen in up to 80% and 55% of patients treated with CCH,
respectively. Significant penile hematoma and overt corporal
rupture are, thankfully, quite rare, with reported incidence
ranging from 0.5–5% and 0.8–1.4%, respectively.75,89
Although many providers encounter these complications,
there is no consensus on management strategies. Hematomas
might be managed with observation, local compression and
aspiration if associated with discomfort. Some experts closely
observe patients in the setting of possible CCH-associated
corporal rupture, yet approximately two-thirds of surveyed
Sexual Medicine Society of North America members advo-
cated for surgical management.90 Notably, surgical planes
and tissue quality are altered, so surgeon expertise is manda-
tory if operative intervention is undertaken.91
In conclusion, many patients with PD, and, in particular,
those with mild-to-moderate penile deformity, are hesitant to
undergo surgical straightening. ILI might provide modest
improvement in penile curvature, pain, and other types of
deformity, such as girth loss. To date, no head-to-head com-
parisons between CCH and other intralesional therapies have
been published, and future work is necessary to elucidate
those patients who are most likely to benefit from ILI, which
is particularly relevant given the real cost and time commit-
ment with these treatments.
Surgery
For the patient with bothersome penile curvature or severe
indentation deformity that limits the ability to engage in

© 2020 The Japanese Urological Association 5

MJ ZIEGELMANN ET AL.

Peyronie’s Disease

Symptom Duration > 1 year Symptom Duration < 1 year

or
Deformity Stable > 3-6 months Deformity Stable > 3-6 months

“Chronic Phase” “Acute Phase”

No Treatment Options:
Does Patient Desire Surgery?
• Observation
Yes • Oral Therapy
• Traction
Erectile Function • Intralesional injections

Good Non-reponsive to PDE5 inhibitors

Penile Curvature > 60º? Penile Prosthesis Insertion

Indentation Deformity? +/- Straightening Maneuvers
• Notching • Manual Modelling
• Hourglass • Plication
• Hinge-effect • Incision & Grafting
• Length Restoration
No Yes
Yes

Penile Plication Procedure Risk Factors for ED Present

No

Tunical Incision/Excision and Grafting Procedure

(May consider if ED risk factors present, but must discuss risk of worsened ED)
Fig. 1 General algorithm for PD treatment based
on symptom duration and stability.

satisfactory penetrative intercourse, surgery remains the most
rapid and reliable treatment option. The majority of surgeons,
even amongst those with expertise in sexual medicine, carry
out <10 penile plications and penile grafting procedures per
year.92 This is due in part to referral patterns and practice
centralization. Concerns regarding the risk for postoperative
complications and patient dissatisfaction might also drive
some providers to alternative, less invasive (but also less
definitive) treatment options, such as ILI. The surgical
approach is dependent on a variety of factors including penile
deformity (curvature, indentation, hinge effect) and baseline
erectile function (Fig. 1). It is generally agreed upon that sur-
gical straightening should be carried out only after the patient
enters the chronic phase of the disease.92
Penile plication or corporoplasty
Penile plication or corporoplasty, also referred to as “shorten-
ing” procedures, are broadly categorized into incisional or
excisional corporoplasty, and non-incisional plication.93 All
are based on the principle that shortening the convex-side
opposite the area of curvature will pull the penis straight
during an erection. This approach is indicated for those men
with relatively mild-to-moderate curvature (<60–70°), satis-
factory preoperative erections with or without oral therapy,
and the absence of penile instability (i.e. buckling when axial
pressure is applied to the penis such as during penetrative
sexual intercourse).
Corporoplasty refers to full-thickness excision of tunical
tissue and subsequent closure with a non-absorbable suture.
The original approach described by Nesbit involved excision
of an elliptical segment of the tunica albuginea along the cor-
pora opposite the area of maximal curvature, with the defect
closed in a running fashion.94,95 Yachia modified this
approach by making a longitudinal incision and that was
closed horizontally.96 In contrast, true “corporal plication”
refers to suture placement with full-thickness tunical incision.
In 1985, Essed and Schroeder described their plication tech-
nique using non-absorbable sutures to bunch or “plicate” the
corporal tissue.97 Knispel et al. subsequently modified this
technique by inverting the sutures to minimize palpabil-
ity.97,98
TAP was adapted by Levine from the approach described
first by Baskin and Duckett in 1994 to treat pediatric

6 © 2020 The Japanese Urological Association


(a)
Fig. 2 TAP is carried out by excising a portion
of the outer longitudinal tunical fibers and
maintaining the inner circular fibers in the area
opposite to the point of maximum penile
curvature. (a) A 2-0 permanent suture is then
used to bring the edges of the excised tissue
together (b) in a manner that buries the suture
knot.
chordee.99,100 With this technique, partial thickness incisions
(0.5–2 cm in length and maximum distance 0.5–1 cm
between incisions) are made transversely through the outer
longitudinal tunical fibers in the area opposite the curvature,
with care taken to preserve the inner circular fibers (Fig. 2).
The intervening longitudinal fibers are sharply excised so as
to reduce tissue bulk between the incisions. The incisions are
then approximated with a permanent suture using a near-far,
far-near approach (inverting vertical mattress) to bury the
knot. This suture is then reinforced using two adjacent
absorbable 3-0 PDS sutures (Johnson and Johnson, New
Brunswick, NJ, USA) in a Lembert fashion. The 16-dot plica-
tion popularized by Lue involves placement of a non-ab-
sorbable braided-suture along the tunica on the convex side
of the penis in an extended Lembert fashion.101 In the setting
of a broad “banana-type” curvature, more “dots” might be
necessary to completely correct the curvature.93 Finally,
Morey reported excellent results with plication using non-ab-
sorbable braided suture placement through a small 2-cm
penoscrotal incision.102
Success rates reported in the literature vary widely due in
part to significant variation in follow-up duration, the defini-
tion of success and the type of surgical approach. Successful
straightening postoperatively ranges 29–100% with overall
patient satisfaction ranging 65–96%.35 Palpable knots are
reported in 50–100% of procedures, but significant bother
associated with this palpability is substantially lower, ranging
0–20%.35,93,103 Some authors have also reported satisfactory
success rates with absorbable sutures to further minimize knot
palpability while maintaining adequate straightening.14,105
Penile shortening is a major concern for most patients.
Subjective length loss is reported in up to 75% of patients
postoperatively, whereas objective loss, as determined by var-
ious provider-performed assessments of penile length, is seen
in 20–40% of patients.93 Shortening is more common in men
with ventral and ventrolateral penile curvature, and in those
with more severe curvature (>60°).99 This might be mitigated
© 2020 The Japanese Urological Association
Contemporary Peyronie’s disease management
(b)
by carrying out adjunctive maneuvers, such as preoperative
and postoperative PTT.99,106,107 To date, there is no strong
evidence to support one incisional/excisional corporoplasty or
plication technique over another with respect to optimizing
postoperative outcomes. Thus, based on expert opinion, the
operative approach should be left to the discretion of the sur-
geon.18
Plaque incision or partial excision with
grafting
Plaque incision or partial excision with grafting is reserved
for men with excellent baseline erectile function, more severe
curvature (>60–70°) and/or significant penile indentation or
hourglass deformity that creates a hinge effect.19 Grafting
might also be considered for men who have significant con-
cerns about penile shortening and more moderate deformities.
Patient selection is of the utmost importance with grafting
procedures. Because of the increased risk for postoperative
ED, patients with severe deformity and baseline ED (such as
those with poor rigidity despite PDE5Is) should be encour-
aged to pursue penile prosthesis placement with concurrent
straightening maneuvers. Notably, ventral grafting might pre-
dispose patients to increased risk for postoperative ED, and
some experts advocate against grafting procedures for sev-
ere ventral and ventrolateral curvature.110
The decision to carry out plaque incision versus partial pla-
que excision is highly surgeon dependent. During plaque
incision, the surgeon creates a “modified-H” or “double-Y”
tunical defect at the point of maximal curvature.111 In con-
trast, partial plaque excision involves the removal of a seg-
ment of diseased tunic from the area of greatest deformity,
either as an elliptical or a rectangular segment.112,113 To date,
no head-to-head trial has compared outcomes between these
two approaches. Advocates of plaque incision emphasize the
smaller defect size that can be created – small series have
suggested that larger grafts (in excess of 2–4 9 5 cm) might
7
MJ ZIEGELMANN ET AL.
be associated with a higher risk for postoperative ED, pre-
sumably as a result of veno-occlusive dysfunction.110,114
Advocates of partial plaque excision emphasize the ability to
restore more uniform penile girth with indentation deformi-
ties, which in severe cases might result in penile instabil-
ity.113 Furthermore, in the case of a more broad-based penile
curvature, plaque incision alone might not fully correct the
deformity, resulting in the need for plication sutures or even
multiple tunical incisions (and thus multiple separate
grafts).115
Graft selection is an area of ongoing debate, and a compre-
hensive description of the various graft types is beyond the
scope of the current review. To date, there are no strong
comparative data to support the superiority of one graft over
another. The exception to this statement is with synthetic
grafts, which are associated with marked inflammation, fibro-
sis and even graft infection.116,117 Therefore, synthetic grafts
are no longer advocated as first-line treatment. PD grafts can
be generally categorized into autologous and non-autologous
materials.35,118,119 Autologous grafts, such as dermis, saphe-
nous vein, oral mucosa, tunica vaginalis and fascia lata, are
readily available and do not pose the theoretical risk for graft
rejection. However, increased operative times, graft contrac-
tion and harvest site complications are a concern. In contrast,
non-autologous “off the shelf” xenografts and allografts add
Graft
Fig. 3 Complete straightening is achieved with partial plaque excision and
grafting using a Tutoplast human pericardium graft. This approach is indi-
cated for patients with more severe penile curvature (>60–70°, severe inden-
tation or “hinge effect,” or penile shortening).
8 © 2020 The Japanese Urological Association
greater expense, but allow for shorter operative times without
the risk for complications related to graft harvesting. Our pre-
ferred graft is the Tutoplast (Coloplast Corporation, Humle-
baek, Germany) processed human pericardium, because it is
readily available, thin yet strong and in our extensive experi-
ence is less prone to contraction (Fig. 3). Recently, Hatzi-
christodoulou has popularized the use of an equine collagen
fleece known as TachoSil (Baxter, Deerfield, IL, USA).120
The purported benefit of this graft is the ability to apply the
material directly over the tunical defect without suturing it
into place, saving significant time in the operating theater.
Yet, there are concerns regarding the ability to assess penile
straightness intraoperatively. Longer-term follow up and mul-
ti-institution validation are necessary before this approach can
be considered standard of care.
The majority of studies consist of single-institution retro-
spective series focusing on single graft types, thereby limiting
the reliability of results reported in the currently available lit-
erature. Successful penile straightening, defined by some
authorities as a “functionally straight” penis with residual cur-
vature <20–30°, is often based on subjective reporting. Suc-
cess rates range from 55 to 100%, and this might actually
decrease over time.118,121 Patient satisfaction rates, which
take into account not only straightness, but also other aspects,
such as postoperative penile length and erectile function, are
similarly variable, ranging from 60 to 100%.35 Postoperative
complications that compromise patient satisfaction include
perceived penile shortening (0–90%) and penile sensory
changes (0–22%).35,118,122 Sensory changes are transient in
the majority of patients, and a recent report from Terrier
et al. found that, although 20% of men experienced some
degree of glans hypoesthesia at 1 month after grafting, just
3% had persistent deficits at 12 months postoperatively.122,123
Subjective and objective penile length loss can also be
allayed by postoperative penile rehabilitation with PTT or
VT.17,124
Arguably, the most feared postoperative complication is
ED, which is reported in 0–63% in modern series.35,118 Sug-
gested risk factors include greater penile curvature, older age
and larger graft size.110,125 In our extensive experience with
partial plaque excision, we did not identify any significant
difference in the rate of postoperative ED based on graft size
or baseline medical comorbidities.126,127 In fact, the best pre-
dictor of postoperative erectile function is strong and reliable
preoperative erections.127 Ventral graft placement, which
requires urethral mobilization, has also been suggested as an
independent risk factor for postoperative ED.13,110 Therefore,
in the setting of severe ventral curvature, where plication
alone is unlikely to result in satisfactory curvature correction,
penile prosthesis placement with concurrent straightening
maneuvers should be strongly considered.
Penile prosthesis placement with
straightening maneuvers
Penile prosthesis placement with straightening maneuvers
allows for satisfactory penile straightening along with reliable
penile rigidity.26,109 Prosthesis placement might also be con-
sidered in men with more severe penile curvature (>60–70°,
 Contemporary Peyronie’s disease management

significant indentation deformity resulting in hinge effect) current of ≤30 Watts to prevent injury to the underlying
who would otherwise be candidates for grafting procedures, cylinders.140 Incision alone might be all that is necessary, but
but have significant baseline medical comorbidities known to placement of a graft is recommended if the defect is >2 cm
increase their risk for developing ED over time (i.e. hyperten- in greatest dimension, particularly if using an inflatable
sion, hyperlipidemia, diabetes, tobacco use etc.), or in those device – a larger defect might predispose to device aneur-
with severe ventral curvature as a result of the significant risk ysm.141 The graft itself also helps with hemostasis and
for postoperative ED posed by ventral grafting, as previously reduces bothersome cicatrix formation, without increased risk
noted.26,110,128 of device failure or infection.134 Any of the traditional autolo-
The IPP is favored for men with PD because of concerns gous and non-autologous grafts can be used, but because of
regarding persistent deformity, lack of girth enhancement, increased operative times and the risk for damage to the
limited concealment and even partner dissatisfaction, but underlying cylinders with suture placement, there is now a
recent work has found reported high patient satisfaction rates trend toward utilizing sutureless grafts or “patches,” such as
with malleable prostheses as well.129–131 This has important Tachosil or Evarrest (Ethicon, Somerville, NJ, USA), a cellu-
implications, as malleable devices are more accessible and lose mesh containing thrombin and fibrinogen (Fig. 4).142,143
less expensive in some regions of the world. A comparison These materials are hypothesized to provide structural support
between the Coloplast Titan (Coloplast Corporation) and and ingrowth of native tissue in the area of plaque incision.
AMS CX 700 (Boston Scientific, Marlborough, MA, USA) In a manner similar to grafting without a prosthesis, this
showed similar outcomes with respect to penile straightening approach requires mobilization of Buck’s fascia (for dorsal or
and patient satisfaction (nearly 80%).132 In contrast, because lateral curvatures) or the urethra (for ventral curvatures).
of the intrinsic properties that allow for girth and length Thus, patients should be counseled regarding the possibility
expansion, the AMS LGX IPP (Boston Scientific) might actu- of temporary or permanent (albeit rare) glans hypoesthe-
ally exacerbate penile deformity, and this model is not rec- sia.120,144
ommended for men with PD.133 Satisfaction rates with penile prosthesis placement in the
Penile prosthesis placement alone might correct the defor- modern literature often exceed 80–90% for patients and their
mity in relatively mild cases, but additional straightening
maneuvers are required in 30–95% of patients.134–136 Once
again, defining “successful” straightening is not straightfor-
ward. We found that >25% of all patients undergoing IPP
plus straightening maneuvers were dissatisfied with their
penile straightness postoperatively.134 This was despite
achieving a “functionally straight” result (<20° residual cur-
vature) in the operating room in all cases. It is therefore criti-
cal to discuss the patient’s acceptance of functional
straightness (within 20° of straight, as opposed to “arrow”
straightness) during preoperative counseling. When residual
curvature is present, a variety of intraoperative maneuvers are
utilized. Wilson and Delk were the first to describe manual
modeling for residual curvature beyond 20–30° after IPP.137
With this technique, the penis is forcefully bent in the direc-
tion opposite the curvature while the prosthesis cylinders are
maximally inflated. Several series have reported success rates
ranging from 80 to 100%, yet there is a known risk for ure-
thral injury (perforation of the fossa navicularis as a result of
excessive pressure on the distal cylinder tips).133–134,137
Penile plication sutures, placed before the cylinders, are
another approach to address moderate residual curvature.138.
If adequate curvature correction is achieved through prosthe-
sis placement alone, the sutures can simply be removed.
Notably, although plication might correct penile curvature,
this approach could result in further penile shortening, which
is already a significant concern for most men undergoing
penile prosthesis.139 Furthermore, plication will not address
severe indentation deformity and has the potential to actually
exacerbate penile instability, even with the added rigidity of
the prosthesis.
Fig. 4 Penile prosthesis placement followed by plaque incision and hemo-
Plaque incision with or without grafting should be consid- static patch placement in a patient with coincident severe ED and PD. When
ered when there is residual curvature >30° or severe indenta- penile prosthesis placement alone does not result in satisfactory straightening,
tion deformity. An incision is made in the tunic overlying the adjunctive straightening maneuvers, such as manual modeling, penile plication,
prosthesis at the area of greatest deformity using coagulation and plaque incision and grafting (shown here), might be required.

© 2020 The Japanese Urological Association 9

MJ ZIEGELMANN ET AL.
partners.145-148 In their multicenter prospective series, Khera
et al. found that >80% of PD patients reported feeling some-
what or very satisfied with their IPP, and there was no signif-
icant difference in the satisfaction rate when compared with
patients without PD.149 To date, there are no strong data to
suggest that PD predisposes to adverse outcomes, such as
infection or shortened device survival, even when modeling
or grafting is carried out.134,150,151 However, prospective data
comparing outcomes in men with and without PD are lacking
and further study is required.
As a final note, the concept of penile length restoration
deserves special mention. Over the past decade, several tech-
niques have been developed and refined to optimize penile
length in the setting of PD and prosthesis placement. Exam-
ples include circumferential tunical grafting and the sliding
technique, wherein hemicircular incisions are made along the
dorsal (proximal) and ventral (distal) corpora after elevation
of the neurovascular bundle and urethra.152,153 These inci-
sions are then connected by bilateral longitudinal incisions
with subsequent grafting, which might involve a substantial
amount of suturing if traditional graft materials are used.
Refinements to the sliding technique by Egydio et al. were
developed to avoid the need for graft placement by utilizing
Buck’s fascia (MoST) or a smaller series of tunical defects
(MuST).154,155 It must be emphasized that, although rare,
serious and irreversible side-effects, including glans necrosis,
might occur with these approaches as a result of vascular
compromise.156 Thus, length restoration procedures should
only be carried out by experienced surgeons after thorough
patient counseling.
Conclusions
PD is a condition characterized by penile deformity, pain,
sexual dysfunction and psychological bother. The first step is
to characterize the presenting symptoms, disease duration and
level of bother through a detailed history and examination. In
a man who desires active treatment, a formal curvature
assessment must be carried out to objectively characterize the
penile deformity. Depending on the symptom severity, a vari-
ety of treatment options, including PTT, ILI and surgical
straightening, are available with varying efficacy.
Conflict of interest
Dr Laurence Levine is a consultant for Boston Scientific and
Coloplast Corporation. The other authors declare no conflict
of interest.
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