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Utility of doppler ultrasound in Peyronie’s disease

Javier Romero-Otero
Hospital Universitario 12 Octubre
HM Hospitales
jromerootero@hotmail.com

Borja García Gomez
Hospital Universitario 12 Octubre
HM Hospitales
gendine@hotmail.com

Historic features

The use of ultrasound in the diagnosis of Peyronie’s disease (PD) was first described by Alteffar and Jordan in a paper published in 1981. They concluded that this technique was useful to demonstrate the plaque itself and its calficication, allowing to identify those patients who will benefit from a medical or surgical treatment.

But it was not until 1991, when Lopez and Jarow described the utility of the duplex ultrasound in the assessment of PD patients. They found evidence of arterial disease in 27 % of the so called “impotent” patients and plaque in only 39 % of the whole group.

Since then, ultrasound has been used in men with PD to localize lesions, follow plaque size, and perform Doppler vascular studies. Among men who are diagnosed with PD but do not have palpable plaques, penile ultrasound is often demonstrative of septal fibrosis, intracavernosal fibrosis, or sub-tunical calcifications. Studies have evaluated the prevalence of calcification in chronic PD and used the presence of calcified plaques as an exclusion criterion for studies of medical treatment of PD.

The current guidelines recommendations

However, nowadays, for the main clinical practice guidelines the duplex ultrasound does not appear to be particularly relevant or to play a significant role in the diagnostic evaluation of patients with PD.

Thereby, the EAU Guidelines on Erectile Dysfunction, Premature Ejaculation, Penile Curvature and Priapism, in the 2019 edition, stablish that “ultrasound measurement of the plaque’s size is inaccurate and operator dependent” (level of evidence -LE- 3), and that “doppler ultrasound is required to ascertain vascular parameters associated with ED (LE 2a). They recommend not to use ultrasound measurement of plaque size in everyday clinical practice (weak). The AUA Guidelines on PD, 2015 version, give an expert opinion recommedation in this situation, in which “clinicians should perform an in-office intracavernosal injection test prior to invasive intervention, with or without duplex doppler Ultrasound”.

In contrast, the Evidence-Based Management Guidelines on Peyronie’s Disease of the European Society for Sexual Medicine, stablish that the penile color duplex ultrasonography (CDU) provides a safe, low-cost, and rapid means of objectively characterizing PD, with a LE 3 and a grade recommendation C.

The lack of good quality evidence in the literature may explain the weak recommendations given in these guidelines. But at the same time, many groups may not be using the doppler ultrasound routinely precisely because these recommendations, with concerns about the real utility of this technique in the assessment of patients with PD.

In recent years, and along with the change in the management of this disease, there has been an increasing evidence to support the routine use of the penile doppler ultrasound in the evaluation of these patients.

The importance of calcification

Besides the confirmation of the presence of a plaque, the description of tunica albuginea thickening (>2 mm for most groups, >3mm for some) and its localization, ultrasound can be easily used to evaluate the calcification of the plaque.

In 2008 Bekos et al. published a prospective series including 95 patients with PD in different stages. They were all classified according to ultrasonographic patterns (“solitary hyperechoic lesions without acoustic shadow (group A), moderately hyperechoic multiple scattered calcified lesions with acoustic shadows (group B), dense calcified hyperechoic plaques with acoustic shadow (group C)”), and were included in a watchful waiting protocol. Ultrasound was repeated after 1 year. 9 of 11 patients in group A (81.8 %) saw a slight improvement, while the 2 other patients developed calcifications. Both the groups B and C saw a progression of the disease with more calcifications and curvature worsening, concluding that patients with “solitary hyperechoic lesions without acoustic shadow” may see a spontaneous resolution or improvement of their affection.

In 2009, Smith et al published the ultrasound findings in a large cohort of 528 patients with PD. They found that any kind of calcification was present in 31.4 % of them, and that other important findings when planning surgery, as septal fibrosis and intracavernosal fibrosis, were present in 6.8 % and 15 % of the patients, respectively. they concluded that ultrasound may help track the evolution of the condition in individual patients and in the future may be useful for tailoring treatment strategies.

This way, the same group published one year later a retrospective study of a cohort of 518 PD patients, in which they found a progression to surgery rate of 25 % after an average follow-up of 1.25 years. Patients who underwent surgery were more likely to have subtunical calcifications present at the first clinic visit (OR 1.75), but no other of the sonographic characteristics analized (tunical thickening, septal or intracavernosal fibrosis) were associated with progression. These findings stood unvariable even after adjustment for age, marital status and PD specific characteristics (duration of symptoms, degree of curvature, penile deformity, penetration difficulty, loss of penile lenght, ability to have intercourse and treatment for PD before enrollement in study).

These findings were confirmed by another paper by Levine et al, in which they analized retrospectively a cohort of 1041 patients with PD. 34 % of them presented with any kind of calcification, and they were graded in 3 different groups: grade 1 (calcification <0.3 cm), grade 2 (>0.3 cm, but <1.5 cm), grade 3 (>1.5 cm; or ≥2 plaques >1.0 cm). Men with grade 3 penile calcification had an increased likelihood of progression to surgical intervention, and a higher likelihood of undergoing a grafting procedure.

Since the approval of the collagenase of the Clostridium histolyticum (CCH; Xiapex®, Swedish Orphan Biovitrum AB, Stockhom, Sweden; Xiaflex®, Endo Pharmaceuticals, Malvern, PA, USA) for the treatment of PD, knowing the status of calcification of the plaque seems to have an increasing importance, as two papers published in 2018 demonstrate. The first, by Wymer et al. is a prospective series of 192 patients with PD who underwent treatment with CCH, and in whom a Doppler ultrasound was performed before and after treatment. Noncalcified plaque (OR 2.50; p=0.03) and curvature ≥60° (OR 5.01; p = 0.02) were found to be significant predictors of ≥20 % improvement in composite curvature. When differentiated by calcification severity, those with no calcification achieved significant improvements in curvature (28.1° vs 10.3°, p = 0.04), compared to moderate (shadowing) or severe (>1 cm).

The second study, by Cocci et al. enrolled 135 patients with PD into a prospective multicentre single-arm. They built a nomogram able to predict treatment success after CCH. When analysing factors associated with penile curvature improvement after treatment, the found that baseline curvature (OR 1.14; p<0.01), basal plaque (OR 64.27; p<0.01), low calcification (OR 0.06; p<0.01) and high calcification (OR 0.03; p<0.01) were significant predictors of curvature improvement. They concluded that patients with longer PD duration, greater baseline curvature and basal plaque location had a greater chance of treatment success, whereas any kind of calcification was associated with poor response.

Vascular assessment of the penis

When combined with an intracavernous injection of an erectogenic medication (e.g. alprostadil), doppler ultrasound may be used to assess penile vascularization along with a direct inspection of the penile malformation (Kelami test). Both end diastolic velocity (EDV) and peak systolic flow (PSF) need to be measured 10 and 20 minutes after a standard administration of 10 µg of alprostadil. Although the measures considered normal may vary depending on the group, is usually defined as a PSV >25 cm/s and a EDV < 5cm/s. In case of an arterial insufficiency, the PSF will be <25 cm/s with normal EDV; and in case of venous leakage, the EDV will be >5 cm/s with a normal PSF.

It is known that when planning a grafting technique to solve PD, the older patients and specially those with cardiovascular risk factors, are more likely to develop and erectile dysfunction after surgery, so they may be offered penile prosthesis implatation with modelling of the fibrous plaque. Doppler ultrasound may help identify more accurately these patients at risk, so counseling should be more efficient.

In conclusion

Better description of plaque’s characteristics, specially the degree of
calcification, seems to be of great importance to understand the potential development of the disease and to optimize and personalize the subsequent treatment. The recent introduction of CCH as a conservative therapy for this disease strenghthens this statement. Besides, knowing the vascular status of the penis with PD may help to counseal adequately the patient in the best surgical approach to avoid complications.

Doppler ultrasound is a relatively low-cost and minimally invasive technique can quickly and efficiently identify these factors. So, for the authors, there are sufficient reasons to routinely perform a doppler ultrasound of the penis in the assessment of patients with PD, at least before planning the better treatment to receive.

References

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  2. Lopez JA, Jarow JP. Duplex ultrasound findings in men with Peyronie‘s disease.Urol Radiol. 1991;12(4):199-202.
  3. Smith JF, Brant WO, Fradet V, Shindel AW, Vittinghoff E, Chi T, et al. Penile Sonographic and Clinical Characteristics in Men with Peyronie’s Disease. The Journal of Sexual Medicine 2009;6:2858–67.
  4. Hatzimouratidis K, Giuliano F, Moncada I, Muneer A, Salonia A, Verze P. EAU Guidelines on Erectile Dysfunction, Premature Ejaculation, Penile Curvature and Priapism. https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Male-Sexual-Dysfunction-2019.pdf.
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  10. Cocci A, Russo GI, Briganti A, Salonia A, Cacciamani G, Capece M, Falcone M, Timpano M, Cito G, Verze P, Giammusso B, Morgia G, Mirone V, Minervini A, Gacci M, Cai T, Serni S, Carini M, Giubilei G, Mondaini N. Predictors of treatment success after collagenase Clostridium histolyticum injection for Peyronie‘s disease: development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study. BJU Int. 2018 Oct;122(4):680-687.
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  13. Garcia-Gomez B, Ralph D, Levine L, Moncada-Iribarren I, Djinovic R, Albersen M, Garcia-Cruz E, Romero-Otero J. Grafts for Peyronie‘s disease: a comprehensive review. Andrology. 2018 Jan;6(1):117-126.
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