Low-intensity extracorporeal shockwave therapy for Peyronie's disease: An Indian experience (2024)

Abstract

INTRODUCTION

The first published paper on the thickened plaque in tunica albuginea layer of penis was in 1743 by de la Peyronie.[1] The incidence of PD ranges from 0.39% to 20.3% in adult male population.[2] The pathogenesis and management of PD is still uncertain. The current etiology of PD is proposed to be abnormal wound-healing response after an injury to tunica albuginea layer of the penis.[3] This results in a scar which undergoes abnormal remodeling. Therefore, there is persistent deformity.[4,5,6,7,8] Full spontaneous resolution of PD is a rare phenomenon.

Conservative therapies do not provide cure for PD. Surgery is the definitive treatment for correcting the penile curvature but has the potential risk of penile shortening, erectile dysfunction (ED), and decreased penile sensation. Bellorofonte et al. in 1989 first proposed the use of shockwave therapy for cavernous fibrosis.[9] Palmieri et al. in 2009 reported the first randomized trial for evaluating extracorporeal shockwave therapy (ESWT) for PD.[10] In this study, we aim to study the efficiency of low-intensity ESWT (LiESWT) for PD in Indian population.

METHODS

From October 2021 till May 2022, we conducted an open-label single-arm prospective clinical study on 25 male patients affected by PD with or without ED. All patients were informed in detail about the available therapeutic options for PD.

After obtaining institutional ethical clearance (IPGME and R/IEC/2021/587 R), patients with written informed consent were enrolled for the study. The inclusion criteria were as follows: stable curvature due to PD ≥ 6 months, age between 18 and 65 years, a single penile plaque demonstrated by high-resolution ultrasonography, and penile curvature on erection ≥30°. Patients were excluded from enrollment for any of the following: lower urinary tract infections, PD with hinge deformity, previous surgical therapies for PD or ED, bleeding tendency or coagulation disorder, comorbidities (diabetes mellitus, lipid disorders, and cardiovascular diseases), premature ejacul*tion, ED due to history of radical prostatectomy, or other pelvic surgery with subsequent ED.

Penile plaque size, penile curvature degree, presence and severity of painful erections (visual analog scale [VAS]), erectile function (International Index of Erectile Function [IIEF] questionnaire-5), and stretched penile length were evaluated at baseline and during 6 months of follow-up. Patients were asked to answer yes/no question: “Do you experience difficulty in vagin*l penetration during sexual intercourse?” The degree of curvature was measured with goniometer or protractor before and after treatment using photographic lateral and dorsal pictures taken by the patients during full erection. In patients with ED, oral tadalafil 10 mg was given and post erection photograph was taken. If the patient had curvature in more than one plane, the plane with maximum deviation was taken as the baseline for further evaluation in the study. Plaque calcification (PC) was confirmed and graded by ultrasound using a 7.5 MHz linear transducer. PC was graded as follows: grade 1 (<0.3 cm), Grade 2 (>0.3 cm and <1.5 cm), and Grade 3 (>1.5 cm; or ≥2 plaques >1.0 cm).[11]

Patients with PD and ED (IIEF-5 <17) were given oral tadalafil (10 mg) daily dose starting 1 week before shockwave and continued for next 6 weeks along the course of Li ESWT [Figure 1]. Li EWST was performed without anesthesia. The adhesive tape was applied over the glans of the flaccid penis. The penis was stretched such that the other end of the adhesive tape was applied over the back of the right or left thigh for dorsal plaque and front of the opposite thigh for lateral plaque. After skin sensitivity test, perilesional injection of 76% urograffin contrast used for plaque localization. The patient was positioned in lateral decubitus position. The shockwave generator arm was rotated to 90° horizontally. The perilesional contrast was focused in both 0° and 30° under the C-arm. After focusing the Peyronie's plaque, lithotripter's coupling cushion was positioned over the skin of the penile plaque. Dornier Compact Delta II lithotripter was used to deliver 1800 shockwaves/session at energy flux density of 0.23 mJ/mm² over the PD plaque [Figure 2]. The Li ESWT course consists of weekly sessions for 6 consecutive weeks. Post-Li ESWT, all patients were followed up for at least 6 months. Improvement in erectile function (IIEF-5 score) was evaluated at the end of the study. At the end of the study, patients responded to the question “Post therapy whether you experience any difference during vagin*l penetration for sexual intercourse?” with better/no change/worse.

The primary outcome was to assess remission of pain and ≥50% reduction of plaques size. Successful remission of pain meant decrease in VAS of ≥4 or complete resolution of pain during erection or vagin*l penetration. The secondary outcome of the treatment was to assess subjective improvement during vagin*l penetration and improvement in erectile function associated with increase of IIEF-5 score ≥3.

The data were tabulated in Microsoft Excel and were analyzed with SPSS (statistics for windows, version 24.0 IBM Corp., Armonk, N.Y., USA). The continuous variables were expressed with mean and standard deviation (SD). The categorical variables were expressed with frequency and percentage. Paired t-test was used for the comparison of the variables between different intervals. P ≤ 0.05 was considered statistically significant.

RESULTS

The mean age of the patients included in the study was 44.36 ± 11.02 years. The duration of the disease was 13.68 ± 7.88 months. Eight patients had taken nonsurgical treatment before being enrolled for this study [Table 1]. All the patients had some discomfort either during erection or sexual activity. The mean pretreatment VAS was 3.2 ± 1.88. The IIEF-5 score was 20.04 ± 2.39. Four patients had IIEF score <17 and were on oral daily 10 mg tadalafil. Thirteen patients had mild ED (IIEF score 17–21). Most plaques were located dorsally over the penis. The mean plaque size was 1.25 ± 0.66 cm in largest dimension. About an average of 44.72° ± 9.28° mean penile deviation was noted. Penile ultrasonography noted PC in 12 (48%) patients [Table 2]. Twenty-two patients had difficulty in vagin*l penetration during intercourse.

At 24 weeks of follow-up, after the final Li ESWT session, more than 50% reduction of plaque size was achieved in 5 (20%) patients. The reduction of mean plaque size in the greatest dimension from 1.25 ± 0.66 cm to 0.94 ± 0.37 cm was found to be significant [Table 2]. Primary goal of pain reduction with decrease in VAS ≥3 score or complete pain resolution (VAS score 0) was achieved in 16 (64%) patients post therapy. The VAS reduction from 3.2 ± 1.88 to 0.8 ± 0.8 was found significant [Table 2]. Only five patients reported subjective improvement in vagin*l penetration during sexual intercourse. Three participants experienced worsening during vagin*l penetration.

The increase in mean IIEF-5 score from 20.04 ± 2.34 to 21.72 ± 1.75 was significant [Table 2]. The IIEF-5 score improvement of ≥3 was found in 9 (36%) patients. None had worsening of erectile function after the treatment.

No significant change in stretched penile length and penile curvature was achieved. Post-ESWT nonsignificant increase in mean stretched penile length was observed [Table 2]. Nonsignificant improvement in mean penile curvature from 44.72° ± 9.28° to 43.12° ± 9.74° was observed [Table 2]. Four patients had no change in penile curvature. Four patients had worsening of penile curvature.

Decrease in grade of PC was observed post-Li ESWT. Complete resolution of penile PC was seen in four patients (two patients each of Grade 1 and Grade 2). Further subanalysis showed that the mean reduction of angle in patients with and without PC after LiESWT was 2.25° ± 4.47° and 1.0° ± 4.72°, respectively.

Posttherapy the mean reduction in VAS in noncalcified plaque participants and in cases with PC was 3 ± 1.47 and 1.73 ± 1.42, respectively. The mean reduction of plaque size in patients with PC from 1.44 ± 0.87 cm to 0.97 ± 0.48 cm was significant (P = 0.03) [Table 2]. The mean reduction of plaque size of 0.16 ± 0.36 in noncalcified plaque was not significant (P = 0.72).

There was no incidence of penile pain, penile swelling, skin hematoma, urethral bleeding in the first void after each Li ESWL course. None of the patient developed urethral stricture during or post shockwave therapy. Among the four patients who took a daily tadalafil 10 mg dose, three reported adverse effect of n asal congestion, dyspepsia, and headache.

DISCUSSION

The exact mechanism for Li ESWT in PD is not known. A probable hypothesis is that low intensity shockwaves induces mechanical trauma leading to inflammatory reaction, neovascularization and plaque lysis by macrophage activity.[12]

The number of shockwaves per session, the number of sessions, and the duration between consecutive sessions for treatment of PD has not been standardized. Our initial proposal of two angle or three angle approach of delivering 12 course shockwave therapy as per plaque size was based on the work by Li et al.[13] However, this was not feasible with the standard lithotripter. Hence, 1800 low-intensity shocks were delivered directly over the plaque in each session. As this study was started during the COVID pandemic, we reduced the ESWT course from 12 to 6. Each session was performed weekly for next 6 consecutive weeks. Follow-up was planned after 6 months. [Figure 1]. We faced difficulty in focusing the Peyronie's plaque and patient positioning using standard Dornier Compact Delta II lithotripter. Based on the study by Lebret et al.,[14] we used perilesional contrast for radiologic localization of plaque.

Similar to most of the previous studies [Table 3], we observed nonsignificant decrease of 1.44° ±4.69° of curvature in mean penile curvature observed at 6-month follow-up (P = 0.0523). There was no significant change in stretched penile length seen. Hauck et al.[16] also observed a nonsignificant (P = 0.078) 5.8° decrease in mean penile curvature. However, subgroup analysis revealed a statistically significant 7.2° decrease in penile curvature in the 31°–60° patient group after therapy (P < 0.003).

Although we found significant (P = 0.0092) mean plaque size in greatest dimension post therapy, only 20% of cases had more than half plaque size reduction. None had complete resolution of plaque. Shimpi and Jain[20] observed a significant decrease in Doppler-measured mean plaque size from 90.3 mm² to 44.08 mm² (P < 0.0001). However, most studies showed a nonstatistically significant decrease in plaque size postshockwave therapy [Table 3].

Posttherapy VAS reduction was found significant (P < 0.00001). The secondary goal of subjective improvement in vagin*l penetration during sexual intercourse was achieved in 20% (n = 5) of cases. The reason for this improvement was due to a significant decrease in pain [Table 2]. Lebret et al.[14] noticed relief immediately after ESWT in 91% of cases. Chitale et al.[18] reported a nonsignificant decrease of 1.1 mean VAS in the shockwave group compared to 0.8 mean VAS decrease in the placebo group (P = 0.679).

The sexual dysfunction in PD may be associated with penile deformity, painful erections, and ED or psychosocial factor. The erectile function IIEF-5 score improvement of ≥3 was achieved only in 36% of cases. Increase IIEF-5 score of ≥3 caused change in ED classification from mild ED to normal and mild-moderate ED to mild ED category in five patients and three patients, respectively. The increase in mean IIEF-5 of 1.68 ± 1.43 was found statistically significant (P < 0.00001) but was not overall clinically significant. Abdel-Salam et al.[17] reported 58% improvement in sexual function, but they had not used IIEF-5. However, Chitale et al.[18] did not report any statistically significant improvement in IIEF-5 in both therapy and sham group. The adverse effects with tadalafil 10 mg used in patients with PD + ED did not warrant discontinuation of the drug during the study.

The mechanism for resorption of calcifications post-LiESWT is not known. Four patients (two each of PC Grade 1 and Grade 2) had complete resolution of penile PC posttherapy. None of the patients developed new calcification during and after shock therapy. Hauck et al.[16] found that post shockwave therapy, 6 patients had resolution of calcification, but three patients developed new PC after treatment.

The impact of PC on the outcome of Li ESWT has not been well studied. The sub-analysis showed that the reduction of penile curvature was almost twice in PC group (n = 12, mean reduction = 2.25°, SD = 4.47) than in plaques without calcification (n = 13, mean reduction = 1.0, SD = 4.72), but this difference was non-significant (P = 0.26). The mean reduction in plaque size was significant in the PC group [Table 2]. The mean plaque size reduction was almost three times in the PC group (n = 12, mean reduction = 0.47 cm, SD = 0.74) than the noncalcified plaque group (n = 13, mean reduction = 0.16 cm, SD = 0.36), but this difference was not significant (P = 0.108) [Table 2]. Furthermore, the mean VAS reduction was about 1.7 times more in the noncalcified plaque than in the calcified plaque group.

Absence of control group, no comparison with other therapeutic modalities, and small sample size are the limitations of this study. Our study results was found to be comparable with other studies [Table 3]. Surgery is the gold standard treatment modality for PD. Based on this study and literature review, shockwave therapy is not a standard treatment for PD but can be used as an alternative treatment modality. However, a randomized controlled trial of long-term treatment sessions with shockwave on larger sample might show positive results.

CONCLUSIONS

Shockwave therapy is a probable alternative to surgery in patients with PD. Significant improvement was observed in pain and plaque size by LiESWT. However, no significant change was seen in penile curvature and penile length. The presence of PC may affect the outcome of Li ESWT in PD.

Footnotes

REFERENCES