Lucio Dell'Atti et al., 2024: Multimodal treatments based on Tadalafil during acute phase of Peyronie's disease: experience at two referral academic centers

Tuesday, 13 August 2024

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Lucio Dell'Atti, Viktoria Slyusar, Chiara Cambise
Division of Urology, Unit of Quality and Risk Management, University-Hospital of Marche, 71 Conca Street, 60126 Torrette, Ancona, Italy.
Division of Anesthesia and intensive Care, University-Hospital of Marche, Ancona, Italy.
Department of Emergency, University-Hospital Gemelli IRCSS, Rome, Italy.

Abstract

Aim: The purpose of this study is to identify the clinical outcomes of patients during acute phase of Peyronie's disease (PD) treated with daily Tadalafil 5 mg associated with non-surgical treatments such as intra-plaque verapamil injections (IVI), vacuum erection devices (VED) or extra corporeal shockwave therapy (ESWT).

Methods: 445 patients with PD in acute stage were treated as it follows: Group 1(G1) 117 men with only Tadalafil 5 mg once a day for 3 months; Group 2(G2) 106 men with IVI plus Tadalafil 5 mg for a period of 12 weeks; Group 3(G3) 124 men that received ESWT for 6 weeks plus Tadalafil with the same protocol of G1; Group 4(G4) 98 men with VED plus Tadalafil 5 mg for 3 months. There were assessed at baseline and follow-up: Erectile dysfunction (ED), presence and severity of painful erections, penile plaque size and penile curvature degree. The results were evaluated at baseline and 3,6,12 months.

Results: Not statistically significant differences emerged between the two groups at baseline, except for higher presence of patients with ED in in G3(7.4%) vs other groups(p < 0.001). Three months after the treatment in G3 men had a significant reduction of penile curvature degrees after 1 year by treatments, whereas pain in an erection or during intercourse was resolved completely in 75% of the patients.

Conclusions: Our study highlights that multimodal therapy has beneficial long-term effects not only in the decrease of ED symptoms, but also in the relief of the penile curvature and the quality of life.

Ir J Med Sci. 2024 Jun 11. doi: 10.1007/s11845-024-03734-1. Online ahead of print
PMID: 38861101 DOI: 10.1007/s11845-024-03734-1

Comments 1

Jens Rassweiler on Tuesday, 13 August 2024 11:00

Peyronie’s disease (PD) is a condition characterized by fibrotic degeneration of the tunica albuginea of the corpora cavernosa. It affects men over 40, with a prevalence ranging from 0.4% to 7%. The disease often progresses from an acute inflammatory phase with plaque formation to a chronic stage where plaques stabilize. Management during the acute stage involves conservative therapies, including oral drugs, intra-plaque injections, mechanical stretching with vacuum erection devices (VED), and extracorporeal shockwave therapy (ESWT). Phosphodiesterase type 5 inhibitors (PDE5i), such as Tadalafil, are used to inhibit tissue remodeling by reducing oxidative stress. This study evaluates the outcomes of Tadalafil combined with non-surgical treatments like intra-plaque verapamil injections, VED, or ESWT.
Materials and Methods
A retrospective analysis was conducted on PD patients treated between January 2012 and May 2023 at two referral andrology centers. Male patients aged 18 and over with active-stage PD, one penile plaque ≤20 mm, penile deviation ≤60°, and associated erectile dysfunction (ED).
Exclusion Criteria: Multiple plaques, prior penile surgery, chronic PD stage, low testosterone, and other conditions.
Data collected included age, previous treatments, comorbidities, plaque size and location, disease duration, penile curvature, ED severity (using the International Index of Erectile Function, IIEF-5), and pain during erection (using the Visual Analog Scale, VAS).
Treatment Protocols
The study included 445 patients divided into four groups:
Group 1 (G1): 117 patients treated with Tadalafil 5 mg daily for 3 months.
Group 2 (G2): 106 patients received weekly Verapamil injections plus Tadalafil 5 mg daily for 3 months.
Group 3 (G3): 124 patients underwent ESWT with incremental energy levels plus Tadalafil 5 mg daily for 3 months.
Group 4 (G4): 98 patients used a VED twice daily for 10 minutes plus Tadalafil 5 mg daily for 3 months.
Baseline characteristics showed no significant differences except for higher ED presence in G3.

Results
Side Effects: Some patients experienced mild side effects from Tadalafil. A few patients in G2 and G3 developed superficial hematomas, but no major adverse events were reported.
Treatment Outcomes:
G3 (ESWT) showed a significant reduction in penile curvature from an average of 32.54° at baseline to 19.36° after one year.
Pain during erection resolved completely in 75% of G3 (ESWT) patients.
No significant differences in plaque sizes were observed at 3 months, but improvements were noted in G3 (ESWT) and G4 (VED) at one year.
G4 (VED) showed significant improvement in IIEF-5 scores for ED.
Discussion
PD’s pathophysiology is not fully understood, complicating treatment. The disease presents with penile curvature, pain, and ED. Non-surgical treatments aim to resolve pain, prevent further curvature, and improve erectile function.
Tadalafil and other PDE5is have shown antifibrotic effects in animal models and are used to improve erectile function in PD patients. Despite their use, evidence of their effectiveness in reducing symptoms is limited.
Combining treatments like Verapamil injections and ESWT with Tadalafil appears logical, though high-quality evidence supporting this approach is lacking. Here ESWT has the significant advantage of non-ivasiveness
Study Limitations
The study’s nonrandomized, retrospective design and small sample size limit its conclusions. Future multicenter studies are needed for validation.
Conclusions
The study suggests that PDE5is, particularly when used in combination with other therapies, can benefit patients during the acute stage of PD by improving sexual function, reducing penile curvature, and decreasing plaque size. Multimodal therapy shows promise for long-term improvement in PD symptoms and quality of life. This represents a complete change of mind-set in the management of the acute phase of Peyronie`s disease. Whereas, initially we have waited until the acute phase became chronic, knowing about the limited effect of the drugs used previously (i.e. Potaba, Vitamin E), we now treat the acute phase effectively, i.e. by combining the antifibrotic effect of Taldalafil with the anti-inflammatory effect and stimulation of stem cells by mechano-transduction.
Unfortunately, this study is only retrospective, however, it provides important information for the design of future studies.

Jens Rassweiler

Results
Side Effects: Some patients experienced mild side effects from Tadalafil. A few patients in G2 and G3 developed superficial hematomas, but no major adverse events were reported.
Treatment Outcomes:
G3 (ESWT) showed a significant reduction in penile curvature from an average of 32.54° at baseline to 19.36° after one year.
Pain during erection resolved completely in 75% of G3 (ESWT) patients.
No significant differences in plaque sizes were observed at 3 months, but improvements were noted in G3 (ESWT) and G4 (VED) at one year.
G4 (VED) showed significant improvement in IIEF-5 scores for ED.
Discussion
PD’s pathophysiology is not fully understood, complicating treatment. The disease presents with penile curvature, pain, and ED. Non-surgical treatments aim to resolve pain, prevent further curvature, and improve erectile function.
Tadalafil and other PDE5is have shown antifibrotic effects in animal models and are used to improve erectile function in PD patients. Despite their use, evidence of their effectiveness in reducing symptoms is limited.
Combining treatments like Verapamil injections and ESWT with Tadalafil appears logical, though high-quality evidence supporting this approach is lacking. Here ESWT has the significant advantage of non-ivasiveness
Study Limitations 
The study’s nonrandomized, retrospective design and small sample size limit its conclusions. Future multicenter studies are needed for validation.
Conclusions
The study suggests that PDE5is, particularly when used in combination with other therapies, can benefit patients during the acute stage of PD by improving sexual function, reducing penile curvature, and decreasing plaque size. Multimodal therapy shows promise for long-term improvement in PD symptoms and quality of life. This represents a complete change of mind-set in the management of the acute phase of Peyronie`s disease. Whereas, initially we have waited until the acute phase became chronic, knowing about the limited effect of the drugs used previously (i.e. Potaba, Vitamin E), we now treat the acute phase effectively, i.e. by combining the antifibrotic effect of Taldalafil with the anti-inflammatory effect and stimulation of stem cells by mechano-transduction.
Unfortunately, this study is only retrospective, however, it provides important information for the design of future studies.

Jens Rassweiler

Peyronie’s disease (PD) is a condition characterized by fibrotic degeneration of the tunica albuginea of the corpora cavernosa. It affects men over 40, with a prevalence ranging from 0.4% to 7%. The disease often progresses from an acute inflammatory phase with plaque formation to a chronic stage where plaques stabilize. Management during the acute stage involves conservative therapies, including oral drugs, intra-plaque injections, mechanical stretching with vacuum erection devices (VED), and extracorporeal shockwave therapy (ESWT). Phosphodiesterase type 5 inhibitors (PDE5i), such as Tadalafil, are used to inhibit tissue remodeling by reducing oxidative stress. This study evaluates the outcomes of Tadalafil combined with non-surgical treatments like intra-plaque verapamil injections, VED, or ESWT. Materials and Methods A retrospective analysis was conducted on PD patients treated between January 2012 and May 2023 at two referral andrology centers. Male patients aged 18 and over with active-stage PD, one penile plaque ≤20 mm, penile deviation ≤60°, and associated erectile dysfunction (ED). Exclusion Criteria: Multiple plaques, prior penile surgery, chronic PD stage, low testosterone, and other conditions. Data collected included age, previous treatments, comorbidities, plaque size and location, disease duration, penile curvature, ED severity (using the International Index of Erectile Function, IIEF-5), and pain during erection (using the Visual Analog Scale, VAS). Treatment Protocols The study included 445 patients divided into four groups: Group 1 (G1): 117 patients treated with Tadalafil 5 mg daily for 3 months. Group 2 (G2): 106 patients received weekly Verapamil injections plus Tadalafil 5 mg daily for 3 months. Group 3 (G3): 124 patients underwent ESWT with incremental energy levels plus Tadalafil 5 mg daily for 3 months. Group 4 (G4): 98 patients used a VED twice daily for 10 minutes plus Tadalafil 5 mg daily for 3 months. Baseline characteristics showed no significant differences except for higher ED presence in G3. Results Side Effects: Some patients experienced mild side effects from Tadalafil. A few patients in G2 and G3 developed superficial hematomas, but no major adverse events were reported. Treatment Outcomes: G3 (ESWT) showed a significant reduction in penile curvature from an average of 32.54° at baseline to 19.36° after one year. Pain during erection resolved completely in 75% of G3 (ESWT) patients. No significant differences in plaque sizes were observed at 3 months, but improvements were noted in G3 (ESWT) and G4 (VED) at one year. G4 (VED) showed significant improvement in IIEF-5 scores for ED. Discussion PD’s pathophysiology is not fully understood, complicating treatment. The disease presents with penile curvature, pain, and ED. Non-surgical treatments aim to resolve pain, prevent further curvature, and improve erectile function. Tadalafil and other PDE5is have shown antifibrotic effects in animal models and are used to improve erectile function in PD patients. Despite their use, evidence of their effectiveness in reducing symptoms is limited. Combining treatments like Verapamil injections and ESWT with Tadalafil appears logical, though high-quality evidence supporting this approach is lacking. Here ESWT has the significant advantage of non-ivasiveness Study Limitations The study’s nonrandomized, retrospective design and small sample size limit its conclusions. Future multicenter studies are needed for validation. Conclusions The study suggests that PDE5is, particularly when used in combination with other therapies, can benefit patients during the acute stage of PD by improving sexual function, reducing penile curvature, and decreasing plaque size. Multimodal therapy shows promise for long-term improvement in PD symptoms and quality of life. This represents a complete change of mind-set in the management of the acute phase of Peyronie`s disease. Whereas, initially we have waited until the acute phase became chronic, knowing about the limited effect of the drugs used previously (i.e. Potaba, Vitamin E), we now treat the acute phase effectively, i.e. by combining the antifibrotic effect of Taldalafil with the anti-inflammatory effect and stimulation of stem cells by mechano-transduction. Unfortunately, this study is only retrospective, however, it provides important information for the design of future studies. Jens Rassweiler

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