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Penile re-modeling in Peyronie’s disease: Bend the Curve

04_Pramod Pic Chicago

Andrology Division, Dept of Urology,
NU Hospitals & NU Fertility, Bangalore, India.
Pramod23dr@gmail.com

06_Manfredi

University of Campania “Luigi Vanvitelli” – Naples, Italy.
manfredi.celeste@gmail.com

Peyronie’s disease (PD) can cause significant physical and psychological impact on the quality of life by causing erectile dysfunction and penile curvature. The exact etiology of PD is still unknown, but most agree that repetitive microtrauma to penile tunica albuginea leads to this collagen disorder. Penile curvature could be ventral, dorsal, lateral, combined, or hourglass deformity. The management of penile curvature alone in the absence of erectile dysfunction in PD gets tricky.

A substantial number of men (21-46%) notice significant reduction in erectile function after plaque incision/excision and grafting without a penile prosthesis in PD [1-2]. Hence one should explore all possible remodeling options to correct penile curvature without incising/excising the plaque. Traditionally most interventions to correct penile curvature were limited to the chronic phase of PD, but there has been a recent shift in targeting the disease as early as in the acute phase [3-4]. Penile re-modeling (without incising /excising the penile plaque) can be done with or without assisted devices during different stages of management of PD.

Various penile re-modeling strategies include vacuum device (VD), penile traction device (PTD), intralesional Collagenase Clostridium histolyticum (CCH) injection, manual modeling over a penile prosthesis intra-operatively, modeling at home over a penile prosthesis and combined modeling (combination).

For the ease of understanding, the modeling procedures can be sub-grouped into three sections: non-surgical, intra-operative and post-operative.

1. Non-Surgical:

  1. Collagenase Clostridium histolyticum (CCH) injection & modeling,
  2. Vacuum device (VD)
  3. Penile traction device (PTD)

CCH & Modeling:

The IMPRESS (Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of CCH intralesional injections in subjects with PD [5]. IMPRESS regimen consisted of 4 cycles. One cycle involved 2 CCH injections given 1-3 days apart, followed by modeling first done by healthcare worker and subsequently by the patient for 6 weeks at home. Modeling technique involved applying pressure for 30 seconds to stretch the penis in opposite direction of curvature keeping plaque as the fulcrum. A post-hoc meta-analysis of IMPRESS I and II data reported that the CCH group noted 34% improvement (mean -17.0±14.8° change per subject) in mean penile curvature compared with a mean 18.2% improvement in placebo-treated subjects. Three cases of corporal rupture (serous adverse event) were repaired subsequently.

There have been no published results of CCH in PD from Asian countries probably due to higher cost, lack of insurance coverage or more importantly non-availability of CCH in Asian countries. European urologists were in for a surprise shock about discontinuation of CCH in Europe in November 2019 [6]. Currently the CCH is restricted to USA alone.

Vacuum device (VD):

Animal studies have shown antiapoptotic, antifibrotic, and smooth muscle preserving effects of VD [7]. The role of VD in PD is still evolving and at present the use of vacuum device has shown 5–25 degree improvement in curvature [8]. More studies are required to substantiate the role of VD in PD. 

Penile Traction Device (PTD):

PTD helps in modeling by mechanotransduction, a concept that has been borrowed from orthopaedics. The use of mechanical traction and tissue expansion therapy results in changes in connective tissue by cellular proliferation and expansion of the extracellular matrix.

PTD can be used as a monotherapy or as a combination therapy. There are various models of PTD which include Andropenis®, Andropeyronie®, FastSize Medical Extender®, Penimaster Pro® system and RestoreX®. Monotherapy with PTD has shown improvements in curvature ranging from 14-32 degrees in both acute and chronic phase of PD.

PTD combination therapy has been done either with oral therapy, intralesional therapy or surgical therapy. A significant limiting factor of PTD is the duration of application of these devices which is usually around 4-6 hours/ day except the latest RestoreX® which is applied for 60-90 minutes/day [9].

2. Operative:

The term “manual modeling” was first described by Wilson & Delk in 1994 [10]. It was an intraoperative manoeuvre after placement of penile prosthesis to correct residual curvature in PD with a reported success rate of 86 % (118/138).  Although this technique met with a storm of criticism when it was first published, it subsequently became a standard treatment protocol in most centres worldwide.

Wilson’s intra-operative manual modelling involved bending the penis in opposite direction of curvature for 90 seconds over the penile prosthesis after securing the corporotomy site and the pump tubing. Second (final) attempt may be attempted if residual curvature persists. The concern of higher device malfunction after manual modeling is still debatable.

3. Post-Operative:

The usual dictum is that residual curvature of more than 30 degree even after manual modeling over PP warrants placement of a graft.  Moncada et al published a structured home-modeling (HM) protocol in residual curvatures of up to 45 degrees to avoid additional grafting surgeries [11]. At 3 and 6 months, 85.5% and 94.7% of the patients had < 10-degree residual curvature respectively. Moncada’s HM protocol was first instructed in clinic by the urologist after 4 weeks of surgery and subsequently done by the patient himself at home. Each cycle of the protocol involved bending the penis for 30 sec in opposite direction of residual curvature after full inflation of inflatable PP and many such cycles were done in a day for a total of 6 months.

Rybak et al noted that post-operative combination therapy with PTD for 2–6 hours daily starting 3–4 weeks post-operatively had significantly greater mean increase in stretched penile length when compared to without PTD (1.48 cm vs 0.24 cm) [12].

Conclusion:

One should explore the various re-modeling options to straighten the penis in PD before attempting to incise/excise the plaque thereby preserving the native erectile and penile sensory functions of PD patients. The penile traction device is being increasingly studied since last decade and is evolving as a feasible non-operative modality with less complications. Manual modeling continues to be practised intra-operatively over penile prosthesis to correct residual curvatures. More studies are required to validate the role of vacuum device in PD. The future of collagenase injection is uncertain considering its higher costs and non-availability in most continents. 

References:

  1. Taylor FL. Predicting erectile dysfunction following surgical correction of Peyronie’s disease without inflatable penile prosthesis placement: vascular assessment and preoperative risk factors. J Sex Med. 2012 Jan;9(1):296-301.
  2. Flores S. Erectile dysfunction after plaque incision and grafting: short-term assessment of incidence and predictors. J Sex Med. 2011 Jul;8(7):2031-7.
  3. Cocci A. Efficacy of Collagenase Clostridium histolyticum (Xiapex®) in Patients with the Acute Phase of Peyronie’s Disease. Clin Drug Investig. 2020 Jun;40(6):583-588.
  4. Martínez-Salamanca JI. Acute phase Peyronie’s disease management with traction device: a nonrandomized prospective controlled trial with ultrasound correlation. J Sex Med. 2014 Feb;11(2):506-15.
  5. Gelbard M. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013 Jul;190(1):199-207.
  6. Cocci A. The End of an Era: Withdrawal of Xiapex (Clostridium histolyticum Collagenase) from the European Market. Eur Urol. 2020 May;77(5):660-661.
  7. Lin H. Effect of Penile Traction and Vacuum Erectile Device for Peyronie’s Disease in an Animal Model. J Sex Med 2017 Oct;14(10):1270-1276.
  8. Raheem AA. The role of vacuum pump therapy to mechanically straighten the penis in Peyronie’s disease. BJU Int 2010 Oct;106(8):1178-80.
  9. Joseph J. Outcomes of RestoreX Penile Traction Therapy in Men With Peyronie’s Disease: Results From Open Label and Follow-up Phases. J Sex Med. 2020 Dec;17(12):2462-2471.
  10. Wilson SK. A new treatment for Peyronie’s disease: modeling the penis over an inflatable penile prosthesis. J Urol 1994 Oct;152(4):1121-3.
  11. Moncada I. Home modeling after penile prosthesis implantation in the management of residual curvature in Peyronie’s disease. Int J Impot Res. 2020 Jul 8. doi: 10.1038/s41443-020-0325-6. Epub ahead of print. PMID: 32641777.
  12. Rybak J. A retrospective comparative study of traction therapy vs. no traction following tunica albuginea plication or partial excision and grafting for Peyronie’s disease: measured lengths and patient perceptions. J Sex Med. 2012 Sep;9(9):2396-403.