Update on Penile Rehabilitation

Justin Parker, MDAssistant Professor of UrologyUniversity of South FloridaJames A. Haley VA Medical Center

Disclosure

I am a consultant/speaker for Coloplast but have no conflicts regarding this presentation.

Objectives

Discuss the pathophysiology of post prostatectomy erectile dysfunction Understand the limitations of the data

supporting penile rehabilitation protocols Consider possible rehab protocols which

may be utilized in a typical clinical practice

Erectile dysfunction after prostatectomy

Wide range of reported potency rates after radical prostatectomy– Review of RRP series from 1990-2005 with

minimum 12 month followup: 31-86%– Nerve sparing laparoscopic radical

prostatectomy: 42-76%

Dubbelman et al. Sexual function before and after radical retropubic prostatectomy: a systematic review of prognostic indicators for a successful outcome. Eur Urol 2006;50:711–20.

Ficarra et al. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol 2009;55:1037–63.

Robotic prostatectomy and ED

Previously published surgical series showed 12 month potency rates of 70-80%

Ficarra et al. 2012– Systematic review and meta-analysis– 12 month potency rates: 54-90%– 24 month potency rates: 63-94%

4th ICSM 2015 – Insufficient evidence that a specific surgical technique open vs

laparoscopic vs robot-assisted promotes better results for postoperative EF recovery

– Predictors of erectile recovery include but not limited to younger age, preoperative function, and bilateral nerve sparing status

Ficarra et al. Eur Urol 2009;55:1037–63.Ficarra et al. Eur Urol 2012;62:418-430.Salonia et al. J Sex Med 2017; 14;285-296.

Pathophysiology of post prostatectomy ED Course of cavernous nerves more complex than

previously thought– Incomplete nerve sparing- obvious cause

Complete nerve sparing– Nerves likely still affected by direct trauma, stretching,

heating, ischemia, and local inflammation– Temporary neuropraxia

Penile oxygenation

Oxygen tension in normal flaccid penis– 25-43 mmHg

Oxygen tension in normal erect state– 100 mmHg

Temporary neuropraxia– Lack of normal erection cycle– Penile tissue in a constant state of low oxygen supply

due to loss of nocturnal erections– May lead to apoptosis and fibrosis

Penile alterations after nerve injury

Hypoxia results in fibrosis and up-regulation of collagen production

Fibrosis results in veno-occlusive dysfunction and loss of penile length

Fibrosis may be down-regulated with improved oxygenation

Leungwattanakij et al. J Androl, 2003Shaiji et al. Can Uro Assoc J, 2009Mulhall et al. J Sex Med, 2007

Venous leakage

Venous leakage is present:– 14% at 4 months from surgery– 35% at 8 to 12 months from surgery– 50% after 12 months from surgery

Prognosis for return of functional erections is worse when venous leakage is present

Mulhall et al. Journal of Urology, 2002

Concept of penile rehab

Improve cavernosal oxygenation Preserve smooth muscle and prevent fibrosis Preserve endothelial function Improve return of spontaneous erections

Rehabilitation regimens may consist of:– PDE5 inhibitors– Intracavernosal injection– MUSE– Vacuum erection devices

Mulhall et al. J Sex Med, 2007

To rehab or not to rehab?- Practice patterns Teloken et al. J Sex Med 2009

– Web based survey among members of the ISSM– 301 physicians responded– 87% performed some form of penile rehab– Of those who did not suggest or prescribe penile

rehab, primary reason was excessive cost (50%)

But what is the evidence?– 25% of those who do not perform penile rehab stated it

was due to lack of evidence

Alprostadil intracavernosal injection

Montorsi et al: ICI therapy 3x/week– 67% of patients with spontaneous erections– 20% of controls spontaneous erections

Mulhall et al: either sildenafil, or ICI if non-responsive to sildenafil– 52% of rehab patients with improved natural erections

vs 19% of non-rehab– Improved response to sildenafil and ICI in rehab group

Further literature is scarce with major limitations

Montorsi et al. J Urol, 1997Mulhall et al. J Sex Med, 2005

MUSE

Intraurethral alprostadil suppository Raina et al- men received 125 or 250 μg three

times per week vs no ED treatment– 74% in treatment group regained erections satisfactory

for intercourse vs. 37% in the control group– Patients allocated to groups by choice

McCullough et al- 139 men randomized to nightly MUSE or sildenafil– No significant difference between the two group at 1

year– Loss of penile length noted in both groups

Phosphodiesterase Inhibitors

Preclinical animal data showed benefit of PDE5 inhibitors – Decrease erectile tissue fibrosis– Prevent degeneration of nerves– Stimulate neuro-regeneration

Several human trials were performed with contradictory results

Phosphodiesterase inhibitors-conflicting data Padma-Nathan et al.

– 76 patients randomized to nightly sildenafil vs. placebo for 36 weeks

– Spontaneous erectile function good enough for intercourse in 27% vs 4% in the placebo group

– Improved nocturnal erections in the sildenafil group

Montorsi et al.– Double blind RCT evaluating nightly vardenafil vs. on demand– On demand dosing was associated with higher IIEF scores– Unassisted erectile function was not significantly improved for

either group

Phosphodiesterase inhibitors

Data is contradictory Medication is relatively safe

– Well known side effects and comfortable to urologists Current evidence fails to clearly demonstrate

improvement in spontaneous, unassisted erections– But may be better than doing nothing

Cost remains a significant barrier to routine use for many

VED

Preclinical studies– Transient increase in arterial flow and

oxygenation to the corpora cavernosa– Preservation of endothelial and smooth muscle

integrity– With constriction band oxygen saturation drops

• Do not use band in rehab setting

Post- prostatectomy studies– Controversial results

VED

Kohler et al- randomized study of early intervention with VED compared with no treatment after prostatectomy– Higher IIEF scores at 3 and 6 months in VED group

Raina et al- randomized 109 patients to daily VED or no treatment– No significant difference in erectile function– 63% in the no treatment group noted decrease in

penile size vs. only 23% in the VED group

VED combined with PDE5 inhibitors

Basal et al- PDE5’s alone or in combination with VED – Significantly improved postoperative erectile function

recovery but not VED alone Engel- randomized pilot of tadalafil 20mg three

times weekly or tadalafil plus VED– Higher IIEF score in the combination group at 6, 9, and

12 months

VED and penile length

Dalkin and Christopher– Daily use of VED begun day after catheter removal

and continued for 90 days– 39 patients– VED use >50% of days- 1/36 had decrease of

stretched penile length >1cm– VED use <50% of days- 2/3 had decrease of length

>1cm Kohler study

– Stretched penile length was preserved in the VED group compared to no treatment

Penile Rehab- USF protocol

Initiate as early as possible after catheter removal VED- recommend using at least 3-5 times per

week without a constriction band – Cycle intermittently over about 5-10 minutes

Daily or every other day PDE5– 5mg tadalafil or 25mg sildenafil (also consider 20mg

generic Revatio)– If cost an issue then QOD

Initiate ICI for on demand use as soon as patient is ready to resume sexual activity

Penile rehabilitation summary

Overall concept is to maximize tissue oxygenation and prevent fibrosis during period of neuropraxia– Timing is likely important- start as soon as possible to

minimize fibrosis The available data is inadequate to support one

particular protocol over another Makes sense to combine pharmacological and

mechanical methods Helps to make the patient an active participant in

their recovery