Penile Rehabilitation after

1
Penile Rehabilitation after Radical
Prostatectomy CPCN 2008
Larry Goldenberg, OBC, MD, FRCSC, FACS,
FCAHS Chairman, Department of Urologic
Sciences University of British Columbia,
Vancouver, Canada
2
Background

• Radical prostatectomy is the gold standard
  therapy for clinically localised prostate cancer
  in men with a life expectancy 10 years
• Varying degrees of Erectile dysfunction (ED) and
  urinary incontinence are both common in men
  following bilateral nerve-sparing radical
  prostatectomy (NSRP) surgery
• Maximum recovery of erectile function may take up
  to 4 years after bilateral NSRP

3
Bladder Nerves Prostate Sphincter
4

• The original
• description of NVB
• anatomy Walsh
• Donker 82
• (foetal dissection)
• Lepor 85
• (1 adult cadaver)
• enabled a more
• precise RRP

5
Post-surgical ED Mechanisms

• Nerves
• Degree/type of trauma required for neurapraxia?
• Anatomic vs functional integrity
• Neural trauma leads to structural changes in
  erectile tissue
• Denervation apoptosis
• Arteries
• Arterial injury (accessory pudendal arteries)
• Veins
• Cavernosal hypoxia-induced fibrosis with venous
  leak
• Psychologic
• Impact of cancer diagnosis on erectile function
• Impact of anxiety centered on re-initiation of
  intimacy

Mulhall JP, et al. Int J Impot Res. 1996891-94.
Rodriguez-Vela L. Actas Urol Esp.
199721909-921. Aboseif S. Br J Urol.
19947375-82. User H, et al. J Urol.
2001165531-533.
6
Post-Radical Prostatectomy Sexual Dysfunctions

• Erectile dysfunction (ED)
• Anejaculation
• Anorgasmia
• Dysorgasmia (painful ejaculation)
• Orgasm associated urine leak (climacturia)
• Penile length alterations
• Penile curvature

7
Sexual activity post-surgery

• Most patients wait until 6 weeks post-surgery to
  resume sexual activity
• Some patients resume sexual activity earlier if
  continent
• Pain is commonly associated with early resumption
  of sexual activity
• Many men can achieve orgasm without an erection

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What is the REAL incidence of ED post-bilateral
nerve sparing prostatectomy?
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ED PostRPAUA GUIDELINE REVIEW (BURNETT, AL, et
al) 31 PAPERS, MINIMAL 50 PTS
10
ED PostXRTAUA GUIDELINE REVIEW (BURNETT, AL, et
al) 31 PAPERS, MINIMAL 50 PTS
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ED PostIRAUA GUIDELINE REVIEW (BURNETT, AL, et
al) 31 PAPERS, MINIMAL 50 PTS
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Potency Recovery after Surgery
51
Maximal recovery after bilateral NSRRP may take
up to 4 years
10
Rabbani et al., AUA 2004
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Risk Factors of Post-Prostatectomy ED Patient
Factors

• Age more than 60 years
• Vascular diseases
• Diabetes
• High lipids
• Smoking
• High stage of disease
• Non-motivated partner
• PDE5-I user
• Obesity

• Assessment of a patients preoperative erectile
  function is essential.
• playing the piano

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Recovery of Erections According to Preoperative
Sexual Functioning
Rabbani F, et al. J Urol. 20001641929-1934.
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Can we really rehabilitate a penis?

• Penile rehabilitation is performed with the aim
  of achieving better and/or earlier spontaneous
  erectile recovery by
• Preservation of penile smooth muscle
• Preservation of endothelial function
• Optimization of cavernous nerve recovery

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Penile Rehabilitation?

• After radical prostatectomy, there is neural and
  vascular damage
• Decreased oxygenation of the penis, loss of
  nightime erections .ischemia
• By using ED therapy, you stimulate circulation of
  blood which protects the integrity of smooth
  muscle, nervous tissue and blood vessel linings

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Cavernosal Oxygenation
Flaccid
Erect
Flaccid pO2 35 mm Hg Increased TGF
secretion Collagen production
Penile erection pO2 gt 70 mm Hg Increased PGE
secretion Decreased collagen production
PGEprostaglandin E. TGFtransforming growth
factor.
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Alprostadil Injection study
Montorsi et al., J Urol 1997 158 1408-1410

• 30 patients randomized
• Group 1(n15) alprostadil injections 3
  times/week for 12 weeks
• Group 2 (n15) observation without erectaids
• Patient-reported recovery of spontaneous
  erections
• sufficient for satisfactory sexual intercourse

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Alprostadil InjectionsResults
n15
n12
plt0.01
Montorsi et al., J Urol 1997 158 1408-1410
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Nightly Post-Operative Sildenafil Dramatically
Improves the Return of Spontaneous Erections
Following a Bilateral NS-RRP
Padma-Nathan H, McCullough A, Giuliano F, et al.
AUA 2003, Chicago
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Prevention Study Design
Padma-Nathan H, McCullough A, Giuliano F, et al.
AUA 2003, Chicago
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Responders
P0.0156

• Responders were defined as those having a
  combined score of ?8 for IIEF Q3/4 and a
  positive response to GEQ (Over the past 4 wks,
  have your erections been good enough for
  satisfactory sexual activity

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Improvement in recovery of erectile function
following treatment with nightly Sildenafil 25 mg
in men post-NSRP
43 patients 95 had nocturnal erections 2 weeks
after surgery
25
20
15
IIEF-5-score
10
5
0
Pre-op
6
12
24
36
52
Weeks after surgery
plt0.001
Bannowsky et al. BJU Int 2008 101 127983.
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Potency rate following treatment with nightly
sildenafil 25 mg (1 year) followed by Sildenafil
on-demand
Patients able to achieve and maintain an erection
long enough for successful intercourse
Yes ()
Control group n20
Sildenafil n23
Control group took no medication before the
on-demand period
Bannowsky et al. BJU Int 2008 101 127983.
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Limitations of existing studies

• Padma-Nathan et al. 2003
• Small sample size (N76)
• Single centre
• Did not compare nightly dosing with on-demand use
  of a PDE-5 inhibitor
• Bannowsky et al. 2008
• Small sample size (N43)
• Single centre of surgical excellence does not
  reflect general worldwide urological practice
• Not placebo-controlled
• 95 of patients had nocturnal erections following
  catheter removal not typical of post-surgical
  situation in general urological practice

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Postop Rehab Questions Remain

• When do you start?
• Do other PDE5 inhibitors work?
• How long do you need to treat for?
• Daily vs. PRN?
• Do you have to have N function for rehab to work?
• Will rehab salvage those with pre-existing ED?
• What is the age cutoff for rehab efficacy?

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Recovery of erections intervention with
Vardenafil early nightly therapy (REINVENT)
study design
Randomized, double-blind, double-dummy,
multicentre, parallel-group comparison of
vardenafil nightly or on-demand vs placebo in men
immediately (within 14 days) following bilateral
NSRP
Double-blind
Single-blind
Open-label
Nightly1
Random-isation
Surgery
Placebo
Vardenafil on-demand
On-demand2
Screening
Placebo3
1 month
14days
9months
2 months
2 months
1) 10 mg nightly vardenafil (which could be
decreased to 5 mg if required) plus on-demand
placebo 2) flexible-dose on-demand vardenafil
(starting at 10 mg with option to titrate to 5 mg
or 20 mg) plus nightly placebo 3) nightly
placebo plus on-demand placebo
Montorsi et al. Eur Urol 2008 in press.
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REINVENT Centers and Countries
Montorsi et al. Eur Urol 2008 in press.
number of patients enrolled
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REINVENT IIEF-EF domain score 22 (mild ED) over
9 months of treatment
Placebo
Vardenafil nightly

Vardenafil on-demand


Estimated rate ()


3 months
6 months
9 months
p0.0144 for comparison of vardenafil nightly vs
placebo p0.0001 for comparison of vardenafil
on-demand vs placebo plt0.01 for comparison of
vardenafil on-demand vs nightly (For all
secondary variables, plt0.05 considered to be
nominally significant)
mITT population
Montorsi et al. Eur Urol 2008 in press.
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REINVENT IIEF-EF domain score 26 (normal EF)
over 9 months of treatment
Placebo
Vardenafil nightly
Vardenafil on-demand
Mean per-patient success rates ()

n143
n149
n152
plt0.0003 for the comparison of on-demand vs
placebo p0.479 for the comparison of nightly vs
placebo
Observed at last observation carried forward
(LOCF)
mITT population
Montorsi et al. Eur Urol 2008 in press.
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REINVENT conclusions

• The best-designed study to date investigating
  PDE-5 inhibitor therapy for recovery of erectile
  function in men following bilateral nerve-sparing
  radical retropubic prostatectomy (NSRP)
• Rigorous in design and blinding
• Large study sample
• Designed to reflect real-life population of
  patients undergoing bilateral NSRP surgery

Montorsi et al. Eur Urol 2008 in press.
32
REINVENT conclusions (2)

• In this study, the primary efficacy variable was
  not met
• After 9 months of treatment plus 2 months of
  washout, nightly dosing with vardenafil did not
  show any effect beyond that of on-demand use on
  recovery of erectile function.
• Vardenafil on-demand showed good efficacy in this
  notoriously difficult-to-treat patient population
  with ED.
• Vardenafil on-demand was observed to work early
  after NSRP.
• These findings support a shift towards on-demand
  dosing with PDE-5 inhibitors for the treatment
  of ED in men post-prostatectomy.

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Maximizing the effect of PDE5s

• Why patient wants them
• How theyll be used
• What they wont do realistic expectations
• Discuss with partner
• Practice via masturbation
• Use first in outercourse
• Combining w/other treatments aids
• Conditions partners conditions
• Unanticipated consequences

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How Aging Can Change Sexuality

• Desire
• Erection
• Ejaculation
• Orgasm
• Refractory period
• health partner availability are factors.

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Hold on, Im gonna call Tech Support.
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How Sexuality Can Remain Stable With Age

• Desire for closeness
• Desire to be desired
• Desire to feel good in body
• Sense of humor
• Experience of orgasm

• Desire
• Fantasy
• Preference
• Masturbation
• Satisfaction

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The male brings more than his body into the
doctors office

• his relationship(s)
• his past
• his feelings
• his libido
• his sexual function
• his performance anxiety
• his fear of aging
• his partner's concerns
• cultural media messages

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Common assumptions about older males sexuality

• Theyre not sexual
• Theyre monogamous
• They do only vanilla sex
• Theyre sexual only with women
• Erectile function is a central issue in sexual
  function

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Assumptions/beliefs of men
t,,, (and men),, and.

• stereotypes about women (and men)
• how his body should function
• normal sexual activities preferences
• the meaning of sexual difficulties
• beliefs and (mis)information about aging
• religious and cultural concerns
• beliefs about medical treatment

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To deal with the complete man--his body,
lifestyle, assumptions, aging,
sexuality--requires a group of health care
professionals working as a team.
Professionals often share many of these
assumptions,undermining good care.
Anything less, and were just dealing with
patients -- not people.