function. The most commonly used therapy was

injection based, perhaps suggesting that other

effective modalities for post-RP therapy would shift

this dynamic. Physicians familiar with sexual

medicine as a discipline are more likely to imple-

ment post-RP therapy targeted at preservation of

erectile function, supporting the role for increased

awareness of this concept.

Given the impact of RP on erectile function, it is

prudent for physicians to implement strategies

related to minimizing and reversing post-RP ED.

This requires both a thorough understanding of the

pathogenesis of post-RP ED and the role of various

therapies to mechanistically impact the process.

Clinically, physicians require treatment strategies

and assessment tools to capture response and

satisfaction.

This

review

article

attempts

synthesize the literature on the various modalities

of post-RP therapy targeted for recovery of erectile

function. We discuss the clinical strategies designed

to overcome the non-surgical factors believed to

precipitate the development of post-RP ED. Addi-

tionally, we present some commonly used validated

instruments that are useful to define baseline

erectile function and follow response to therapy.

Physiologic mechanism of post-RP ED

RP is believed to impact long-term erectile function

by interfering with the neurological mechanisms

that facilitate cavernosal oxygenation. While the

mechanism of such neurological disruption or

trauma (neuropraxis) is not entirely clear, hypoth-

eses include direct trauma during surgery (for

example retraction injury), damage from tissue

electrocautery, disruption of the neural vasculature

and generalized local inflammation associated with

the procedure.

Regardless of the etiology of this

neurological damage, the functional consequences

of impaired parasympathetic penile function man-

ifest themselves as ED.

This neuropraxia results in a post-procedural ED

with associated cavernosal hypoxia.

Whereas this

issue underlies early post-operative ED, fibrosis

ensues and is marked by the presence of transform-

ing growth factor

, a marker of chronic inflamma-

tion and fibrosis.

12,13

Additionally, anti-fibrotic

mediators such as prostaglandin E1 (PGE1) and

cyclic adenosine monophosphate are under-repre-

sented during this process. Therefore, while neuro-

praxia

may

reversible,

penile

fibrosis

permanently damages cavernosal function and pro-

duces chronic ED. Furthermore, this destructive

cycle leads to cavernosal smooth muscle apop-

tosis.

In response to these hypoxic conditions,

the tissues upregulate the nitric oxide pathway,

mediated by inducible nitric oxide synthase and

cyclic guanosine monophosphate to attempt to

improve penile blood flow.

Clinically, the impact of this chronic inflamma-

tory response to cavernosal hypoxia is manifested by

long-term collagen deposition and reduced smooth

muscle.

In addition to vaso-occlusive disease,

venous leak develops due to the reduction in

corporal elasticity. Over time, these patients present

with increasing rates of ED. Therefore, while

occasional use erectogenic pharmacotherapy will

likely produce a transient erection, especially early

after surgery, there is long-term deterioration of

the normal physiologic processes involved in this

process.

This broad overview of mechanisms predisposing

post-RP patients to ED suggests multiple points of

intervention to prevent the development of ED in

these patients. Most importantly, tissue oxygenation

may reduce the prevalence of chronic inflammation

and cavernosal fibrosis. Interestingly, hyperbaric

oxygen therapy in an animal model of cavernous

nerve injury has not been shown to significantly

reverse or minimize this process, suggesting that

there are multiple mechanisms involved.

Secon-

darily, cytokine mediators of tissue fibrosis and

inflammation are targets for pharmacotherapy aimed

at preserving cavernosal tissue integrity. The con-

cept of erectile preservation (EP) is premised on

minimizing the factors that impair long-term erectile

function. Therefore, therapeutic strategies must

target the aforementioned mechanisms to provide

patients with optimal functional outcomes.

Rationale for erectogenic

pharmacotherapy in RP patients

Terminology

The use of erectogenic agents after prostatectomy

has traditionally been referred to as penile rehabi-

litation. However, rehabilitation implies the reversal

of functional deterioration. In contrast, the objective

in patients with a planned RP is the preservation of

pre-operative erectile function. In fact, several

programs that initiate the use of erectogenic phar-

macotherapy in this patient population begin in the

weeks before surgery.

For this reason, the program

is referred to as EP rather than penile rehabilitation.

Perhaps, these terms are similar in their intent but

the term ‘EP’ suggests the desired outcome to

patients (for example a short-term therapeutic bridge

directed toward the recovery of natural erections)

and the urologic team to promote awareness and

compliance. Additionally, the protocol allows pa-

tients to have medication-assisted erections regard-

less of natural erectile capacity, thus preserving

erectile function throughout their recovery.

Phosphodiesterase-5 inhibitors

The use of phosphodiesterase-5 (PDE-5) inhibitors

is, in general, the most common therapy offered to

Review and treatment protocol: erectile preservation for RP patients

DJ Moskovic

et al

182

International Journal of Impotence Research