(for example nightly, four time per week and so on),

a study by Montorsi

et al.

was unable to demon-

strate a difference in functional outcomes between

patients on demand-dose PDE-5 inhibitors versus a

formal EP program schedule in a three-arm con-

trolled study. However, this study neither assessed a

comprehensive EP program nor did it document

compliance with regular PDE-5 inhibitor dosing.

Additionally, it was composed of numerous treat-

ment sites and did not control for surgeon skill

in preserving the cavernosal nerves. Thus, this

outcome cannot be extrapolated to all formal

EP regimens. Despite the statistical equivalence

between these two groups, each showed a dramatic

improvement in erectile function compared with

the control group.

The

pathophysiologic

modification

PDE-5

inhibitors can also be observed histologically.

Mulhall

et al

observed the role of sildenafil in

preservation of erectile function after cavernous

nerve crush injury. In a rat model for cavernosal

nerve injury, the authors demonstrated maintenance

of cavernosal smooth muscle integrity and observed

a trend in favor of improved erectile function

outcomes. The authors attribute this to improved

penile hemodynamics immediately after injury, thus

preventing smooth muscle apoptosis with perma-

nent damage to the tissues. Schwartz

et al.

demonstrated the dose-dependant impact of silde-

nafil on corporal smooth muscle after RP. In this

study, two groups (50 and 100 mg of sildenafil every

other night) were biopsied at the time of RP and 6

months post-operatively. While their small study

(

21) lacks a control group because of concern for

the psychological trauma associated with the 6-

month post-RP biopsy, the patients in the 50-mg

group maintained pre-RP corporal smooth muscle

levels, whereas the patients in the 100-mg actually

had a significant increase in post-RP corporal

smooth muscle (as a percent of the histologic section

assessed by a computer-based analysis tool). At 6

months, the overall prevalence of veno-occlusive

disease in both groups was

5% (one patient). The

authors comment on other reports of the chronology

of post-RP veno-occlusive disease where evidence of

disease is present in at least 50% of post-RP

impotent patients, if not all post-RP patients, at

approximately 6 months.

25,26

Furthermore, a study

by Mulhall

et al.

suggested that rates of veno-

occlusive disease increased through 18 months

from 14 to 50% post-RP. Vascular status was also

predictive of the likelihood the patient had recov-

ered erectile function sufficient for sexual activity;

47% of men with normal penile vascular status had

recovered erections, while only 8% of patients with

venous leak reported sufficient erectile function

after 1 year post-RP. These two studies offer insight

into the pathophysiology of post-RP ED and suggest

that EP may offset some of the detrimental effects of

the procedure.

For this reason, PDE-5 inhibitor therapy is the

backbone of our institution’s EP program. Pharma-

cotherapy with PDE-5 inhibitors is initiated prior to

surgery given the aforementioned anecdotal reports

and, consistent with many of the case series and

trials reported herein, is continued throughout the

duration of recovery. Low-dose PDE-5 inhibitor

therapy (25 mg) is utilized given the multiple

modality approach that is described below.

Intrauretheral alprostadil suppositories

Alprostadil, a PGE1 analog, is administered to

patients to increase corporal oxygenation by pro-

moting blood flow. This drug is not only most

commonly administered through intracavernosal

injection (ICI), but is also available in the form of

an intrauretheral suppository (MUSE

, Vivus Inc.,

Mountain View, CA, USA). Montorsi

et al.

re-

ported that recovery of spontaneous erections was

250% more likely for a patient receiving alprostadil

ICI compared with an untreated control. Thus, the

concept of localized (for example non-systemic)

penile therapy demonstrated dramatic efficacy with-

out concern for the systemic consequences of oral

pharmaceuticals.

The use of intrauretheral alprostadil suppository

therapy was documented in 1997, although early

results were inconsistent and not reproducible.

28,29

Raina

et al.

were the first to demonstrate the long-

term effectiveness of this type of therapy in post-RP

patients. Their analysis consisted of a retrospective

review of post-RP patients 6 months after surgery

who subjectively reported ED (defined as the

inability to achieve vaginal penetration). Patients

were told to use MUSE (titrated up to 1000

g based

on efficacy) on demand. Overall, 55% were able to

achieve erections sufficient for penetration with

61% of partners reporting satisfaction with this

modality of therapy. Sexual health inventory in men

(SHIM) scores after MUSE use were comparable

with pre-RP scores in these patients.

McCullough

et al.

adapted the concept of

nightly low-dose PDE-5 inhibitor therapy to com-

pare the effectiveness of this commonly used

approach with nightly MUSE. Patients were rando-

mized into groups using nightly sildenafil or MUSE

(125

g titrated to 250

g within 1 month if toler-

able). The study included only men with IIEF scores

of at least 26. Treatment was initiated upon catheter

removal and was continued for 9 months. After a

1-month washout

period where

patients were

instructed to attempt sexual intercourse without

medication to assist with erections, demand-dose

erectogenic

aids

(sildenafil)

were

provided

patients. The final assessment was conducted

11 months after initiating the protocol. IIEF score

rose sequentially and were approximately 50–75%

higher after treatment than at baseline. Intercourse

success rates nearly doubled from the 3 months visit

Review and treatment protocol: erectile preservation for RP patients

DJ Moskovic

et al

184

International Journal of Impotence Research