patients after prostatectomy.

8,9

The value added by

offering PDE-5 inhibitors to post-RP patients is

twofold: it supports a patients’ ability to achieve

an erection after surgery and contributes to the long-

term recovery of erectile function. While the former

property of PDE-5 inhibitors has been clearly

established, the latter has only begun to be eluci-

dated. This review will summarize the compelling

evidence to support PDE-5 inhibitors for both these

objectives, making it the cornerstone of our EP

program.

Several

studies

have examined daily

PDE-5

inhibitor therapy for post-RP patients. McCullough

et al.

demonstrated the return of normal nocturnal

penile tumescence and unassisted erectile function

in patients who were treated with nightly sildenafil

after RP. For the sildenafil group of patients, there

was a dose-dependant improvement in recovery of

nocturnal penile rigidity. Importantly, the larger trial

from which this subgroup analysis is based suggests

that this outcome in fact correlates with the recovery

of natural erectile function (see below).

18,19

Addi-

tionally, there was a substantial difference in the

rate of recovery of erections satisfactory for sexual

intercourse (for example a rate of 5

–7

) for

patients taking 50–100 mg of sildenafil nightly.

However, the study was very small (

54) and

represents a subgroup analysis of a larger trial. The

authors remark that, since only one patient in the

placebo recovered nocturnal erectile function, the

small sample size limits comparisons between

groups. However, the consistent performance of

the two sildenafil groups versus the control supports

this therapeutic strategy in this patient population.

In a complementary study, Bannowsky

et al.

reported the impact of nightly sildenafil on the

progression of international index of erectile func-

tion (IIEF) scores after RP. In this small controlled

study, patients were randomized based on pre-RP

IIEF scores, nocturnal erectile function, age and NS

status. After surgery, patients experienced a decline

in IIEF scores of over 75% on average at the 6-week

assessment. Steady increases in IIEF scores were

observed in both groups thereafter, with a statisti-

cally significant increases in IIEF scores observed at

36 and 52 weeks for PDE-5 inhibitor patients over

control. The fact that a small study was able to show

a statistically significant difference in outcomes

suggests that the effect of sildenafil on sexual health

is very favorable. However, a larger study would

improve confidence in these results.

Definitive evidence to support use of nightly PDE-

5 inhibitor therapy has been derived from the above-

referenced randomized, placebo-controlled trial by

Padma-Nathan

et al

In the study, the authors

compared natural erectile function after an 8-week

washout period subsequent to 36 weeks of nightly

sildenafil therapy. Patients reported a return of

normal ‘spontaneous’ erections at a 7

rate over

control patients (4% versus 27%) based on IIEF

scores (for questions 3 and 4)

8 when also

responding positively to the question ‘were erec-

tions good enough for satisfactory sexual activity?’.

In general, IIEF scores for the sildenafil patients

were just below 50% greater than placebo patients

(13.1 versus 8.8). Interestingly, the rate of recovery

for patients in the control arm was surprisingly

low and the authors were unable to clearly explain

why. Irrespective of this absolute observation, the

relative performance of the study group is very

impressive and compelling. Of note, the doses of

sildenafil were between 50 and 100 mg over the

course of therapy.

Montrosi and McCullough

performed a compre-

hensive and elegant meta-analysis examining the

role of PDE-5 inhibitor therapy after surgery. The

authors reviewed studies of post-RP patients, where

PDE-5 inhibitor therapy was an independent vari-

able in the analysis. Pooling all results together

yielded an overall response rate of 35% with

considerable variability (95% confidence interval:

24–48%). Noting that these data include patients

sustaining varying degrees of NS during their

surgery, the authors independently assessed this

factor to describe responses to PDE-5 inhibitor

therapy. The authors noted NS to be a very

important factor in segmentation, where patients

undergoing NS RP had a response rate ranging from

35 to 75% and patients whose surgery was non-NS

ranged from 0 to 15%. The combined odds ratio for

this result was determined to be 12.1. Careful

analysis of the degree of NS demonstrated statisti-

cally comparable rates of response between uni-

lateral and bilateral NS, but the range of outcomes

was more variable in the unilateral NS group

compared with the bilateral NS group. While this

study demonstrates the remarkable effectiveness of

PDE-5 inhibitors after RP, particularly in patients

who undergo NS surgery, there are some important

weaknesses inherent in the studies comprising this

meta-analysis. Only seven studies were included in

the primary response analysis and only five of those

commented on NS. More so, the authors’ ability to

distinguish between the extent of NS relied on only

four studies. As is a common problem in this body of

literature, the results of the study would be more

compelling if a standard measure of erectile func-

tion was included in all studies. Regardless, this

study was successful in definitively establishing the

value of PDE-5 inhibitors for post-RP patients.

Perhaps, the least established concept is the idea

that pre-RP PDE-5 inhibitor therapy adds value to

EP. While no formal published data are available,

some have described improvement in recovery of

post-operative erectile function in animal models

when PDE-5 inhibitors are used before injury.

Interestingly, the value of a formal EP program

versus on-demand dose PDE-5 inhibitor therapy has

not been definitively elucidated. Whereas the above-

referenced studies rely on some regularity in dosing

Review and treatment protocol: erectile preservation for RP patients

DJ Moskovic

et al

183

International Journal of Impotence Research