Nightly vs on‐demand sildenafil for penile rehabilitation after minimally invasive nerve‐sparing radical prostatectomy: results of a randomized double‐blind trial with placebo

Abstract

Objectives• To clarify the role of phosphodiesterase type 5 (PDE5) inhibitors in post-prostatectomy penile rehabilitation (PPPR).• To compare nightly and on-demand use of PDE5 inhibitors after nerve-sparing minimally invasive radical prostatectomy (RP). Patients and Methods• We conducted a single-institution, double-blind, randomized controlled trial of nightly vs on-demand 50-mg sildenafil citrate after nerve-sparing minimally invasive RP. • A total of 100 preoperatively potent men, aged <65 years, with scores on the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) ≥26, underwent nerve-sparing surgery.• The patients were randomized to either nightly sildenafil and on-demand placebo (nightly sildenafil group), or on-demand sildenafil and nightly placebo (on-demand sildenafil group; maximum on-demand dose six tablets/month) for 12 months. Patients then underwent a 1-month washout period. • Validated measures of erectile function (IIEF-EF score and the Expanded Prostate Cancer Index Composite [EPIC])were compared between treatment groups over the entire 13-month time course, using multivariable mixed linear regression models. Results• The treatment groups were well matched preoperatively (mean age 54.3 vs 54.6 years, baseline IIEF-EF score 29.4 vs 29.3, for the nightly vs the on-demand sildenafil groups, respectively).• No significant differences were found in erectile function between treatments (nightly vs on-demand sildenafil) at any single timepoint after RP, after adjusting for potential confounding factors.• When evaluated over all timepoints simultaneously, no significant effects of treatment group (nightly vs on-demand sildenafil) were found on recovery of potency, as assessed by absolute IIEF-EF scores (P = 0.765), on percentage of men returning to an IIEF-EF score >21 (P = 0.830), or on IIEF-EF score recovery to a percentage of baseline value (P = 0.778).• When evaluated over all timepoints simultaneously, no significant effects of treatment group were found on secondary endpoints such as assessment of potency (including EPIC item 59 response 'erections firm enough for intercourse'), attempted intercourse frequency or confidence. Conclusions• Erectile recovery up to 1 year after RP does not differ between previously potent men who use sildenafil nightly compared to on-demand. • This trial does not support chronic nightly sildenafil as being any better than on-demand sildenafil for use in penile rehabilitation after nerve-sparing minimally invasive RP.

Nightly sildenafil use after radical prostatectomy has adverse effects on urinary convalescence: Results from a randomized trial of nightly vs on-demand dosing regimens

“…Since sildenafil nightly use was not associated with a significant early or late improvement in erectile function in preoperatively potent men (the primary outcome of this RCT), 5 we feel that the present urinary outcomes data support on-demand rather than nightly/chronic use of shortacting PDE5i in such patients in the early post-prostatectomy setting. There are limitations inherent to our study, as the effect of only 1 drug at 1 dose was evaluated.…”

“…A number of RCTs have reported on the effects of daily PDE5i use on postoperative erectile function with discordant results. 5,6,14,15 In addition, there is strong evidence demonstrating that PDE5i affect and improve LUTS. 16 Moreover, an association between LUTS and erectile dysfunction has been clearly established, and recently reviewed by Mouli and McVary.…”

“…The study protocol has been previously published. 5 Postoperatively, patients were randomly administered the study drug for 1 year and were divided in 2 groups: (1) The "nightly" group (n = 50) received nightly 50 mg sildenafil dosing, and (2) the "on-demand" group (n = 50) received nightly placebo. Both groups were also given tablets for ondemand use, up to 6 per month.…”

“…3 Therefore in addition to affecting post-RP potency rates, the use of PDE5i may affect recovery of urinary continence and/or urinary quality of life after RP. 4 While several randomized controlled trials (RCT) suggest that nightly use of PDE5i is no more beneficial than on-demand use in terms of improving long-term erectile function after nerve-sparing RP, 5,6 many urologists nevertheless still prescribe chronic PDE5i immediately after RP. 7 The present study is a secondary outcomes analysis from a published randomized clinical trial that compared 2 different dosing regimens of postoperative sildenafil (50 mg nightly vs. 50 mg on-demand) for 1 year after nerve-sparing minimally invasive RP.…”

“…7 The present study is a secondary outcomes analysis from a published randomized clinical trial that compared 2 different dosing regimens of postoperative sildenafil (50 mg nightly vs. 50 mg on-demand) for 1 year after nerve-sparing minimally invasive RP. 5 In this report, we evaluated the effect of postoperative sildenafil dosing regimens on the temporal recovery of urinary continence and urinary quality of life after nerve-sparing minimally-invasive RP as assessed by urinary subscales of the EPIC questionnaire.…”