The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors ( PDE5-Is ) on penile function after nerve-sparing radical prostatectomy ( NSRP ) remains unclear.
The primary objective of the REACTT ( Randomised Placebo-controlled Study ) trial was to compare the efficacy of Tadalafil 5 mg once daily and Tadalafil 20 mg on demand versus placebo taken over 9 months in improving unassisted erectile function ( EF ) following nerve-sparing radical prostatectomy, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain ( IIEF-EF ) score greater than or equal to 22 after 6-wk drug-free washout (DFW ).
Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 ( SEP-3 ), and penile length.
The randomised, double-blind, double-dummy, placebo-controlled trial has included men less than or equal to 68 yr of age with adenocarcinoma of the prostate ( Gleason less than or equal to 7 ) and normal preoperative erectile function who underwent nerve-sparing radical prostatectomy at 50 Centres from nine European countries and Canada.
The 1:1:1 randomisation to 9 months of treatment with Tadalafil 5 mg once daily, Tadalafil 20 mg on demand, or placebo, was followed by a 6-wk drug-free washout and 3-mo open-label Tadalafil once daily ( all patients ).
Four hundred twenty-three patients were randomised to Tadalafil once daily ( n=139 ), on demand ( n=143 ), and placebo ( n=141 ).
The mean age was 57.9 yr of age; 20.9%, 16.9%, and 19.1% of patients in the Tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores greater than or equal to 22 after drug-free washout ; odds ratios ( OR ) for Tadalafil once daily and on demand versus placebo were 1.1 ( p=0.675 ) and 0.9 ( p=0.704 ).
At the end of double-blind treatment ( EDT ), least squares ( LS ) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference ( MCID: ΔIIEF-EF greater than or equal to 4 ) in both Tadalafil groups; for SEP-3 ( MCID greater than or equal to 23% ), this was the case for Tadalafil once daily only.
Treatment effects versus placebo were significant for Tadalafil once daily only ( IIEF-EF: p=0.016; SEP-3: p=0.019 ).
In all groups, IIEF-EF and SEP-3 decreased during drug-free washout but continued to improve during open-label treatment.
At month 9 of double-blind treatment, penile length loss was significantly reduced versus placebo in the Tadalafil once daily group only ( LS mean difference 4.1mm; p=0.032 ).
In conclusion, Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following nerve-sparing radical prostatectomy, and data suggest a potential role for Tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes.
Unassisted erectile function was not improved after cessation of active therapy for 9 months. ( Xagena )
Montorsi F et al, Eur Urol 2014: Published online