Vardenafil can Improve Continence Recovery after Bilateral Nerve Sparing Prostatectomy: Results of a Randomized, Double Blind, Placebo-Controlled Pilot Study

Abstract

Introduction Phosphodiesterase type 5 inhibitors (PDE5-I) have acquired an established role in the treatment of post-prostatectomy erectile dysfunction (ED). Several trials in men with ED and lower urinary tract symptoms associated with benign prostatic hyperplasia suggest that PDE5-I could improve both erectile function and urinary symptoms. Aim To assess the role of vardenafil in continence recovery after bilateral nerve sparing radical prostatectomy (BNS-RP). Methods Thirty-nine patients with prostate cancer were recruited. After BNS-RP, patients were double-blinded assigned to three arms: a) vardenafil on demand; b) vardenafil nightly; and c) placebo. Main Outcomes Measures Urinary function (UF) and urinary bother (UB) of University of California–Los Angeles Prostate Cancer Index questionnaire were assessed preoperatively and at 1, 3, 6, 9, 10, and 12 months. Twelve-month outcomes were compared to 1 month with a t-test. The differences in UF and UB (at 3, 6, 9, 10, and 12 months) between the three treatment arms were calculated by an analysis of variance. With ALLFIT we estimated half-maximal recovery times (ER50) and maximal recovery (Rmax) in three groups. Results The improvement of UF and UB between 1 and 12 months was significant in all arms except for placebo (UF: P = 0.125; UB: P = 0.089). Nightly resulted in greater UF at 3, 6, and 9 months and greater UB at 6 months compared with placebo (P = 0.042, P = 0.044 and P = 0.039); after nightly administration, patients presented higher UB than after on-demand use, 3 and 6 months postoperatively (P = 0.036 and P = 0.017). ALLFIT demonstrated a similar ER50 in all groups (2.6 months for both UF and UB) and indicated that nightly administration induced significant improvements in Rmax compared with placebo (both <0.0001). Conclusions Vardenafil can improve continence recovery after BNS-RP compared with placebo. The daily use of vardenafil seems to provide better continence rate, although it does not seem to influence the timing needed to achieve full continence.

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

“…2) and in the vardenafil trial by Gacci and colleagues. 4 It certainly is possible that there are differences between the effects of sildenafil and vardenafil on urinary convalescence after RP, but the similar data that resulted from our study, the Gacci study and previous reports using short-acting PDE5i post-RP all suggest that these drugs act very similarly in this setting. 18 Pertinently, Bittencourt and colleagues recently demonstrated that sildenafil relaxes human bladder tissue depending on the nitric oxide/cGMP pathway.…”

“…The authors reported improvements in urinary function and bother in patients taking nightly vardenafil compared to those taking it ondemand or taking placebo during the months after RP. 4 However, this improvement was entirely dependent on a significantly greater initial decline in urinary function and bother in the nightly vardenafil group, and a subsequent improvement from that state of decreased urinary function over time. Indeed by 12 months, urinary outcomes were equivalent in all groups, so another interpretation of their data is that nightly vardenafil delays urinary recovery until the first postoperative year.…”

“…17 Gacci and colleagues reported a small three-armed study that was similar to ours, using daily vardenafil, on-demand vardenafil, and a placebo group. 4 Based on this trial with only 12 to 14 patients per arm, the authors suggested that daily vardenafil use improved postoperative continence as determined by the UCLA-PCI (University of CaliforniaLos Angeles Prostate Cancer Index). The authors reported improvements in urinary function and bother in patients taking nightly vardenafil compared to those taking it ondemand or taking placebo during the months after RP.…”

“…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.…”

Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer

“…28 We also showed that the continence recovery after nerve-sparing prostatectomy for PCa was strictly correlated with recovery of SF: thus, we concluded that PDE5 inhibitors can exhibit an activity in the lower urinary tract, even in the absence of the prostatic gland, by a pathway not including prostate. 29 Therefore, the androgen-dependent PDE5 activity of the bladder wall can explain the significant correlation between erectile function and urinary symptoms exclusively in patients with adequate T. In our experience, this activity can be provided both by the relaxation of the smooth muscle and by the improvement in perfusion of the bladder wall. 30 …”