Dataset Information

Effects of tadalafil once daily or on demand versus placebo on time to recovery of erectile function in patients after bilateral nerve-sparing radical prostatectomy.

ABSTRACT:

Purpose

We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP).

Methods

Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country).

Results

A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW.

Conclusions

Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo.

SUBMITTER: Moncada I

PROVIDER: S-EPMC4480825 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUnderstanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies.ObjectiveTo describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT).Design, setting, and participantsRandomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada.InterventionPostsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment.Outcome measurements and statistical analysisThree decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group.Results and limitationsThe first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor.ConclusionsExploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level.Patient summaryUnderstanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF.Trial registrationClinicalTrials.gov, NCT01026818.

Project description:Prostate cancer is relatively common cancer occurring in males. Radical prostatectomy (RP) is the most effective treatment for a localized tumor but erectile dysfunction (ED) is common complication, even when bilateral nerve-sparing RP (BNSRP) is performed. Clinical trials have shown varied effectiveness of phosphodiesterase type-5 inhibitors (PDE5-Is) for treatment of post-BNSRP ED, but there remains controversy over the application of this treatment and no formal systematic review and meta-analysis for the use of PDE5-Is for this condition has been conducted. This review was to systematically assess the efficacy and safety of oral PDE5-Is for post-BNSRP ED. A database search was conducted to identify randomized controlled trials (RCTs). The comparative efficacy of treatments was analyzed by fixed or random effect modeling. Erectile function was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) question-2, 3 and the Global Assessment Question (GAQ). The rate and incidence of adverse events (AEs) were determined. The quality of included studies was appraised using the Cochrane Collaboration bias appraisal tool. Eight RCTs were included in the analyses. PDE5-Is were effective for treating post-BNSRP ED compared to placebo when erectile function was determined using the IIEF score [mean difference (MD) 5.63, 95% confidence interval (CI) (4.26-6.99)], SEP-2 [relative risk (RR) 1.63, 95% CI (1.18-2.25) ], SEP-3 [RR 2.00, 95% CI (1.27-3.15) ] and GAQ [RR 3.35, 95% CI (2.68-4.67) ]. The subgroup analysis could find a trend that longer treatment duration, higher dosage, on-demand dosing, sildenafil and mild ED are associated with more responsiveness to PDE5-Is. PDE5-Is were overall well tolerated with headache being the most commonly reported AE. Our data provides compelling evidence for the use of PDE5-Is as a primary treatment for post-BNSRP ED. However, further studies are required to optomize usage parameters (such as dosage and duration of treatment).

Project description:BackgroundThis multicenter, randomized, double-blind, double-dummy, placebo-controlled trial primarily evaluated the efficacy of tadalafil once-daily (OaD) or on-demand ("pro-re-nata"; PRN) treatment, started early post-nsRP. Secondary outcome-measures on quality-of-life (QoL) and treatment satisfaction are reported.MethodsPatients, aged <68 yrs, with adenocarcinoma of the prostate (Gleason ≤ 7, normal preoperative erectile function [EF]) were randomized post-nsRP 1:1:1 to 9-month treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout and 3-month open-label tadalafil OaD treatment (OLT). The main outcome measures were Changes in Expanded Prostate Cancer Index Composite (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Self-Esteem and Relationship (SEAR) questionnaires (mixed-model-for-repeated-measures, including terms for treatment, visit, treatment-by-visit interaction, age-group, country, baseline-score). LS means with 95% confidence interval (CI) are reported.Results423 patients were randomized to 3 treatment-groups: tadalafil OaD (N = 139), PRN (N = 143), or placebo (N = 141). In each group, 57 (41.0%), 58 (40.6%), and 50 (35.5%) patients were aged 61-68 yrs. At the end of double-blind treatment (DBT), patients' EPIC sexual domain-scores improved significantly with tadalafil OaD versus placebo (treatment effect [95% CI]: 9.6 [3.1,16.0]; p = 0.004); comparisons of PRN versus placebo at end of DBT, and comparisons of tadalafil OaD and PRN versus placebo after OLT were not significant. Only in older patients (61-68 yrs; age-by-treatment p ≤ 0.1), EPIC urinary incontinence domain-scores also improved significantly with tadalafil OaD versus placebo (overall treatment effect across all visits, 8.3 [0.4,16.1]; p = 0.040). Treatment satisfaction increased significantly in both tadalafil groups, EDITS total-scores increased significantly with OaD and PRN versus placebo during DBT (p = 0.005 and p = 0.041, respectively). At the end of OLT, improvement was significant for tadalafil OaD versus placebo only (p = 0.035). No significant differences were observed for SEAR.ConclusionsThese results suggest that chronic dosing of tadalafil improves QoL of patients post-nsRP. The improvement of urinary incontinence in elderly patients randomized to tadalafil OaD may contribute to this effect.Trial registrationwww.clinicaltrials.gov , NCT01026818.

Project description:BackgroundIntrafascial nerve-sparing prostatectomy has been currently applied based on the updated anatomic understanding of periprostatic cavernous nerves, in order to provide patients better postoperative recovery of continence and potency. The aim of our study is to perform a pooled analysis of available literatures regarding the functional outcomes following intrafascial nerve-sparing technique.MethodsThe authors performed database searches of articles published till October 2017 on PubMed using following keywords across the "title" and "abstract" field of the records: intrafascial, veil, curtain dissection, high anterior release, incremental nerve sparing, and radical prostatectomy. Fulfilled papers were screened and data were extracted independently by 3 reviewers. Main outcome was the postoperative continence and potency rate stratified by follow-up durations. Both 1-arm and comparative meta-analyses were performed and meta-regression models were conducted to evaluate the confounding factors.ResultsUsing the electronic search strategy, a total of 71 records were retrieved and 20 studies were finally included, of which 6 were surgical series and 14 were controlled studies. Our 1-arm meta-analysis summarized the pooled continence rates after intrafascial prostatectomy were 59.4%, 76.2%, 89.9%, and 92.2% at postoperative follow-up of 1, 3, 6, and 12 months, respectively. Regardless of the variance in potency definition, the pooled potency rates after intrafascial prostatectomy were 42.2%, 54.2%, and 72.2% at 3, 6, and 12 months, respectively. Comparative analysis showed that the intrafascial group offered better continence rates at 1, 3, and 6 months with an odds ratio (OR) of 2.38 (95% confidence interval [CI]: 1.73-3.26), 1.82 (95% CI: 1.18-2.82), and 2.19 (95% CI: 1.43-3.34) as compared with the interfascial group. Moreover, potency rate in the intrafascial group was higher at 12 months than in the interfascial group, with an OR of 2.44 (95% CI: 1.35-4.42).ConclusionBased on the limited evidence, our study demonstrated that intrafascial nerve-sparing prostatectomy could provide patients with earlier recovery of continence and better erectile function compared with conventional interfascial approach, but physiological mechanisms about this technique still need further study.