What randomized trials compare vacuum erection devices, PDE5 inhibitors, and intracavernosal injections for penile rehabilitation after radical prostatectomy?
Executive summary
Randomized trials exist for each modality—PDE5 inhibitors (PDE5i), vacuum erection devices (VED), and intracavernosal injections (ICI)—and several randomized studies and systematic reviews report benefits from each or from combination strategies, but there is no large, definitive randomized trial that directly pits all three modalities (VED vs PDE5i vs ICI) in a single head‑to‑head comparison with long‑term follow‑up [1] [2] [3].
1. What randomized evidence exists for PDE5 inhibitors after radical prostatectomy
Randomized, placebo‑controlled trials have tested nightly or scheduled PDE5 inhibitors after nerve‑sparing radical prostatectomy and shown improvements in erectile function metrics during treatment, with influential trials such as Padma‑Nathan’s sildenafil trial and subsequent multicenter studies reporting superior erectile function scores for PDE5i compared with placebo during the treatment period [4] [2] [5]. Meta‑analytic pooling of randomized trials also found that PDE5i use is associated with greater on‑treatment erectile function scores compared with placebo, although some analyses emphasize that evidence that PDE5i improve long‑term spontaneous erectile recovery after washout is limited or inconsistent [1] [2] [5].
2. Randomized trials and RCT evidence for vacuum erection devices
Randomized trials of early VED use after prostatectomy have been conducted, including trials that randomized men to daily short sessions of VED versus no device and trials comparing VED monotherapy to PDE5i monotherapy in shorter randomized cohorts, showing improvements in IIEF scores and preservation of penile length in many studies [6] [7] [3]. Systematic reviews and meta‑analyses identify multiple randomized and prospective trials of VED—often heterogeneous in schedule and duration—and conclude that VED use improves erectile function scores and penile length compared with controls, but emphasize the need for larger, multicenter randomized trials with longer follow‑up [3] [8] [9].
3. Randomized evidence for intracavernosal injections and comparisons with other modalities
Early randomized trials evaluated intracavernosal injections (ICI), most notably prospective randomized work on alprostadil injections showing effects on recovery of spontaneous erections when used early after surgery; these injection studies are among the earliest RCTs in the penile rehabilitation literature [8] [10]. More recent randomized or prospective programs have examined ICI as part of combination rehabilitation strategies and reported functional gains during treatment, while contemporary safety analyses report acceptable priapism risk when ICI is combined with PDE5i [11]. However, direct randomized head‑to‑head trials that compare ICI versus VED versus PDE5i as separate arms are scarce.
4. Trials that compared combinations or two modalities head‑to‑head
Several randomized and controlled studies have examined combinations (VED + PDE5i) or compared one modality with another—examples include RCTs or prospective randomized controlled designs comparing scheduled PDE5i, scheduled VED, and combined therapy, which suggest additive or synergistic benefits for combination regimens in some endpoints [12] [7] [13]. Systematic reviews note that among the literature there are randomized controlled trials that evaluated VED alone, PDE5i alone, and combination regimens, and that seven randomized controlled trials were identified in some reviews, but heterogeneity in protocols, timing, and endpoints limits direct aggregation [3] [10].
5. Bottom line on direct randomized comparisons and gaps in the evidence
Randomized data support that PDE5i, VED, and ICI each can improve erectile function during the treatment period and help preserve penile length, and meta‑analysis of randomized trials shows an overall benefit of rehabilitation interventions versus controls [1] [5]. Yet there is not a single large, definitive randomized trial that cleanly randomizes patients into three parallel arms (VED vs PDE5i vs ICI) with standardized timing and long‑term washout assessment; most trials are two‑arm comparisons, short to intermediate in duration, or combine therapies, leaving important comparative effectiveness questions open [3] [2] [10]. Clinical practice therefore favors PDE5i as first‑line with VED and ICI as adjuncts or second‑line—an approach reflected in practice surveys—while calls for larger multicenter RCTs remain prominent in the literature [14] [2].