What randomized trials compare daily versus on‑demand PDE5i for penile rehabilitation after radical prostatectomy?
Executive summary
Randomized trials directly comparing daily (scheduled/nightly) versus on‑demand phosphodiesterase type‑5 inhibitors (PDE5i) for penile rehabilitation after nerve‑sparing radical prostatectomy exist, but the largest and most rigorous studies generally did not find a clear superiority of daily dosing for return of unassisted erectile function; some signals favor specific secondary outcomes (for example, tadalafil once‑daily preserving penile length) and results are muddied by heterogeneous designs and methodological limitations (dropouts, timing, choice of drug) [1] [2] [3] [4].
1. Trials that randomized nightly/daily versus on‑demand — the headliners
A single‑institution, double‑blind randomized trial by Pavlovich et al. directly compared nightly versus on‑demand 50 mg sildenafil after minimally invasive nerve‑sparing radical prostatectomy and reported no difference in erectile recovery at one year, a result published in BJU International (nightly vs on‑demand sildenafil) [5] [1]. The multicenter trial led by Montorsi et al., the largest trial to examine nightly vardenafil versus on‑demand vardenafil and placebo in the postoperative setting, randomized 628 patients and likewise failed to show a clear benefit of nightly dosing for recovery of spontaneous erectile function, with on‑demand dosing performing at least as well in many analyses [6] [7].
2. Trials with mixed or different comparator designs that still inform the question
REACTT (tadalafil once‑daily vs on‑demand vs placebo) was a randomized controlled trial designed to evaluate once‑daily tadalafil compared with on‑demand tadalafil and placebo after bilateral nerve‑sparing radical prostatectomy and is frequently cited in guideline reviews; it showed benefits for some secondary endpoints such as penile length and morning erections but did not deliver an unequivocal advantage in return to baseline erectile function across the board [4] [2]. Smaller trials — for example studies that randomized nightly sildenafil versus placebo or trials examining three‑times‑per‑week tadalafil versus on‑demand regimens — add data but are underpowered or single‑center, limiting generalizability [6] [8].
3. What systematic reviews and meta‑analyses conclude
Systematic reviews and network meta‑analyses pooling RCTs report uncertainty about whether daily versus on‑demand PDE5i improves the rate of drug‑assisted or drug‑unassisted erectile function recovery after nerve‑sparing prostatectomy; pooled data across trials (thousands of men in some analyses) have not produced consistent evidence that scheduled daily therapy yields superior unassisted erectile recovery compared with on‑demand use, and the authors emphasize low to very‑low quality evidence in many comparisons [3] [9] [2].
4. Why trials disagree — methodological and biological caveats
Heterogeneity in agents (sildenafil, vardenafil, tadalafil, avanafil), dosing regimens (nightly, once daily, three‑times‑weekly), timing of therapy initiation after surgery, follow‑up duration, reliance on patient‑reported IIEF outcomes, variable dropout rates, and differing endpoints (drug‑assisted intercourse vs return to baseline spontaneous erections vs penile length) all complicate interpretation and likely explain inconsistent trial findings; reviewers explicitly call for better‑designed RCTs addressing timing, dose, and duration to resolve remaining questions [3] [6] [7].
5. Practical takeaway grounded in the evidence
Randomized evidence directly comparing daily versus on‑demand PDE5i exists and tends not to support a large, consistent advantage of nightly/scheduled dosing for recovery of unassisted erectile function after nerve‑sparing radical prostatectomy, although certain trials (notably REACTT) reported benefits for secondary outcomes such as penile length with daily tadalafil; clinicians and patients must weigh these nuanced trial results, differences between drugs (half‑life matters), and individual priorities when choosing a rehabilitation strategy, recognizing that reviewers call the overall quality of evidence limited and further RCTs are needed [1] [4] [3] [2].