Randomized, double-blinded, placebo-controlled crossover trial of treating erectile dysfunction with sildenafil after radiotherapy and short-term androgen deprivation therapy: results of RTOG 0215

Abstract

Introduction: Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT.

Aim: The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT.

Methods: In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data.

Main outcome measures: The primary end point was improved erectile function, as measured by the IIEF.

Results: The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤ 120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase.

Conclusions: This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.

Figure 1

CONSORT diagram.

Figure 2

Responses to International Index of Erectile Function (IIEF) Question 1 after each treatment. IIEF Q1: How often were you able to get an erection during sexual activity? Numbers in parentheses represent frequency counts. Responders (+) have score of: 4—most times or 5—almost always/always. n (x, y) represents response status to placebo and sildenafil treatments, respectively.

Figure 3

Mean International Index of Erectile Function (IIEF) scores at baseline and after each treatment. Scores: 0—no activity; 1—almost never/never; 2—a few times; 3—sometimes; 4—most times; 5—almost always/always. *IIEF Q1 (primary end point): how often were you able to get an erection during sexual activity? IIEF Q3: When attempting intercourse, how often were you able to penetrate your partner? IIEF Q4: During intercourse, how often were you able to maintain your erection after penetration? IIEF-erectile function (EF) domain score (Q1–Q5, Q15).