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Authors Pisansky TM, Pugh SL, Greenberg RE, Pervez N, et al.
Review Date April 2014
Citation JAMA 2014;311(13):1300-1307
Erectile dysfunction (ED) is common in men following radiotherapy treatment for prostate cancer. Regular administration of a phosphodiesterase-5 (PDE5) inhibitor has been shown to reduce endothelial dysfunction and improve cavernosal vasodilatation and erectile function in a general population of men with ED compared with on-demand dosing. Howeever, other placebo-controlled studies using sildenafil or vardenafil for ED prevention in men with prostate cancer undergoing radiotherapy or surgery have had mixed results. Tadalafil performs well compared with other PDE5 inhibitors and has pharmacokinetic properties that make it suited to once-daily dosing. Prevention of ED due to prostate cancer treatment could help to improve patient satisfaction with treatment and psychosocial functioning.
The primary aim was to determine whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer. The secondary aims were to assess whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected.
The design was a stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomisation. The study included 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up until March 2013.
242 men were randomised, 121 to each arm of the trial: one arm was assigned to receive 5 mg of tadalafil daily and the other arm a placebo, each for 24 weeks from the start of external radiotherapy (63%) or brachytherapy (37%). Participant-reported response to the International Index of Erectile Function (IIEF) was recorded before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners were also asked to respond to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year.
The primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary outcomes were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year; patient-related predictors of tadalafil response; and adverse events.
Among 221 participants with data that could be included in the analysis, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (p = 0.49); an absolute difference of 5% (95% CI, −9% to 19%). There was also no statistically significant difference at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; p = 0.93).
Tadalafil was not associated with significantly improved overall sexual function or satisfaction as shown by no statistically significant difference between groups in any domain subscale. The partners of 42 men assigned tadalafil and 40 assigned placebo completed the Sexual Adjustment Questionnaire for Partners. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners.
This study did not show a statistically significant effect of daily use of tadalafil on erectile function, compared with placebo, among men undergoing radiotherapy for prostate cancer. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. However, study limitations such as sample size issues, may have reduced the likelihood of showing an effect.
Points to Note
- The authors state this is the first study to evaluate tadalafil for prevention of ED in men treated with radiotherapy for prostate cancer.
- The primary outcome measure was the response to a single question on the IIEF. This measure has been used in other studies and was thought to be the most appropriate for this study given it is a measure of erectile function that is independent of sexual intercourse (a consideration in a study of older men).
- There was an absolute difference of 5% between groups in the primary outcome but this was not statistically significant, leading the authors to state there was “no support” for PDE5 inhibitor use to prevent ED associated with radiotherapy (either highly conformal external radiotherapy or low dose rate brachytherapy).
- There was significant attrition over the course of the study (in addition to the original sample size calculation having been based on identifying a 20% difference between groups), higher in the placebo than the treatment group, perhaps precluding identifying a smaller effect.
- It is possible that other dosing schedules or other PDE5 inhibitors may have given different results.