Changing Definitions of Erectile Recovery Has “No Major Impact” in REACCT Trial

Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy – Results from a Randomized Controlled Trial (REACTT)

John P. Mulhall, MD; Gerald Brock, MD; Matthias Oelke, MD; Mikkel Fode, MD, PhD; Kai A. Probst, MD; Carsten Henneges, PhD; Gianluca d'Anzeo, MD; Andrea Rossi; Hartwig Büttner, MD

ONLINE: June 2016 – The Journal of Sexual Medicine

DOI: http://dx.doi.org/10.1016/j.jsxm.2016.01.022


Introduction and Aims

After bilateral nerve-sparing radical prostatectomy, most men struggle with erectile dysfunction (ED). Ideally, patients would eventually regain the “normal” function they had before surgery, but recovery rates are estimated to range between 25% and 75%, depending on factors like a patient’s age, erectile function before surgery, and concurring medical conditions.

The International Index of Erectile Function (IIEF) Erectile Function domain (IIEF-EF) is commonly used to assess erectile function, with scores of 26 or above indicating “normal” function and scores of 22 to 25 indicating mild ED. However, past studies have used different definitions of “normal,” which makes evaluation difficult.

The original REACCT trial used an IIEF-EF score of 22 or higher as a benchmark for normal erectile function after postsurgical daily use of the phosphodiesterase type-5 inhibitor tadalafil.

The current study explores a different definition used for recovery of erectile function. The authors wanted to see whether patients’ function returned to its pre-surgery levels (IIEF-EF scores either in the 22-25 range or 26 or higher).

The Trial

The study involved 422 adult men younger than 68 years old who underwent bilateral nerve-sparing prostatectomy for localized prostate cancer in one of 9 European countries or Canada. Each man underwent pre-surgery and post-surgery screening visits. Within 6 weeks of surgery, the men were randomly assigned to one of three groups for the next 9 months:

Daily Group (139 men): Double-blind treatment with 5 mg of tadalafil once a day.

On Demand Group (142 men): Treatment with 20 mg of tadalafil taken on demand (e.g., when an erection was desired).

Placebo Group (141 men): No treatment.

This 9-month period was followed by a 6-week drug-free washout period. After that, all of the men had 3 months of open-label treatment with 5 mg of tadalafil taken once a day.

Results

Before surgery (baseline), 92.4% of the men had IIEF-EF scores of 26 or higher, and 7.4% had scores of 22-25.

Back-to-baseline achievements after 9 months of treatment were as follows:

  % Returning back to baseline
erectile function after
9 months of treatment
Daily  Group 22.3%*
On Demand  Group 11.3%*
Placebo Group 7.8%

*Significantly different from placebo

However, these results were not maintained after the drug-free washout period:

  After drug-free washout
Daily  Group 12.2%
On Demand Group 9.2%
Placebo Group 11.4%

Not significantly different

After the open-label treatment period (5 mg of tadalafil once a day), however, the back-to-baseline results had almost doubled for all 3 groups.

In comparing outcomes from the original REACCT definition (IIEF-EF score of 22 or higher) and the stricter definition (back to baseline), results demonstrated similar outcomes:

  Original definition
from previous
REACCT study
(IIEF-EF score of
22 or higher)
“Stricter” definition:
back to baseline
Daily Group 25.2% 22.3%
On Demand Group 19.7% 11.3%
Placebo Group 14.2% 7.8%

Not significantly different compared to original definition

Study Limitations

The authors noted these limitations:

• The 9-month treatment period was relatively short. An 18- to 24-month period would be ideal. Still, even in 9 months, some men saw improvements in their erectile function.

• The anxiety that accompanies a cancer diagnosis, as well as biopsy-related side effects, could have affected the men’s responses to the IIEF-EF questionnaire. However, most men had high IIEF-EF scores before surgery anyway.

Conclusions

Overall, the researchers concluded that changing the definition for erectile function recovery from an IIEF-EF score of 22 or higher to back-to-baseline function had “no major impact.”

Finally, the authors explained that taking 5 mg of tadalafil once a day improved drug-assisted erectile function when started soon after surgery, but had no effects on erectile function once the drug was stopped after 9 months.