Gerald Brock, MD
Daily treatment with the PDE-5 inhibitor tadalafil (Cialis) led to a significant decrease in loss of penile length among men who had undergone bilateral nerve-sparing radical prostatectomy, a randomized trial showed.
Patients treated daily with tadalafil had 4.1 mm less reduction in stretched penile length (SPL) at the end of 9 months, as compared with placebo-treated men. However, use of a higher dose of the drug on an as-needed basis did not improve penile length compared with placebo. Additionally, morning penile tumescence and ability to achieve erections suitable for intercourse also improved significantly with daily tadalafil versus placebo, according to a presentation at the American Urological Association meeting in Orlando.
“These data suggest that tadalafil at a dose of 5 mg daily, if started early after surgery, protects against penile length loss and may help prevent structural cavernosa changes after nerve-sparing radical prostatectomy,” said Gerald Brock, MD, professor of urologic surgery at the University of Western Ontario in London.
Sexual dysfunction occurs frequently after nerve sparing radical prostatectomy. In general, a majority of men who had normal erectile function before surgery recover function over the span of several years, said Brock.
Penile shortening, a common consequence of radical prostatectomy, is associated with sexual dysfunction and adversely affects quality of life. Studies involving penile tissue obtained from men before and after radical prostatectomy showed that elasticity declined progressively after surgery and formation of collagenous fibrous tissue increased.
In a preclinical model of diabetes-associated sexual dysfunction, chronic low-dose tadalafil led to an increase in penile smooth muscle and elastic tissue, a decrease in fibrous tissue, and improvement in erectile function, said Brock.
To evaluate the effects of tadalafil in the post-prostatectomy setting, investigators performed a randomized, controlled clinical trial, allocating patients to 5-mg tadalafil once a day (n = 139), 20-mg tadalafil as needed (n = 143), or placebo (n = 141). Randomized treatment continued for 9 months, followed by a 6-week washout period and an additional 3 months of open-label treatment with tadalafil at 5 mg once daily.
The primary endpoint was improvement in unassisted erectile function at the end of the 6-week washout period. Investigators defined the outcome as a score ≥22 on the erectile function component of the International Index of Erectile Function (IIEF-EF). Secondary endpoints were absolute values and changes from baseline in IIEF-EF score, positive responses to the Sexual Encounter Profile (SEP), and change in SPL in the flaccid state.
The trial involved 423 men, all of who had normal erectile function prior to nerve-sparing radical prostatectomy for localized prostate cancer (Gleason score ≤7, PSA ≤10 ng/mL).
Analysis of the primary endpoint showed that significantly more patients randomized to daily tadalafil had an IIEF-EF score ≥22 at 9 months compared with placebo (25.2% vs 14.2%; P
= .016). Use of tadalafil on demand did not lead to significant improvement versus the placebo group (18.7% vs 14.2%).
After the 6-week washout, the proportion of patients with IIEF-EF score ≥22 was 20.9% with daily tadalafil, 16.9% with tadalafil on demand, and 19.1% with placebo. Neither tadalafil group differed significantly from the placebo group.
Upon completion of the 3-month period of open-label tadalafil treatment, 55.3% of patients initially randomized to daily tadalafil had IIEF-EF values ≥22 versus 37.8% of the placebo group (P
= .010). Additionally, 47.9% of patients originally randomized to tadalafil on demand met the primary endpoint, but the difference from placebo did not achieve statistical significance.
Comparison of SPL before surgery and at the end of randomized treatment showed an average loss of SPL of 2.2 mm among patients who received daily tadalafil compared with 6.3 mm in the placebo group (P
= .032). Patients randomized to on-demand tadalafil had a mean loss in SPL of 7.9 mm, which was significantly different from daily tadalafil (P
Loss of SPL did not differ significantly between patients who had a perfect Nelson nerve-sparing score (2) or a nonperfect score (>2). The type of surgery (laparoscopic, robotic, or open prostatectomy) did not influence SPL.
Significantly more patients in both of the tadalafil groups answered affirmatively regarding the ability to achieve at least some degree of erection compared with placebo at 9 and 13.5 months. Additionally, significantly more patients randomized to daily tadalafil reported morning penile tumescence as the initial sign of recovery of erectile function at 9 and 13.5 months and improvement in the ability to engage in sexual intercourse at 9 months.