Efficacy of Tadalafil in Penile Rehabilitation Started Before Nerve-Sparing Robot-Assisted Radical Prostatectomy: A Double-Blind Pilot Study

Abstract

Background Despite the widespread practice of nerve-sparing robot-assisted radical prostatectomy (nsRARP) for the treatment of localized prostate cancer (PCa), erectile dysfunction remains a significant sequela of radical prostatectomy. Aim This study aimed to compare the efficacy of tadalafil 5 mg once daily for erectile function recovery in patients who underwent nsRARP according to the timing of rehabilitation initiation. Methods In this double-blind, prospective pilot study, a total of 41 patients who underwent nsRARP were randomly assigned into 2 groups according to the timing of rehabilitation initiation. In the preRARP group (n = 20), tadalafil was started 2 weeks before nsRARP, and in the postRARP group (n = 21), it was started 4 weeks after nsRARP. Erectile function recovery after nsRARP was defined as an International Index of Erectile Function (IIEF-5) score of ≥17. Outcomes The measures of EF recovery were the changes in IIEF-5 score. Results The rate of erectile function recovery at 12-month follow-up was 80.0% and 71.4% in the preRARP and postRARP groups, respectively. The mean differences between baseline and postoperative IIEF-5 scores at 1-, 3-, 6-, and 12-month follow-up were −11.7 ± 3.2, −7.4 ± 3.2, −5.6 ± 1.5, and −4.1 ± 1.1 in the preRARP group and −14.7 ± 4.7, −12.0 ± 5.0, −9.7 ± 3.9, and −6.0 ± 3.1 in the postRARP group, respectively (1-month, P = .259; 3-months, P = .077; 6-months, P = .014; 12-months, P = .007). Clinical implications Preoperative tadalafil 5 mg once a day could be used effectively and safely as a strategy for penile rehabilitation after nsRARP. Strengths and Limitations This study is the first prospective trial of penile rehabilitation with tadalafil 5 mg once a day prior to nsRARP. This is a pilot study with the limitations of a small sample; further and large-scale studies with multiple cohorts, such as an untreated control group and an early immediate rehabilitation group for EF recovery, are needed. Conclusion This study suggests that preoperative penile rehabilitation using tadalafil may lead to better erectile function recovery than postoperative penile rehabilitation using tadalafil.

Erectile Dysfunction in Pelvic Cancer Survivors and Current Management Options

“…At 12 months, the recovery of unassisted EF was achieved in 80% and 71% of patients, respectively, with no statistically significant difference observed. Moreover, the authors concluded that preoperative tadalafil 5 mg/day may offer benefits in penile rehabilitation [ 70 ]. A systematic review informed researchers that treatments started before surgery (PFMT, oral medications, and vacuum devices) may aid in EF recovery and that frequent information delivery between the patient and partner also impact on sexual recovery [ 11 , 70 ].…”

“…Moreover, the authors concluded that preoperative tadalafil 5 mg/day may offer benefits in penile rehabilitation [ 70 ]. A systematic review informed researchers that treatments started before surgery (PFMT, oral medications, and vacuum devices) may aid in EF recovery and that frequent information delivery between the patient and partner also impact on sexual recovery [ 11 , 70 ]. However the recommended time to start penile rehabilitation is 1–4 weeks after RP [ 71 ].…”

“…This induces an increase in cGMP that causes smooth muscle relaxation and consequently increased blood flow to the penis, resulting in and maintaining an erection [ 9 ]. However, nerve activation is required to initiate cGMP synthesis, which can explain why only 0 to 15% of the patients treated by non-NS RP respond to PDE5-I vs. 35 to 75% of those treated by NS RP [ 4 , 11 , 70 ].…”

“…PDE5-Is are considered to constitute the first-line treatment for postoperative NS RP ED due to their safety, efficacy profile and good tolerability without serious adverse events [ 70 , 72 , 73 , 74 ]. The use of DE5-I at any dosage and formulation is better than the use of placebo [ 70 , 72 , 73 , 75 ].…”

“…A recent systematic review included 2711 patients who were compared in categories of placebo, only pelvic floor muscle training and 100 mg sildenafil at regular doses (once daily or nightly). This showed that after NS RP, treatment with PFMT and early 100 mg sildenafil regular dose (i.e., once daily or nightly) are the best penile rehabilitation strategies with which to improve EF recovery rates at the end of the washout period and that the on-demand dose of PDE5-Is should not be recommended for use in penile rehabilitation [ 69 , 70 ].…”