Figure 20.1
Biochemical alteration after neuro-vascular damage during radical prostatectomy. PGE-1 prostaglandin E1, TGF-B1 transforming growth factor b1, ET-1 endothelin-1, nNOS neuronal nitric oxide synthase, ED erectile dysfunction
Penile Rehabilitation for Erectile Dysfunction
Penile rehabilitation (PR) is defined as use of any drug or device for preservation of erectile function after radical pelvic surgery (e.g. RP or cystectomy). An accumulation of evidence indicates that penile rehabilitation program should be recommended for all patients who will undergo RP [5]. According to a well-designed study with a great number of patients, after nerve sparing surgery performed by high volume surgeons, erectile function recovery rates at 3. Year follow up were 73 and 37 % for PDE5Is user and non-user group respectively [6]. The aim of penile rehabilitation is preserve erectile function and minimize ED after surgery. Numerous studies show that penile rehabilitation is absolutely superior over controls for patients who undergo nerve sparing surgery in terms of erectile function preservation [7]. A review of the literature demonstrates a lack of evidence based data to determine the optimal treatment modality for EF recovery after RP. However recently a large number of studies focused on designated PR program have been published. According to current literature, phosphodiesterase type 5 inhibitors (PDE5Is) are the first line treatment while intra-cavernozal injection (ICI), vacuum erection device(VED) and intraurethral alprostadil (IUA) are optional second line treatments. Penile prosthesis is accepted as the final treatment modality [8].
Strategy and timing of PR are still not clear but starting PR as early as possible (removal of the urethral catheter or within 1 month after surgery) and even prior to penile structure injury is vital and may improve long time erectile function. Furthermore few studies even suggest “massive treatment”, PR initiated 1–2 weeks prior to surgery decrease ED rate [9, 10].
The role of PDE5Is at post RP ED treatment has been investigated via both animal and human studies. The cause-effect relation between RP, nerve-vascular damage, and hypoxia, apoptosis, venous leak and fibrosis of cavernous tissue has been shown in the animal studies. The early usage of PDE5Is may prevent this process and preserve erectile function [11].
Nowadays, sildenafil, tadalafil and vardenafil are the most the commonly used PDE 5Is for ED after RP. Numerous penile rehabilitation programs using different PDE5Is are being conducted in current clinical practice (Table 20.1) [12, 13]. According to recent literature there is no consensus on the ideal PDEIs agent, dosage or timing for penile rehabilitation. While both on demand and chronic usage of PDE5Is are beneficial for patients with post RP ED when compared to control group, there is no evidence based data comparing the success rates between these two treatment regimens [14–16]. However a few studies derived from randomized placebo controlled trial (REACT data) showed that daily tadalafil 5 mg usage was superior to placebo and on demand treatment in terms of number of morning erections, EF recovery rate, quality of life improvement and penile length loss reduction were [17–19].
Table 20.1
Clinical studies with PDE5 inhibitors in penile rehabilitation after radical prostatectomy
Authors | Inclusion criteria/number of patients(pts) | Design of study | Treatment period | Treatment | Outcomes |
|---|---|---|---|---|---|
Kim et al. (2016) [15] | IIEF>22 No ED before surgery NSRP N:74 pts with ED | Prospective, randomized, double-blind, placebo-con-trolled, single institution | Starting midnight surgery At the end of double blind treatment (12 month) washout (13 month) | Nightly Sildenafil 50 mg+ on-demand sildenafil 100 mg vs On-demand sildenafil 100 mg and nightly placebo (1:1) | No significant differences were seen in return to normal EF between treatment group vs. placebo based on RigiScan TM and IIEF score at any time point. Return to normal EF based RigiScan: 40 % vs 40 % as measured by the IIEF-EF: 29.0 % vs. 32.4 % for treatment vs. placebo arms |
Montorsi et al. (2014) [10] | IIEF>22 Age<68 No ED PCA:cT1c-T2c NSRP N:423 pts with ED | Randomized, double-blind, double-dummy, multicenter placebo-controlled trial | At the end of double blind treatment (9 month) Washout (10.5 month) Open label (13.5 month) | Tadalafil 5 mg daily, tadalafil 20 mg on demand vs. placebo (1:1:1) | Treatment effects versus placebo were significant for tadalafil once daily only. At month 9, penile length loss was significantly reduced versus placebo in the tadalafil once daily group only |
Mulhall et al. (2013) [13] | Age: 18–70 Pts with ED least 6 months after RP NSRP N:298 pts with ED | A randomized double-blind, placebo controlled, parallel group phase 3 study | 3 months | 100 or 200 mg avanafil vs placebo | After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo |
Montorsi et al. (2008) | No ED history IIEF>25 Age: 18–64 NSRP N:628, pts with ED | A randomized, double-blind, double-dummy, multicenter, parallel group study | At the end of double blind treatment (9 month) Washout (11 month) Open label (13 month) | Vardenafil 10 mg daily, Vardenafil 10 or 20 mg on demand vs. placebo | On-demand vardenafil treatment resulted in significantly greater IIEF-EF scores and better SEP-3 response rates than placebo over the entire treatment period |
Montorsi et al. (2004)
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