Collaborative Review – Prostate CancerPhosphodiesterase Type 5 Inhibitors in Postprostatectomy Erectile Dysfunction: A Critical Analysis of the Basic Science Rationale and Clinical Application
Introduction
Radical prostatectomy (RP) is a commonly used treatment for localized prostate cancer in patients with a life expectancy of at least 10 yr [1]. The number of RPs has been increasing annually, and currently many patients are treated at younger ages [2]. Erectile dysfunction (ED) is the most common complication in these patients, having a significant negative impact on patients’ health-related quality of life and well-being [3]. Erectile function may take up to 4 yr to return, even in younger men with normal preoperative potency who have undergone bilateral nerve-sparing radical prostatectomy (BNSRP) [4], [5], [6]; however, 20–80% of these patients may never return to normal erectile function [7].
The advent of phosphodiesterase type 5 inhibitors (PDE5-Is) revolutionized ED treatment with an average success rate of 60–70% in the general ED population [8]. Nevertheless, these rates are significantly lower and vary considerably in post-RP ED patients [7]. New insights into the pathophysiology of post-RP ED have led to the development of penile rehabilitation strategies. These new strategies are promising, but they are still controversial due to the lack of strong evidence [9].
Section snippets
Evidence acquisition
This review aims to elucidate the current knowledge on the pathophysiologic mechanisms of post-RP ED, to assess the need for penile rehabilitation following surgery, and to analyze the basic science rationale of PDE5-I as well their clinical applications for the prevention and treatment of post-RP ED. A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008. An electronic search was conducted that
Pathophysiology of postprostatectomy erectile dysfunction
ED becomes clinically evident immediately after RP. This pattern is associated with nerve injury to the corpora cavernosa during surgery. Even in BNSRP, some trauma to the nerves, known as neuropraxia, is inevitable due to their anatomical proximity to the prostate. Commonly hypothesized causes of post-RP ED include nerve traction/percussion, thermal damage due to electrocautery use, nerve ischemia due to vascular injury, and local inflammatory effects associated with surgical trauma [10].
Conclusions
Data from limited clinical studies show that PDE5-Is are efficacious in the treatment of post-RP ED. While experimental evidence suggests that PDE5-Is can prevent smooth-muscle apoptosis and fibrosis related to ED after RP in the animal model, these findings have not yet been replicated in humans. Therefore, their use in penile rehabilitation programs remains controversial. More prospective, randomized, placebo-controlled studies are needed to firmly establish efficacy of PDE5-Is in
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