Elsevier

European Urology

Volume 55, Issue 2, February 2009, Pages 334-347
European Urology

Collaborative Review – Prostate Cancer
Phosphodiesterase Type 5 Inhibitors in Postprostatectomy Erectile Dysfunction: A Critical Analysis of the Basic Science Rationale and Clinical Application

https://doi.org/10.1016/j.eururo.2008.10.028Get rights and content

Abstract

Context

Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs.

Objective

To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED.

Evidence acquisition

A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed.

Evidence synthesis

Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine.

Conclusions

PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.

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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