Efficacy of Phosphodiesterase Type 5 Inhibitors in Patients With Erectile Dysfunction After Nerve-Sparing Radical Prostatectomy

A Systematic Review and Meta-Analysis

Hyeok Jun Goh; Jeong Min Sung; Kwang Hyun Lee; Jung Ki Jo; Kyu Nam Kim


Transl Androl Urol. 2022;11(2):124-138. 

In This Article

Abstract and Introduction


Background: Nerve-sparing radical prostatectomy (NSRP) had to be performed because approximately 94% of patients are diagnosed with localized prostate cancer (PCa). Although NSRP is generally done to improve functional outcomes, erectile dysfunction (ED) is one of the most prevailing complications after radical prostatectomy (RP). Phosphodiesterase type 5 inhibitors (PDE5-Is) are the most well-known treatment agent for postoperative ED. This study aimed to assess the efficacy of PDE5-Is in patients with ED after NSRP.

Methods: In this systematic literature review, randomized controlled trials on the efficacy and safety of PDE5-Is in patients who underwent NSRP were searched in MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the OVID platform. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Review Methods. The quality of the evidence of the outcome data was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Results: A total of 14 trials involving 2,822 patients were included. Significant improvements in the International Index of Erectile Function—Erectile Function (IIEF) domain score [mean difference (MD) =4.93; 95% confidence interval (CI): 4.14–5.71; P<0.00001] and erectile function recovery events [odds ratio (OR) =2.06; 95% CI: 1.45–2.94; P<0.0001] were observed after PDE5-I treatment. A higher positive response to Sexual Encounter Profile (SEP) question 2 (OR =2.27; 95% CI: 1.80–2.86; P<0.00001) and question 3 (OR =2.78; 95% CI: 1.97–3.91; P<0.00001) was also found after PDE5-I treatment. However, the incidence of treatment-emergent adverse events (TEAEs) was higher after PDE5-I treatment than after placebo treatment (OR =2.91; 95% CI: 1.84–4.61). Furthermore, the incidence of headache (OR =3.38; 95% CI: 2.40–4.75) and flushing (OR =9.44; 95% CI: 4.30–20.70) was also significantly higher after PDE5-I treatment (P<0.00001). In terms of the quality of the evidence of the outcome data, inconsistency problems were detected in all outcomes and imprecision problems in most outcomes.

Discussion: PDE5-I treatment was more effective to placebo treatment in patients with ED after NSRP. No clinically serious complications were found in spite of the incidence of TEAEs being higher after PDE5-I treatment.


One in six men had been diagnosed with prostate cancer (PCa) in their lifetime, making PCa the most common type of cancer among men in Western countries.[1,2] Approximately 94% of patients are diagnosed with localized PCa and thus need to undergo nerve-sparing radical prostatectomy (NSRP).[2,3] The number of radical prostatectomy (RP) operation has been rapidly increasing over years, and the age of patients seeking for this treatment has also increased correspondingly.[4]

Despite the fact that NSRP is usually performed to promote the functional outcomes, such as erectile function, erectile dysfunction (ED) results frequently after the procedure. Postoperative ED has been reported in 15–18% of patients who undergo NSRP.[5,6] It is a condition that can potentially take a toll on the patients' everyday life.[4] Therefore, if postoperative ED is less likely to occur, more patients will decide to receive NSRP.[7] Various factors affect the development and severity of postoperative ED; these include patient age, preoperative potency, stage of the tumor, and surgeon's experience.[8–12] Postoperative ED can also cause vascular damage, neural injury, and smooth muscle damage.[13,14]

The emergence of phosphodiesterase type 5 inhibitors (PDE5-Is) has innovated ED treatment with a success rate of approximately 60–70%.[15,16] PDE5-Is are the most common treatment agent for postoperative ED. The efficacy and adverse effects of PDE5-Is have been reported; however, there is insufficient evidence to demonstrate the optimal use of PDE5-Is for penile rehabilitation. Several errors were found in meta-analyses and systematic reviews that have been performed to assess the efficacy and adverse effects of PDE5-Is.[17–19] Therefore, we performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDE5-Is in patients with ED after NSRP.

We present the following article in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-21-881/rc).