Effect of tadalafil on erectile function in patients after robotic-assisted radical prostatectomy with unilateral or bilateral nerve sparing

I-Yen Lee; Min-Che Tung; Chao-Yu Hsu; Jue-Hawn Yin; Yu-Kang Chang; Wei-Chun Weng; Li-Hua Huang; Zhon-Min Huang; Cheng-Kuang Yang; Yen-Chuan Ou

doi:10.4103/UROS.UROS_74_18

ORIGINAL ARTICLE

Year : 2019 | Volume : 30 | Issue : 1 | Page : 14-18

Effect of tadalafil on erectile function in patients after robotic-assisted radical prostatectomy with unilateral or bilateral nerve sparing

I-Yen Lee¹, Min-Che Tung¹, Chao-Yu Hsu¹, Jue-Hawn Yin¹, Yu-Kang Chang², Wei-Chun Weng¹, Li-Hua Huang¹, Zhon-Min Huang¹, Cheng-Kuang Yang³, Yen-Chuan Ou⁴
¹ Divisions of Urology, Department of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan
² Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan
³ Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
⁴ Division of Urology, Department of Surgery; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

Date of Web Publication

2-Jan-2019

Correspondence Address:
Yen-Chuan Ou
No.1650 Taiwan Boulevard Section 4, Taichung Veterans General Hospital, Taichung 40705
Taiwan

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/UROS.UROS_74_18

Abstract

Objective: Erectile dysfunction (ED) is a major complication of radical prostatectomy. Despite advances in surgical techniques, the postoperative continence and potency rates are still not satisfactory. Many studies have reported experiences with penile rehabilitation using tadalafil for patients receiving nerve-sparing robotic-assisted radical prostatectomy, but similar reports are still lacking in Taiwan. Patients and Methods: We collected 163 patients that had undergone unilateral or bilateral nerve-sparing robotic-assisted radical prostatectomy from January 2013 to December 2014 in Tungs' Hospital. One month after operation, 5 mg tadalafil once daily was prescribed for 54 patients whose Foley's catheter had been removed and who had ED. We recorded the International Index of Erectile Function (IIEF-5) score at the 12^th month after surgery. We defined postsurgery IIEF-5 ≥22 as potency or no ED. We compared the differences in clinical parameters and postsurgery potency rates between patients with or without tadalafil treatment. Results: The postsurgery potency rates of those with tadalafil treatment were significantly higher than that of those without tadalafil treatment (55.6% vs. 32.1%) after a 1-year follow-up observation. The mean (standard deviation) of IIEF-5_preamong those with and without tadalafil treatment was 21.3 (4.5) and 19.2 (4.2), respectively. There were no significant differences in baseline clinical condition parameters between patients with potency with or without tadalafil treatment. The results indicated that the tadalafil-treated patients had a higher odds ratio (OR) of potency (adjusted OR = 2.58, 95% confidence interval [CI] = 1.28–5.22) than the nontadalafil-treated patients. However, those ≥65 years old were associated with a lower potency rate (adjusted OR = 0.94, 95% CI = 0.89-0.99). Conclusion: Starting penile rehabilitation with tadalafil 5 mg daily 1 month after nerve-sparing radical prostatectomy is safe for patients. Patients with mild-to-moderate ED should use tadalafil 5 mg daily after receiving nerve-sparing robotic-assisted laparoscopic prostatectomy due to its significant benefit in erectile function recovery.

Keywords: Impotency, prostatectomy, robotic

How to cite this article:
Lee IY, Tung MC, Hsu CY, Yin JH, Chang YK, Weng WC, Huang LH, Huang ZM, Yang CK, Ou YC. Effect of tadalafil on erectile function in patients after robotic-assisted radical prostatectomy with unilateral or bilateral nerve sparing. Urol Sci 2019;30:14-8

How to cite this URL:
Lee IY, Tung MC, Hsu CY, Yin JH, Chang YK, Weng WC, Huang LH, Huang ZM, Yang CK, Ou YC. Effect of tadalafil on erectile function in patients after robotic-assisted radical prostatectomy with unilateral or bilateral nerve sparing. Urol Sci [serial online] 2019 [cited 2023 Dec 1];30:14-8. Available from: https://www.e-urol-sci.com/text.asp?2019/30/1/14/246728

Introduction

The incidence of prostate cancer is rising throughout the world.^[1] Retropubic radical prostatectomy is still the “gold standard” for locally invasive disease.^[2] The da Vinci Robotic Surgical System has the benefit of technological advances, such as three-dimensional vision, 7 degrees of freedom, and magnification. Therefore, the use of robotic-assisted laparoscopic prostatectomy (RALP) has become more and more common.^[3] The advanced features of RALP have also provided radical prostatectomy with a better nerve-sparing (NS) capability.

Despite advances in surgical techniques, postoperative continence and potency rates are still not satisfactory.^[4],[5] To improve the potency rate, many clinical practitioners have used oral phosphodiesterase type-5 (PDE5) inhibitors or prostaglandin E1 injections for erection rehabilitation after nerve-sparing radical prostatectomy (NSRP).^[6],[7] Significant improvement in the potency rate of patients using PDE5 inhibitors for erection rehabilitation after undergoing NSRP has been reported.^[6] Wang et al. reviewed randomized controlled trials on the use of PDE5 inhibitors in patients with erectile dysfunction (ED) following radical prostatectomy. They reported greater efficacy among patients with mild ED that underwent a longer duration of treatment with a higher dosage.^[6] Tadalafil used daily was most effective in achieving drug-assisted erectile function (EF) among men with ED following NSRP.^[8] This suggested a potential role for tadalafil once daily in the recovery of EF after prostatectomy, provided it is used soon after surgery, and a possible role in protecting against both penile length loss and structural cavernosal changes after NSRP.^[8],[9] The majority of studies have focused on preoperatively potent patients and those who underwent bilateral neurovascular bundle (NVB)-sparing radical prostatectomy. In our previous study involving 41 preoperatively potent patients who received NS-RALP at a mean follow-up of 18 months, the potency rate was 86.4% for those undergoing bilateral NVB-preserving RALP and 52.5% for those undergoing unilateral NVB-preserving surgery.^[10] Later, Ou et al. reported that of 94 patients and 230 potent patients who received bilateral NVB-preserving RALP, 87.2% and 86.1%, respectively, were potent after RALP.^[11],[12] Of these patients, 41.6% were treated with PED5 inhibitors and 58.4% without.^[11] In our previous study, we used different PED5 inhibitors and different treatment protocols. For this study, we assessed the results of patients who received unilateral or bilateral NVB and of mild ED patients after using the same PED5 inhibitors. The purpose of this study was to evaluate whether early initiation of 5 mg tadalafil once daily provided a benefit in medicine-assisted erectile rehabilitation after NS-RARP in Taiwan.

Patients and Methods

Patients

Male patients aged 75 years or younger with mild-to-moderate ED or potency preoperatively, and who underwent unilateral or bilateral NS-RARP by the same surgeon, were collected from January 2013 to December 2014 at Tungs' Hospital. Inclusion criteria were a prostate-specific antigen (PSA) level <20 ng/mL, and no cardiovascular disease, uncontrolled hypertension, diabetes mellitus, Peyronie's disease, or a history of PDE5 inhibitor treatment. The RALP procedure has been previously described.^[10],[11] In the end, 163 patients were included in the study. To compare the potency of tadalafil, we divided the patients into two groups: those with and those without tadalafil treatment. The flow chart of the present study is shown in [Figure 1]. The data were collected prospectively, after the protocol had been approved by the Institutional Review Board of Tungs' Taichung MetroHarbor Hospital in Taiwan (106062). We did not exclude patients who had preoperative ED. The NS technique was performed using a modified prostatic fascia preservation (veil of Aphrodite) method.^[13]

Figure 1: Flowchart of patient selection

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Outcome

We collected clinical parameter data including body height, body weight, body mass index (BMI), age, American Society of Anaesthesiologists (ASA), PSA, Gleason score, prostate volume, and preoperative International Index of Erectile Function (IIEF-5) score.^[14] One month after operation, 5 mg tadalafil once daily was prescribed for patients whose Foley's catheter had been removed and who had ED. We recorded up to the 12^th month after surgery. We defined postsurgery IIEF-5 ≥22 as potency or no ED. We compared the correlation between clinical parameters and ED or no ED. The aim of the study was to assess the outcome and feasibility of tadalafil and nontadalafil treatment.

Statistical analysis

The mean (standard deviation [SD]), median (range), and count (percentage) were used to present the descriptive statistics, as appropriate. The IIEF-5 scores were recorded before prostatectomy (denoted as IIEF-5_pre) and at follow-up at the 12^th month after prostatectomy. The postsurgery potency (or EF recovery) rate was identified using the difference in IIEF-5_1y to IIEF-5_pre. The postsurgery potency rate at the 12^th month (denoted as P_6m) was defined as the proportion of patients with IIEF-5 scores ≥22. Those patients without EF recovery at the 6^th month were followed up to a year. The postsurgery potency rate at 1 year was defined as the proportion of patients with decreases of no <−4. The Chi-square test, t-test, and Fisher's exact test were used to assess the bivariate association, as appropriate. Multiple logistic regression analysis with the step-wise selection procedure was used to evaluate comparisons of the postsurgery potency rate between the groups with and without tadalafil treatment and relative covariates. P < 0.05 was considered a statistically significant association. The results are presented as odds ratio (OR), 95% confidence interval (95% CI), and P value. All the analyses were performed using SAS (statistic analysis system) version 9.13, SAS institute Inc, USA.

Results

The postsurgery potency rates of the study participants with and without tadalafil treatment were 55.6% and 32.1%, respectively. The mean (SD) of IIEF-5_pre for the with and without groups was 21.3 (4.5) and 19.2 (4.2), respectively. The potency rate and mean (SD) of IIEF-5_pre were both significantly different between the two groups (P = 0.004 and P = 0.005, respectively) [Table 1]. The baseline clinical condition parameters of the patients treated with or without tadalafil with potency are listed in [Table 2]. At the 12-month follow-up observation, there were no significant differences in baseline clinical condition parameters between these two groups. The OR of postpotency rates at 1 year based on logistic regression analysis of associated risk factors are shown in [Table 3]. In the multiple logistic regression model, the results indicated that the tadalafil treatment group had a higher OR of potency than the nontadalafil treatment group (adjusted OR = 2.58, 95% CI = 1.28–5.22). However, patients ≥65 years old had a significantly lower potency rate (adjusted OR = 0.94, 95% CI = 0.89–0.99) than those <65 years old. The other variables (prostate volume, ASA, and BMI) listed in [Table 3] showed no significant association with potency rate.

Table 1: Characteristics of the case and control subjects

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Table 2: Comparison of characteristics between case and control groups with postsurgery potency after one year of follow-up

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Table 3: Odds ratio of postsurgery potency based on a multiple logistic regression model for associated risk factors

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Discussion

PDE5Is effect on penile rehabilitation

This study was an important clinical trial, in that we could evaluate EF after NS-RARP and assess the relationship between clinical parameters and postoperative EF in Taiwan. Patients in our study with mild-to-moderate ED had a good postoperative outcome. However, patients with preoperative ED were not excluded from our study. Preoperative ED may have been due to the transrectal ultrasound prostate biopsy, distress due to the prostate cancer diagnosis, or anxiety about the surgery. Some studies have revealed an unsatisfactory postoperative potency rate – in one study, only 20% had returned to a preoperative EF status at postoperative 12 months.^[5] We wanted to improve this situation and have attempted to develop penile rehabilitation programs. Montorsi et al. did not meet their primary objective of using early initiation of tadalafil 5 mg once daily or 20 mg on demand to treat EF. After 9 months of medicine use and a 6-week drug washout, neither tadalafil 5 mg once daily nor 20 mg on demand showed benefit over a placebo in treating unassisted EF. The following 4-week open-label 5 mg tadalafil once daily regimen provided a benefit for assisted EF and reduced penile length loss to a greater extent than 20 mg tadalafil on demand or a placebo.^[8] At the very least, the use of tadalafil for assisted erectile rehabilitation is safe and feasible. Previous data have shown increasing fibrosis of the penis over time and ED postoperatively.^[15] The aims of penile rehabilitation are to minimize the fibrosis of the smooth muscle and venous leakage of the corpora cavernosa and to maximize opportunities to return to a preoperative EF status.^[16] PDE5Is recently have become the most popular first-line agent for penile rehabilitation. Several basic trials have shown the functional and histological benefits of PDEIs use after penile rehabilitation in animal models.^{[17],[18],[19],[20]} However, this effect has not been observed in humans. Briganti et al. suggested that clinical parameters will influence the effect of penile rehabilitation.^[21] In their study, 435 men with postbilateral NSRP were divided into groups based on their risk of ED postoperatively: low (age <65 years or IIEF-5 = 26 or CCI <1 [n = 184]), intermediate (age 66–69 years or IIEF-5 = 11–25 or CCI >1 [n = 115]), and high (age >70 years or IIEF-5 <10 or CC >2 [n = 136]). Of the 435 men, 193 did not use PDE5Is after surgery, 147 took on-demand PDE5Is and 95 received PDE5Is daily or every other day. The potency rate was higher among those who used any type of PDE5Is than among those who received no treatment. The possible reasons for the great variation in reported potency rates (54%–94%)^[22] were the different preoperative IIEF-5 scores, definitions of postoperative potency, penile rehabilitation agents, and surgical techniques. The same da Vinci Robotic Surgical System, as well as the same surgical procedure and fixed penile rehabilitation program by the same surgeon, was used for the patients in our study.

Erectile function recovery in our study

Other studies have concluded that age and preoperative IIEF-5 score were predictors of the postoperative potency rate.^[23],[24] However, the clinical parameters of age and preoperative IIEF-5 score did not significantly influence the postoperative potency rate 12 months after operation in our study. The patients included in our study received tadalafil 5 mg daily for at least 1 year and the postsurgery potency rates at the 12^th month were 55.6%, overall.

Nerve protection during surgery

During our surgical procedure, we used Weck Hem-o-Lok Clip (Teleflex Incorporated, NC, USA) instead of electrocauterization for NVB dissection, to prevent thermal injury to the cavernous nerves. However, athermal studies have reported inconsistent results.^[25],[26]

Menon et al. reported that the prostatic fascia preservation (veil of Aphrodite) technique appears to have enhanced the quality of nerve preservation, avoiding neurovascular injury after robotic prostatectomy, and resulting in potency rates of 97% at the 1-year follow-up.^[13]

A traction-free technique was suggested recently to prevent neuropraxia. In spite of the statistical insignificance, the results of our study indicated that patients that underwent surgery at Tungs' Hospital or who had a BMI under 24 kg/m² were associated with a lower potency rate. We proposed that more fat tissue may protect against neuropraxia due to traction injury. More studies on the cavernous nerve protection during NVB dissection to provide greater opportunities for potency recovery should be performed in the future.

Side effects

The side effects of tadalafil use include backache, headache, dyspepsia, myalgia, cough, and nasal congestion. The most common are headache and dyspepsia. Only two patients in our study had these side effects. One had headache and the other had backache after taking tadalafil for 6 months. Other patients had no side effects after taking tadalafil for >1 year.

Conclusion

In conclusion, starting penile rehabilitation with tadalafil 5 mg daily 1 month after NSRP is safe for patients. Patients with mild-to-moderate ED before receiving NS-RALP should use tadalafil 5 mg daily after surgery due to its significant benefit for EF recovery. Based on our study results, this medical treatment should be maintained for >1 year. More studies are needed to evaluate suitable durations of treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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