The timing of penile rehabilitation after bilateral nerve‐sparing radical prostatectomy affects the recovery of erectile function

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To define if erectile function (EF) outcomes were better in men with early institution of penile rehabilitation after radical prostatectomy (RP), as one of the mechanisms by which patients fail to recover EF after RP is collagenization of corporal smooth muscle with subsequent venous leak development, and rehabilitation is aimed at preventing these structural alterations.

PATIENTS AND METHODS

The study population comprised patients who: (i) had clinically organ‐confined prostate cancer; (ii) had fully functional erections, corroborated by the partner; (iii) had bilateral nerve‐sparing RP; and (iv) committed to pharmacological penile rehabilitation. Patients completed the International Index of Erectile Function (IIEF) serially after RP. Patients were instructed to obtain three erections/week using initially sildenafil, and if unsuccessful, then intracavernous injections. Patients were subdivided into those starting rehabilitation at <6 months after RP (early) and those starting at ≥6 months after RP (delayed).

RESULTS

There were 48 patients in the early group and 36 in the delayed group; patients in both groups were matched for age, comorbidity status and baseline EF. The mean duration after RP at the time of starting penile rehabilitation was 2 and 7 months in the early and delayed groups, respectively (P < 0.01). At 2 years after surgery there was a highly statistically significant difference in IIEF EF domain score between the early and delayed groups (22 vs 16, P < 0.001). There were also statistically significant differences between the groups in the percentage of men at 2 years after RP who had unassisted functional erections and sildenafil‐assisted functional erections (58% vs 30%, P < 0.01; 86% vs 45%, P < 0.01, respectively).

CONCLUSIONS

These data suggest that delaying the start of penile rehabilitation after RP is associated with poorer outcomes for EF.     

Irbesartan promotes erection recovery after nerve‐sparing radical retropubic prostatectomy: a retrospective long‐term analysis

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction following radical prostatectomy (RP) is among the most common and dreaded adverse effects of the surgery. Multiple studies confirm the potential benefit of various drug classes to accelerate the return of erectile function (EF) after RP. There is pre‐clinical evidence supporting the use of angiotensin‐receptor blockers (ARBs) for this purpose, although this has not been studied in humans. The present study shows that there may be a benefit in the recovery of EF post‐RRP in patients taking a daily dose of irbesartan, an ARB, following RRP. In addition, the use of irbesartan may curb the loss of stretched penile length which occurs postoperatively. Further study in the form of prospective, randomized, placebo‐controlled clinical trials are necessary to confirm these findings.

OBJECTIVE

• ? To evaluate retrospectively the potential benefit of administering irbesartan, an angiotensin‐receptor blocker, to improve erectile function (EF) recovery after nerve‐sparing radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

• ? Before surgery potent patients who underwent nerve‐sparing RRP between April and December 2009 elected to start daily oral irbesartan 300 mg on postoperative day 1 (n= 17). A contemporaneously clinically matched cohort consisting of patients who declined irbesartan use served as the control group (n= 12).
• ? Postoperative ‘on demand’ use of erectile aids (phosphodiesterase type 5 [PDE5] inhibitors and intracavernous injections) was adopted.
• ? Potency was monitored by the administration of International Index of Erectile Function‐5 (IIEF‐5) questionnaires before surgery and at early (3 months) and long‐term (12 and 24 months) postoperative intervals.
• ? Stretched penile length (SPL) was measured both immediately and 3 months after surgery.

RESULTS

• ? EF status was no different between groups at baseline (P > 0.05).
• ? While the IIEF‐5 scores at 24 months after surgery were statistically similar between the two groups (control = 15.2 ± 2.0, irbesartan = 14.1 ± 3.1, P= 0.77), at 12 months the IIEF‐5 scores of the irbesartan group were significantly higher than those of the control group (14 ± 2.6 vs. 7.2 ± 1.6, P < 0.05).
• ? The proportional loss of SPL after RRP was less in the irbesartan than in the control group at 3 months (–0.9 ± 1.5% vs –5.6 ± 1.5, P < 0.05).

CONCLUSION

• ? Regular irbesartan use after nerve‐sparing RRP in patients with normal preoperative erectile function could improve EF recovery after surgery and mitigate early loss of SPL.

     

Efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors in treating erectile dysfunction after bilateral nerve‐sparing radical prostatectomy

We carried out a systematic review and meta‐analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve‐sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double‐blind, placebo‐controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co‐primary efficacy end points: International Index of Erectile Function‐Erectile Function (IIEF‐EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87–5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57–48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3–13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta‐analysis indicates that PDE5 inhibitors to be an effective and well‐tolerated treatment for ED after BNSRP.     

Role of sildenafil citrate in treatment of erectile dysfunction after radical retropubic prostatectomy

BACKGROUND: Sildenafil citrate was introduced as a treatment for erectile dysfunction in April 1998 in the United States and has been available since March 1999 in Japan. In this article, we assess the efficacy of sildenafil in the treatment of erectile dysfunction in Japanese men after radical retropubic prostatectomy for localized prostate cancer. METHODS: Of 106 men who underwent radical retropubic prostatectomy between January 1994 and March 2000, 43 were prescribed sildenafil at their request after radical retropubic prostatectomy. Medication was initiated at 25 mg, and if this was ineffective, the dose was increased to 50 mg. Of the patients, 18 underwent bilateral and 21 unilateral nerve sparing (NS) procedures, while in 4 patients, a non-NS procedure was performed. These patients were interviewed using a questionnaire about their response to sildenafil and using the 5-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Thirty-three of the 43 patients were eligible for evaluation of the efficacy of sildenafil and 27 completed the IIEF-5 questionnaires. Sildenafil at 50 mg had a better effect on sexual function than 25 mg in most Japanese patients. Of the 16 patients who underwent bilateral NS procedures, 10 (62.5%) had improved ability for intercourse and 3 (18.8%) had improved erections. Of the 13 patients who underwent unilateral NS procedures, 7 (53.8%) had improved ability for intercourse and 4 (30.8%) had improved erections. None of the 4 patients who underwent non-NS procedures had a positive response. Of 24 patients with positive response to sildenafil, 3 (12.5%) did not have to take sildenafil after receiving it because they did not require it for intercourse. Mean IIEF-5 score increased from 4.3 to 11.4 (P < 0.0001). Patient age, time since surgery, PSA and pathological stage did not have statistically significant effects on outcome. The most commonly cited adverse effect was headache (21%). CONCLUSION: Sildenafil is equally effective for erectile dysfunction in Japanese patients who have undergone bilateral and unilateral NS procedures, and aids recovery of natural erectile function after radical retropubic prostatectomy. However, non-NS procedure patients had no response to sildenafil. This study suggested that sildenafil is well tolerated and should be initially used for treatment of Japanese men with erectile dysfunction after radical retropubic prostatectomy.     

The science of vacuum erectile device in penile rehabilitation after radical prostatectomy

Introduction

Radical prostatectomy (RP) is a standard surgical treatment for clinically localized prostate cancer. Erectile dysfunction (ED) and penile shrinkage are common complications. Vacuum Erectile Device (VED) therapy uses negative pressure to distend the corporal sinusoids and to increase blood inflow into the penis. It is the second most commonly used method for penile rehabilitation after RP. However, the underlying mechanisms are still unclear. This paper is designed to review the scientific evidences of VED therapy after RP and discuss the possible mechanisms.

Methods

We reviewed published papers of post-prostatectomy penile rehabilitation using VED. We analyzed the scientific evidences of VED therapy and discussed the possible underlying mechanisms.

Results

There are existing clinical evidences for VED therapy to improve ED and preserve penile size. Emerging basic scientific evidence is available and further study is still needed to understand the mechanisms at the molecular level.

Conclusions

Current clinical evidences support the safety, tolerability, effectiveness and benefits of early VED therapy after RP. The available basic scientific evidences demonstrate that VED therapy for penile rehabilitation is achieved by increasing arterial inflow, anti-apoptotic, anti-fibrotic and anti-hypoxia mechanisms.     

Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil

BACKGROUND: We retrospectively evaluated the erectile function after nerve-sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between January 1996 and December 2001. Erectile function following nerve-sparing RRP was assessed by a simple mailed questionnaire that was constructed for the study. RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but for 12, function was not sufficient to penetrate. The overall estimated recovery rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months. However, that of erection sufficient to penetrate was only 17.7% at 36 months and was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9 of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were divided according to preoperative erectile function, no difference was found in the efficacy rate between patients with normal function and those with ED. CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a sufficient erection. However, sildenafil is effective for ED following nerve-sparing RRP regardless of the nerve-sparing procedure or preoperative erectile function. Thus, preoperative function alone, although depending on its severity, may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if patients want to have the operation.     

Penile rehabilitation after radical prostatectomy: what the evidence really says

The pathophysiology of erectile dysfunction after radical prostatectomy (RP) is believed to include neuropraxia, which leads to temporarily reduced oxygenation and subsequent structural changes in penile tissue. This results in veno‐occlusive dysfunction, therefore, penile rehabilitation programmes focus on tissue oxygenation. Animal studies support the use of phosphodiesterase type 5 inhibitors (PDE5Is) after cavernous nerve damage but results from human studies are contradictory. The largest study to date found no long‐term effect of either daily or on‐demand PDE5I administration after RP compared with placebo. The effects of prostaglandin and vacuum erection devices are questionable and high‐quality studies are lacking. Better documentation for current penile rehabilitation and/or better rehabilitation protocols are needed. One must be careful not to repeat the statement that penile rehabilitation improves erectile function after RP so many times that it becomes a truth even without the proper scientific backing.     

The effects of phosphodiesterase type 5 inhibitors on penile rigidity variables during a period with no sexual stimulation: a laboratory setting double‐blind study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? There is a positive effect of PDE5 inhibitors on several aspects of the men’s sex lives, chiefly erectile function, personal self‐esteem, and satisfaction from their sex lives. To our knowledge, our study is the first study to evaluate the effects of PDE5 inhibitors on erectile variables simultaneously in a laboratory setting. In the present study, significant penile rigidities were obtained with PDE5 inhibitors in a short period, with no sexual stimulation, in laboratory conditions. Our findings might support the use of PDE5 inhibitors in the men who need penile rehabilitation.

OBJECTIVE

To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double‐blind study.

PATIENTS AND METHODS

In all, 80 men without erectile dysfunction (ED) but with lifelong premature ejaculation (PE) were included in the study. The men were divided equally in to four groups and received either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. The men attended the laboratory following 3 days of sexual abstinence and placebo or one of the PDE5 inhibitors was ingested after ≥2 h of fasting and non‐smoking. The men were then immediately placed in a silent room and real‐time penile rigidity and tumescence monitoring with Rigiscan Plus (Rigiscan Plus® System, Osbon Medical Systems, Augusta, GA, USA) began. The men read some magazines or newspapers that contained no sexually stimulating material for 1.5 h. There was no interaction between the men and observer during the test period. Times to first measured and total durations of base and tip rigidities, and also total and per minute rigidity were evaluated.

RESULTS

The recorded base and/or tip rigidity ratios were 40% (eight of 20), 71% (12/17), 47% (nine of 19) and 70% (14/20) in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.126). The ratio of men who could obtain ≥60% base and/or tip rigidities were 10% (two of 20), 41% (seven of 17), 26% (five of 19) and 55% (11/20) in placebo, sildenafil, tadalafil and vardenafil groups, respectively (P < 0.05). The median time to first measured base rigidity was 58.0, 21.5, 54.5 and 57 min with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0032). The median total duration of recorded base rigidity was 4.0, 27.5, 10.0 and 11.5 min in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.013). The median total base rigidity (area under the curve) was 72.8, 699.0, 360.5 and 553.0 with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.016).

CONCLUSIONS

Significant penile rigidities were obtained with PDE5 inhibitors during the short test period, with no sexual stimulation, in laboratory conditions. This finding might support the use of PDE5 inhibitors in men who need penile rehabilitation.     

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre,randomized, double‐blind,placebo‐controlled trial

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED). Preclinical and clinical phase I studies showed that avanafil had enhanced selectivity, faster onset of action and a favourable side‐effect profile relative to currently available PDE5 inhibitors. As the result of phase III clinical trial for the efficacy and safety of avanafil treatment (100 and 200 mg), taken as needed over a period of 12 weeks, in Korean patients with ED, avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.

OBJECTIVE

• ? To evaluate the efficacy and safety of avanafil, a new potent selective phosphodiesterase type 5 (PDE5) inhibitor, in patients with erectile dysfunction (ED).

PATIENTS AND METHODS

• ? The present study was a multicentre, randomized, double‐blind, placebo‐controlled, fix‐dosed phase three clinical trial involving 200 patients with ED.
• ? The subjects were treated with placebo or avanafil (100 or 200 mg) for 12 weeks and were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ).
• ? The primary outcome variable was the change from baseline for IIEF erectile function domain (EFD) score.
• ? The secondary outcome variables were SEP Q2 and Q3, the shift to normal rate (EFD ≥ 26), and response to the GAQ.

RESULTS

• ? Compared with placebo, patients who took 100 or 200 mg of avanafil had significantly improved IIEF‐EFD score.
• ? There were similar results when comparing Q2 and Q3 in the SEP diary and the GAQ.
• ? Flushing was the most common treatment‐related adverse event.
• ? Most adverse events were transient and mild or moderate in severity.

CONCLUSION

• ? Avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.

     

Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

Erectile dysfunction （ED） is a major complication after radical prostatectomy （RP）; however, debatecontinues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function （EF）. This study includeda total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 （46.6%） of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation （60.0%） was significantly greater than that in those without penile rehabilitation （38.2%）. Of several parameters examined, the preoperative International Index of Erectile Function-5 （IIEF-5） score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP.     

负压勃起装置治疗前列腺癌根治术后的勃起功能障碍

目的:探讨负压勃起装置(VED)治疗前列腺癌根治术(RP)后勃起功能障碍(ED)的有效性和安全性。方法:开放性RP术后ED患者6例,3例于术后3个月内(A组),3例于术后12个月以上(B组)分别进行VED康复治疗,比较两组在VED治疗前,治疗后3个月和6个月的IIEF-5评分的差异,治疗6个月后的阴茎长度和周径变化的差异。评价VED应用的安全性,以及患者和性伴侣的满意度。结果:6例患者VED治疗后3个月和6个月的IIEF-5平均评分均较治疗前提高(P<0.05)。A组患者VED治疗后3个月IIEF-5评分(8.7±0.6)分,治疗后6个月IIEF-5评分(13.0±1.0)分,均高于B组患者[(6.7±0.6)分;(8.3±1.5)分](P<0.05)。VED治疗后6个月,A组患者阴茎长度缩短(0.4±0.1)cm,周径缩短(0.2±0.1)cm,B组患者阴茎长度缩短(1.7±0.4)cm,周径缩短(0.9±0.3)cm,两组相比均有显著差异(P<0.05)。VED治疗后6个月的患者及性伴侣性生活满意率分别为83.3%和50.0%。VED治疗期间,1例患者诉阴茎皮肤发暗,2例诉性交僵硬麻木感,其余无明显不良反应。结论:RP术后ED患者早期进行VED康复治疗,能显著改善勃起功能,减少阴茎萎缩。     

Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil

OBJECTIVE

To evaluate the effect of low‐dose sildenafil for rehabilitating erectile function after nerve‐sparing radical prostatectomy (NSRP), as the delay to recovery of erectile function after NSRP remains under debate.

PATIENTS AND METHODS

Forty‐three sexually active patients had a NSRP; at 7–14 days after surgery they had a Rigiscan® (Dacomed Corporation, Minneapolis, MN, USA) measurement of nocturnal penile tumescence and rigidity (NPTR). To support the recovery of spontaneous erectile function, 23 patients with preserved nocturnal erections received sildenafil 25 mg/day at night. A control group of 18 patients were then followed but had no phosphodiesterase‐5 inhibitors. The International Index of Erectile Function (IIEF)‐5 questionnaire was completed 6, 12, 24, 36 and 52 weeks after NSRP.

RESULTS

Of the 43 patients, 41 (95%) had one to five erections during the first night after catheter removal. In the group using daily sildenafil the mean IIEF‐5 score decreased from 20.8 before NSRP to 3.6, 3.8, 5.9, 9.6 and 14.1 at 6, 12, 24, 36 and 52 weeks after NSRP, respectively. In the control group the respective scores were 21.2, decreasing to 2.4, 3.8, 5.3, 6.4 and 9.3. There was a significant difference in IIEF‐5 score and time to recovery of erectile function between the groups (P < 0.001), with potency rates of 86% vs 66%.

CONCLUSION

The measurement of NPTR after NSRP showed erectile function even the ‘first’ night after catheter removal. In cases of early penile erection, daily low‐dose sildenafil leads to a significant improvement in the recovery of erectile function.     

Generating comprehensive comparative evidence on various interventions for penile rehabilitation in patients with erectile dysfunction after radical prostatectomy: a systematic review and network meta-analysis

BackgroundWe aim to present a comprehensive comparison of various treatments in the management of penile recovery after radical prostatectomy (RP) and provide recommendations for future research.MethodsLiterature search of electronic databases including PubMed, the Cochrane Library, Embase, PsycInfo, and Web of Science, and manual retrieval were conducted from inception through March 2020. “Erectile dysfunction” and “prostatectomy” were used as the Mesh terms. The patients, intervention, comparison, outcome, and study design (PICOS) approach were used to define study eligibility. Two authors independently selected studies, evaluated the methodological quality, and extracted data using Cochrane Collaboration’s tools. The data analysis was completed by STATA version 14.2.ResultsA total of 24 studies with 3,500 patients were incorporated in the final analysis after screening 6,131 records. Our findings indicated that vacuum constriction devices (VCD) ranked 1st which meant that patients in VCD group had the best effect regarding mean IIEF scores within 3 months after RP, and no significant difference was observed between VCD and VCD with 20 mg/day tadalafil (V20DT) (MD: 5.44; 95% CI: −0.81 to 11.69). VCD and 50 mg/day sildenafil (VC50DS) showed superiority over 50 mg/day sildenafil (50DS) (MD: 3.75; 95% CI: 2.74–4.76) and intraurethral alprostadil 125–250 µg (MD: 3.05; 95% CI: 0.38 to 5.72), respectively. Moreover, V20DT showed significant superiority over the other interventions for ≥6 months mean International Index Erectile of Function (IIEF) scores after RP. Monotherapy appeared to have similar efficacy in terms of mean IIEF scores and proportion of patients return to baseline, and the effect of phosphodiesterase type 5 inhibitors (PDE5is) did not seem to be affected by the patterns of administration (regular or on demand).ConclusionsThe combination therapy showed certain advantages over monotherapy, and we recommended the combination of VCD and PDE5is to be considered in the clinical management of penile rehabilitation after RP.