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A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy.

ABSTRACT:

Background

Although the concept of penile rehabilitation after radical prostatectomy (RP) has been advocated for decades, there is little definitive evidence regarding its utility or the best strategy to optimize patient outcomes.

Aim

The goal of this study is to analyze the ability of 3 different pharmacological strategies to preserve the ability of men to achieve spontaneous (non-medication assisted) erections after bilateral nerve-sparing RP.

Methods

This IRB- and FDA-approved study studied penile rehabilitation in a 3-arm fashion with a target enrollment of 200 patients. (i) Control arm: nightly placebo with sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (ii) nightly sildenafil arm: nightly sildenafil 50 mg and sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (iii) combination therapy arm: nightly sildenafil 50 mg (5 nights/week) plus intracavernosal injections twice/week. Inclusion criteria included bilateral nerve-sparing surgery, normal serum total testosterone, and good preoperative baseline erectile function as measured by the erectile function domain score of the IIEF (EFD) (≥24). Patients were followed with a medication use diary and the IIEF questionnaire at 6 weeks, 3 m, 6 m, 12 m, 18 m and 24 m.

Outcomes

A difference was seen in the IIEF-EFD scores between the 3 groups at 24 months after RP. Secondary end points include the time to return of spontaneous functional erections, the time for patients to respond to oral erectogenic therapy, and the proportion of patients who have normalization of their IIEF-EFD scores.

Results

The study was interrupted because of failure to recruit the target study population in a reasonable timeframe. A total of 76 subjects with median age of 57 (IQR: 51, 63) years and mean IIEF-EFD of 29 (IQR: 27, 30) were initially randomized, but at 24 months, the sample sizes by group were (i) n = 4; (ii) n = 18; and (iii) n = 10, with median IIEF-EFD 24 (IQR: 18, 28), 24 (IQR: 18, 28), and 21 (IQR: 9, 26), respectively. There was no statistical difference among the groups in the final analysis.

Clinical implications

Definitive evidence for the ability of different pharmacological rehabilitation strategies to improve long-term EF outcomes might never be available.

Strengths & limitations

This was a well-designed randomized and 3-arm designed trial intended to provide decisive evidence regarding the utility of penile rehabilitation. Failure to recruit the target population is the main limitation.

Conclusion

The limited number of patients in the present trial precludes definitive interpretation. However, results indicate how challenging it is to conduct true rehabilitation studies. Miranda EP, Benfante N, Kunzel B, et al. A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy. J Sex Med 2021;18:423-429.

SUBMITTER: Miranda EP

PROVIDER: S-EPMC8519168 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP).The present study was conducted between July 2010 and March 2013 as a randomized prospective trial at two university hospitals. Eligible participants were continent men with an International Index of Erectile Function-5 (IIEF-5) score of at least 18, scheduled to undergo nerve-sparing RP. Patients were randomized to a PVS group or a control group. Patients in the PVS group were instructed in using a PVS device (FERTI CARE(®) vibrator). Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks. Participants were evaluated at 3, 6 and 12 months after surgery with the IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at http://clinicaltrials.gov/ (NCT01067261).Data from 68 patients were available for analyses (30 patients randomized to PVS and 38 patients randomized to the control group). The IIEF-5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance. At 12 months, 16/30 (53%) patients in the PVS group had reached an IIEF-5 score of at least 18, while this was the case for 12/38 (32%) patients in the control group (P = 0.07). There were no significant differences in the proportions of continent patients between groups at 3, 6 or 12 months. At 12 months 90% of the PVS patients were continent, while 94.7% of the control patients were continent (P = 0.46).The present study did not document a significant effect of PVS. However, the method proved to be acceptable for most patients and there was a trend towards better erectile function with PVS. More studies are needed to explore this possible effect further.

Project description:BackgroundsConsidering the natural course of cavernous nerve recovery after robot-assisted laparoscopic prostatectomy (RALP), early intervention of low intensity extracorporeal shock wave therapy (LIESWT) would be more effective for enhancing overall recovery of sexual function (SF). Our objective of this study is to analyze longitudinally the alterations of SF in patients after RALP, with a focus on the effect of early and delayed intervention with LIESWT.MethodsA total of 5 and 11 patients underwent early and delayed intervention with LIESWT, respectively. SF was assessed with the Expanded Prostate Cancer Index Composite (EPIC). The same surgeon performed RALP on 178 patients, and these patients were assigned to the non-LIESWT group to establish a control group. The SF score of EPIC was investigated longitudinally before RALP and 3, 6, 9, and 12 months after RALP.ResultsOur results show that penile rehabilitation with LIESWT immediately before urethral catheter removal improved SF scores. In the baseline, the SF score was significantly higher in the early LIESWT group (P=0.0001). The SF score was significantly lower at postoperative 6 months (early 19.2, delayed 17.9, and non-LIESWT 8.1; P=0.0171), 9 months (20.9, 25.8, and 10.2; P=0.0188), and 12 months (28.0, 21.3, and 9.5; P=0.0051) in the non-LIESWT group. We regret that there was no significant difference in the recovery of SF between the early and delayed protocol with LIESWT at all points. In keeping with our results, LIESWT demonstrated the potential to be efficacious in treatment options for severe post-radical prostatectomy (RP) erectile dysfunction (ED) as it may indirectly support its promotion of nerve regeneration in severe ED due to RP.ConclusionsThis is the first study in which LIESWT has been shown to deliver a clinical benefit on its early or delayed intervention to patients after RALP to penile rehabilitation in terms of restoring SF. Our preliminary results suggest that LIESWT could be used as a treatment option in penile rehabilitation.

Project description:INTRODUCTION:Despite the importance of using penile injections as part of a penile rehabilitation program, men have difficulty complying with these programs. AIM:To test a novel psychological intervention based on Acceptance and Commitment Therapy for erectile dysfunction (ACT-ED) to help men utilize penile injections. METHODS:This pilot randomized controlled trial (RCT) recruited men who were beginning a standard care (SC) structured penile rehabilitation program following radical prostatectomy. The SC program instructed patients to use penile injections 2 to 3 times per week. Participants were randomized to SC+ACT-ED or SC+enhanced monitoring (EM). Over 4 months, patients in the SC+ACT-ED group received SC plus 4 ACT sessions and 3 ACT phone calls; those in the EM group received SC plus 7 phone calls from an experienced sexual medicine nurse practitioner. Participants were assessed at study entry and at 4 and 8 months. For this pilot study, the goal was to determine initial efficacy (ie, effect sizes, where d = 0.2 is small, d = 0.5 is medium, and d = 0.8 is large). MAIN OUTCOME MEASURE:Primary outcomes were feasibility and use of penile injections. Secondary outcomes were ED treatment satisfaction (ie, Erectile Dysfunction Inventory of Treatment Satisfaction, or EDITS), sexual Self-Esteem and Relationship (SEAR) quality, sexual bother (SB), and prostate cancer treatment regret. RESULTS:The 53 participants were randomized (ACT, n = 26; EM, n = 27). The study acceptance rate was 61%. At 4 months, the ACT-ED group utilized more penile injections per week (1.7) compared to the EM group (0.9) (d = 1.25; P = .001) and was more adherent to penile rehabilitation compared to the EM group (ACT, 44%; EM, 10%; relative risk [RR], 4.4; P = .02). These gains were maintained at 8 months for injections per week (ACT, 1.2; EM, 0.7; d = 1.08; P = .03) and approached significance for adherence (ACT, 18%; EM, 0%; P = .10). At 4 months, ACT-ED, compared to EM, reported moderate effects for greater satisfaction with ED treatment (d = 0.41; P = .22), greater sexual self-esteem (d = 0.54; P = .07) and sexual confidence (d = 0.48; P = .07), lower sexual bother (d = 0.43; P = .17), and lower prostate cancer treatment regret (d = 0.74; P = .02). At 8 months, moderate effects in favor of ACT-ED were maintained for greater sexual self-esteem (d = 0.40; P = .19) and less treatment regret (d = 0.47; P = .16). CLINICAL IMPLICATIONS:ACT concepts may help men utilize penile injections and cope with the effects of ED. STRENGTHS AND LIMITATIONS:Strengths include use of an innovative intervention utilizing ACT concepts and pilot RCT. Limitations include the pilot nature of the study (eg, small samples size, lack of statistical power). CONCLUSION:ACT-ED is feasible and significantly increases the use of penile injections. ACT-ED also shows promise (moderate effects) for increasing satisfaction with penile injections and sexual self-esteem while decreasing sexual bother and prostate cancer treatment regret. Nelson CJ, Saracino RM, Napolitano S, et al. Acceptance and Commitment Therapy to Increase Adherence to Penile Injection Therapy-Based Rehabilitation After Radical Prostatectomy: Pilot Randomized Controlled Trial. J Sex Med 2019; 19:1398-1408.

Project description:Radical prostatectomy (RP) offers a good long-term cancer control for clinically localized prostate cancer. However, complications such as erectile dysfunction and substantial decreases quality of life of the afflicted men and their sexual partners. Identification of pre-, per-, and postoperative factors that correlate with poor postoperative erectile status must be considered an important step to improving penile rehabilitation.To describe postoperative erectile function after RP in a Danish cohort.The medical records of 1,127 patients undergoing RP from March 2003 through September 2014 were reviewed retrospectively with a 12-month follow-up after surgery. In all, 704 patients fulfilling the inclusion criteria were included in the final analysis. Recovery was defined as self-reported erection sufficient for intercourse (ESI) with or without usage of erectile aids.Subjective reporting of erectile function and usage erectile aids 12 months after RP.ESI with or without erectile aids was reported by 226 men (32.1%), among whom 109 (48.2%) required erectile aids. Erectile dysfunction (ED) was reported by 478 men (67.9%) and by 121 (25.3%) despite use of erectile aids. Of men with ED, 155 (22%) stated not being interested in penile rehabilitation, 26 (3.7%) stated not having resumed their sex life 12 months after RP, and 241 (34.2%) had ED and were unsatisfied with the condition. We found that 134 of 445 men (30.1%) who underwent non-nerve-sparing RP had ESI 12 months after RP. Age older than 60.5 years, a high body mass index, comorbidity, and a high American Society of Anesthesiologists score were negative predictors of erectile function 12 months after RP.Twelve months after RP, 32.1% of men had ESI; half these men required the use of erectile aids. Age older than 60.5 years, a high body mass index, comorbidity, and a high American Society of Anesthesiologists score were negative predictors for ED 12 months after RP. Haahr MK, Azawi NH, Andersen LG, et al. A Retrospective Study of Erectile Function and Use of Erectile Aids in Prostate Cancer Patients After Radical Prostatectomy in Denmark. Sex Med 2017;5:e156-e162.

Project description:BACKGROUND:The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery. OBJECTIVE:We examined whether these practice changes have led to observed improvements in EF rates over time. DESIGN, SETTING, AND PARTICIPANTS:We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008-2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered. INTERVENTION:EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ?24. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery. RESULTS AND LIMITATIONS:We observed a significant decrease over time of the EF recovery rates at both 12 and 24mo post-RP (all p=0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p<0.01), with a resultant increase in risk of comorbidity (odds ratio [OR]=1.1, 95% confidence interval [CI]: 1.02-1.15; p=0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p=0.0003). After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12mo: OR=0.97, 95% CI: 0.91-1.03, p=0.4; 24mo: OR=0.97, 95% CI: 0.91-1.03, p=0.3). CONCLUSIONS:Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP. PATIENT SUMMARY:The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy.

Project description:ObjectiveTo investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF).DesignSystematic review and meta-analysis.MethodsA systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Included were original studies performed on humans assessing ED after PRF according to the 5-item International Index of Erectile Function (IIEF-5) questionnaire and fracture classification following Young and Burgess, Tile or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association. Furthermore, interventional cohort studies assessing the effect of penile rehabilitation therapy with phosphodiesterase-5-inhibitors (PDE-5-I) on IIEF-5 scores compared before and after treatment were included. Results were presented as forest plots of proportions of patients with ED after PRF or mean changes on IIEF-5 questionnaires before and after penile rehabilitation. Studies not included in the quantitative analysis were narratively summarised. Risk of bias assessment was conducted using the revised tool for the Quality Assessment on Diagnostic Accuracy Studies.ResultsThe systematic literature search retrieved 617 articles. Seven articles were included in the qualitative analysis and the meta-analysis. Pooled proportions revealed 37% of patients with ED after suffering any form of PRF (result on probability scale pr=0.37, 95% CI: 0.26 to 0.50). Patients after 3 months of penile rehabilitation therapy reported a higher IIEF-5 score than before (change score=6.5 points, 95% CI: 2.54 to 10.46, p value=0.0013).ConclusionDespite some heterogeneity and limited high-quality research, this study concludes that patients suffering from any type of PRF have an increased risk of developing ED. Oral intake of PDE-5-I for the purpose of penile rehabilitation therapy increases IIEF-5 scores and may relevantly influence quality-of-life in these patients.Prospero registration numberCRD42020169699.