Management of erectile dysfunction following radical prostatectomy

Radical prostatectomy is the standard treatment for organ/ specimen-confined prostate cancer, yet erectile dysfunction in selected series is still reported as high as 90% after this procedure. Thus, most men need adjuvant treatments to be sexually active following radical prostatectomy. These include vacuum constriction devices, intracorporeal injections of vasoactive drugs, and transurethral dilators, all of which have reported response rates of 50% to 70%. Unfortunately, long-term compliance is suboptimal, with a discontinuation rate of nearly 50% at one year. These non-oral options should be offered on an individual basis to patients who have failed oral therapy since efficacy and compliance vary. Also, these options should be considered in the early postoperative period to enhance sexual activity and penile oxygenation, which may prevent corporeal fibrosis. Early penile rehabilitation with intracavernosal injections or vacuum constriction devices should be encouraged to increase chances for recovery of rigid erections. In patients with some preservation of nerve tissue, oral sildenafil may be effective in promoting an earlier return of erectile function. The potential impact of sildenafil and other new oral therapies should encourage urologists to continue to perform and perfect the nerve-sparing approach.     

Strategies to promote recovery of cavernous nerve function after radical prostatectomy

While the application of penile autonomic nerve-sparing techniques during radical prostatectomy for clinically localized prostate cancer has improved erection recovery rates after surgery, many men still experience delayed or incomplete recovery of erectile function. In recognition of neuropathy as a likely basis for erectile dysfunction after radical prostatectomy, investigators have begun exploring new strategies to promote the functional recovery of nerves responsible for penile erection in the course of this management. Primary efforts continue for preserving the integrity of the penile nerves, while the next frontier in clinical management has encompassed strategies directed toward maximally restoring their function. Such strategies include cavernous nerve interposition grafting and neurotrophic treatments that meet nerve reconstructive and nerve regenerative objectives, respectively. Early successes with both innovations preclinically and clinically suggest their feasibility and potential roles to reduce the incidence of erectile dysfunction after radical prostatectomy. The purpose of this report is to review strategies under development to promote post-prostatectomy erectile function, particularly with respect to preserving penile innervation involved in this function.     

机器人辅助腹腔镜前列腺癌根治术后性功能恢复的研究进展

前列腺癌(Prostate cancer,PCa)现已成为老年男性常见的恶性肿瘤之一,严重威胁老年男性的生命健康。目前,前列腺癌根治术(Radical prostatectomy,RP)仍为局部前列腺癌的主要治疗手段。因受手术创伤及围手术期等因素影响,术后往往会出现明显的性功能障碍,主要表现为患者勃起功能障碍(Erectile dysfunction,ED),导致患者生活质量下降。近年来,机器人辅助腹腔镜前列腺癌根治术(Robot-assisted laparoscopic radical prostatectomy,RALP)在前列腺癌根治方面成效显著,不但降低了患者术后肿瘤复发率且术后性功能恢复明显。本文就机器人辅助腹腔镜前列腺癌根治术后性功能恢复做一综述,为前列腺癌患者术后性功能的恢复带来新的诊疗思路。     

Prostatakarzinom und erektile Dysfunktion

The quality of life of patients after radical prostatectomy is mainly influenced by erectile dysfunction (ED) and incontinence. New criteria for treatment and patient selection give us the opportunity to restore sexual function in more patients.When ED is present, we should not wait for 24 months for natural restitution. PDE-5-inhibitors, intracavernosal self injection therapy and the vacuum constriction device are effective and conform to both patient and economic preference.Therefore, every urologists should be able to offer his patients an individual and successful approach to the therapy of ED after prostate cancer.     

Penile rehabilitation after prostate cancer treatment: outcomes and practical algorithm

The number of patients diagnosed with prostate cancer was estimated to be 192,000 in 2009 according to the American Cancer Society. The prevalence of reported erectile dysfunction after radical prostatectomy has significant variance. Among the studies in which the nerve-sparing status was described, erectile function recovery adequate for sexual intercourse was achieved in 50% of patients. This article reviews the animal and human studies in this field and provides a useful penile rehabilitation algorithm.     

Penile rehabilitation after radical prostatectomy: does it work?

Context

Erectile dysfunction (ED) represents one of the most common long-term side effects in patients with clinically localized prostate cancer (PCa) undergoing nerve-sparing radical prostatectomy (RP).

Objective

To analyze the role of penile rehabilitation in the recovery of erectile function (EF) after nerve-sparing RP.

Evidence synthesis

Penile rehabilitation is defined as the use of any intervention or combination with the goal not only to achieve erections sufficient for satisfactory sexual intercourses, but also to return EF to preoperative levels. The concept of rehabilitation is based on the implementation of protocols aimed at improving oxygenation, preserving endothelial structure, and preventing smooth muscle structural alterations. Nowadays, the most commonly adopted approaches for penile rehabilitation after nerve-sparing RP are represented by the administration of phosphodiesterase type-5 inhibitors (PDE5-Is), intracorporeal injection therapy, vacuum erection devices (VED), and the combination of these therapies. Several basic science studies support the rational for the adoption of penile rehabilitation protocols. Particularly, rehabilitation, set as early as possible, seems to be better than leaving the erectile tissues unassisted. On the other hand, results from solid prospective randomized trials finally assessing the long-term beneficial effects of PDE5-Is, intracavernosal injections, or VED on EF recovery after surgery are still lacking.

Conclusions

Although preclinical evidences support the rationale for penile rehabilitation after nerve-sparing RP, clinical studies reported conflicting results regarding its efficacy on long-term EF recovery. Nowadays, which is the optimal rehabilitation program still represents a matter of debate.     

Prediction of postoperative sexual function after nerve sparing radical retropubic prostatectomy

PURPOSE: Preservation of sexual function is one of the main objectives in radical prostatectomy. We assessed possible predictive factors for postoperative sexual function including preoperative International Index of Erectile Function score, age and extent of nerve sparing procedures for more precise preoperative counseling of patients undergoing radical prostatectomy. MATERIALS AND METHODS: Between January 2000 and December 2001 a total of 694 patients with clinically organ confined prostate cancer underwent nerve sparing radical prostatectomy. Preoperative erectile function was assessed with the International Index of Erectile Function score. After at least 12 months of followup patients were asked to answer the International Index of Erectile Function and Quality of Life Questionnaire C 30 via mail. RESULTS: A total of 411 patients responded to the questionnaire, 122 of whom underwent unilateral nerve sparing radical prostatectomy and 289 underwent bilateral nerve sparing radical prostatectomy. Data on preoperative and postoperative International Index of Erectile Function scores were available for 389 patients. Data on the International Index of Erectile Function and the postoperative Quality of Life Questionnaire C 30 were available for 382 patients. The median decrease in International Index of Erectile Function score was 7 points. Patients undergoing unilateral nerve sparing radical prostatectomy had a significantly stronger decrease in International Index of Erectile Function score compared to patients undergoing the bilateral nerve sparing procedure (12 vs 6 points). Preoperative International Index of Erectile Function score and extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) were significantly associated with better postoperative sexual function whereas age was not. Based on preoperative International Index of Erectile Function score, surgical technique and age, the likelihood of postoperative satisfactory erectile function can be defined preoperatively. CONCLUSIONS: We confirmed the impact of the extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) and highlighted the effect of preoperative erectile function as measured by the International Index of Erectile Function and age at surgery on postoperative sexual function. Our data can be used for counseling patients undergoing radical nerve sparing prostatectomy regarding recovery of erectile function.     

Effect of radical retropubic prostatectomy on erectile function, evaluated before and after surgery using colour Doppler ultrasonography and nocturnal penile tumescence monitoring

OBJECTIVE: To assess the effect of radical retropubic prostatectomy on erectile function, by evaluating objectively patients' erectile function before and after surgery. PATIENTS AND METHODS: The study comprised 126 patients with clinically localized prostate cancer who were scheduled to undergo radical retropubic prostatectomy. After giving informed consent for the study, 123 patients underwent intracavernosal injection tests, colour Doppler ultrasonography and nocturnal penile tumescence monitoring before and after surgery. RESULTS: From the intracavernosal injection tests and nocturnal penile tumescence monitoring, 21 patients (17%) were evaluated as having normal erectile function before surgery. After radical retropubic prostatectomy, nine (43%) of these 21 potent men had preserved erectile function. In eight patients whose neurovascular bundles were preserved, five were potent after surgery. The cause of erectile function after surgery was a neurogenic disorder in seven and a related vascular disorder in five. CONCLUSION: From objective tests of erectile function on patients scheduled to undergo radical prostatectomy, 17% had normal erectile function. However, even after nerve-sparing radical retropubic prostatectomy, the proportion retaining potency was unsatisfactory. Although a neurological disorder was the main cause of erectile dysfunction after surgery, vascular disorders were also important.     

Current rehabilitation strategy: clinical evidence for erection recovery after radical prostatectomy

Erectile function (EF) recovery remains a prominent functional outcome underachievement of radical prostatectomy (RP), despite the success of anatomic “nerve-sparing” technique and its recent refinements in the modern surgical era. Delayed (for as much as a few years) or incomplete (partial and unusable) EF recovery commonly occurs in many men still today undergoing this surgery. “Penile rehabilitation”, alternatively termed “EF rehabilitation”, originated formally as a therapeutic practice approximately 15 years ago for addressing post-RP erectile dysfunction (ED) beyond conventional ED management. Although the premise of this therapy is conceptually sound and generally accepted, in reference to the implementation of strategies for promoting EF recovery to a naturally functional level in the absence of erectile aids (distinct from the premise of conventional ED management), the optimal manner and efficacy of currently suggested therapeutic strategies are far less established. Such strategies include regimens of standard ED-specific therapies (e.g., oral, intracavernosal, and intraurethral pharmacotherapies; vacuum erection device therapy) and courses of innovative interventions (e.g., statins, erythropoietin, angiotensin receptor blockers). An endeavor in evolution, erection rehabilitation may ideally comprise an integrative program of sexual health management incorporating counseling, coaching, guidance toward general health optimization and application of demonstrably effective “rehabilitative” interventions. Ongoing intensive discovery and rigorous investigation are required to establish efficacy of therapeutic prospects that fulfill the intent of post-RP erection rehabilitation.     

Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing radical prostatectomy

PURPOSE: The exact process and time required for rehabilitation of erectile function after nerve sparing prostatectomy remain unclear to date. Different theories of the pathophysiology of postoperative erectile dysfunction are currently being discussed. In a prospective study we performed recordings of nocturnal penile tumescence and rigidity during the acute phase after nerve sparing radical prostatectomy, ie in the first night after removal of the catheter, to assess the organic penile integrity. MATERIALS AND METHODS: In 27 patients with local prostate carcinoma who had been sexually active before the intervention, we performed unilateral or bilateral nerve sparing radical prostatectomy. Preoperative sexual function of all patients was evaluated by the International Index of Erectile Function-5 questionnaire. On the day of catheter removal (postoperative day 7 to 14) an NPTR recording was performed on the following night with an erectometer (RigiScan). RESULTS: All patients had a preoperative IIEF score greater than 18. After removal of the catheter 25 of 27 patients (93%) showed 1 to 5 nocturnal rigidity increases by greater than 70% for at least 10 minutes. In a control group of 4 patients who underwent radical prostatectomy without nerve sparing, no nocturnal erections were recorded. CONCLUSIONS: NPTR recording during the acute phase after nerve sparing radical prostatectomy showed residual erectile function as early as the first night after catheter removal. These results are significant for selecting adequate pharmacological treatment for optimal therapy and rehabilitation of satisfactory erections and sexual function. In cases of early nocturnal tumescence, application of a PDE5 inhibitor can support successive organ rehabilitation. However, if tumescence does not occur, penile injection therapy is recommended.     

Erectile dysfunction following treatment of prostate cancer: new insights and therapeutic options

Prostate cancer remains the most common cancer in adult men. Its treatment usually results in compromised or absent erectile function. This article will review the treatment options available to resume sexual activity following prostate cancer therapy and will focus on non-surgical treatment options. In addition, intracavernosal injection therapy has been shown to enhance recovery of spontaneous, unassisted erections when started shortly after nerve-sparing radical prostatectomy. Most recently, oral treatment with sildenafil citrate begun shortly after surgery was shown in a placebo-controlled trial to encourage return of normal erections. Presumably this occurs by promoting nocturnal erections which appear to prevent the permanent neurovascular damage to the penis following radical prostate surgery.     

Recovery of sexual function after nerve-sparing radical prostatectomy or cystectomy

BACKGROUND: The recovery of sexual function (erectile function and frequency of sexual intercourse) over time after nerve-sparing radical prostatectomy or cystoprostatectomy was evaluated. METHODS: Forty-nine consecutive patients with clinically localized prostate cancer and muscle-invasive bladder cancer were treated with radical prostatectomy and radical cystoprostatectomy with a nerve-sparing procedure. Erectile function was evaluated by the circumferential change of the penis during nocturnal penile tumescence (NPT value) with an erectometer before and after surgery. Erectile function and the frequency of sexual intercourse were also evaluated with a self-administered questionnaire before and after surgery. Multivariate analysis by Cox's proportional hazards model was used to evaluate the factor(s) that affected the recovery of erectile function and sexual intercourse. RESULTS: The recovery rates of erectile function were 49% at 3 years and 79% at 5 years. For recovery of sexual intercourse the rates were 36% at 3 years and 57% at 5 years. Multivariate analysis revealed that the preoperative NPT value was the only independent factor which significantly affected the recovery of erectile function. The age at surgery was a significant factor for recovery of sexual intercourse. CONCLUSION: Nerve-sparing operations can often, but not always, provide preservation or recovery of erectile function for patients who receive radical prostatectomy or cystoprostatectomy. Recovery of erectile function depends upon the preoperative NPT value and recovery of sexual intercourse depends upon the age of the patient.     

Penile rehabilitation following prostate cancer treatment: review of current literature

Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation.     

Salvage radical prostatectomy: quality of life outcomes and long-term oncological control of radiorecurrent prostate cancer

PURPOSE: We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer. Using a standardized questionnaire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy. MATERIALS AND METHODS: Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy. Clinical information was obtained from a prospective database. Quality of life data were collected using the UCLA Prostate Cancer Index, a validated, patient administered instrument. RESULTS: At 5 years 47% of patients were progression-free without androgen deprivation therapy. Among patients with pT2 disease 100% were progression-free at 5 years, compared with 35% of patients with pT3N0 disease or higher and 0% of patients with node positive (pTxN+) disease (p < 0.001). Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease, and strongly associated with prolonged progression-free and overall survival (p < 0.001 and 0.01, respectively). Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after standard, nonsalvage prostatectomy. Sexual dysfunction was nearly uniform in patients undergoing standard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinically significant improvement in sexual function. CONCLUSIONS: When initiated early in the course of recurrent disease, salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for androgen ablation. Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters.     

Effect of statin therapy on early return of potency after nerve sparing radical retropubic prostatectomy

PURPOSE: We prospectively investigated whether postoperative statin use would contribute to earlier recovery of erectile function in men who underwent bilateral nerve sparing radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 50 potent men without hypercholesterolemia undergoing bilateral nerve sparing radical retropubic prostatectomy for clinically localized prostate cancer were prospectively randomized into 2 equal groups. Group 1 patients were instructed to ingest only 50 mg sildenafil per day if needed following hospital discharge after radical retropubic prostatectomy. Group 2 patients were prescribed atorvastatin at a dose of 10 mg daily from postoperative days 1 to 90 and they were also instructed to ingest sildenafil, as in group 1. Patient status regarding potency and adverse events were assessed 6 months after surgery. RESULTS: The 2 groups demonstrated no significant differences regarding various baseline factors, including International Index of Erectile Function-5 scores. Group 2 had a significantly higher postoperative International Index of Erectile Function-5 score than group 1 at 6 months postoperatively (p = 0.003). Meanwhile, as judged by a preset definition, the incidence of potent patients 6 months after prostatectomy was 26.1% in group 1 and 55% in group 2 (p = 0.068). Also, 17.4% and 40% of the men reported achieving intercourse by vaginal penetration without a phosphodiesterase 5 inhibitor in groups 1 and 2, respectively (p = 0.172). No serious adverse events associated with medication were reported. CONCLUSIONS: Postoperative treatment with atorvastatin in men who report normal erectile function preoperatively may contribute to earlier recovery of erectile function after nerve sparing radical retropubic prostatectomy.     

Contexte et objectifs de l'étude repair

Radical prostatectomy is a curative option for the treatment of clinically localized prostate cancer. The neurovascular bundles preservation technique increases the chance of sexual activity recovery following surgery. Nevertheless, erectile dysfunction after radical prostatectomy has been reported to occur in up to 80% of patients. Urinary dysfunction is the other main complication of radical prostatectomy. In the literature, conflicting results have been reported regarding the incidence of sexual and urinary disorders following radical prostatectomy. In addition, data regarding urologists' habits for the care of patients following this surgery are sparse. In Repair study, extensive data were collected from both urologists and their patients to analyze the incidence, the consequences, and the way to take care of sexual and urinary disorders following radical prostatectomy.     

Growth factor therapy and neuronal nitric oxide synthase

Trauma to the cavernous nerve is a known cause of erectile dysfunction, with lengthy and often incomplete recovery. Using rat models, we have previously shown that injury to the cavernous nerves or ligation of pudendal arteries causes a significant decrease of neuronal nitric oxide synthase (nNOS) in the dorsal nerve of the penis and intracavernosal tissue as well as loss of erectile response to neurostimulation. Intracavernous injection of vascular endothelial growth factor or brain-derived neurotrophic factor facilitates the recovery of nNOS and erectile function. Studies are underway to elucidate the molecular mechanism of cavernous nerve regeneration and the potential of using growth factors to enhance the recovery of erectile function in patients after radical pelvic surgery. International Journal of Impotence Research (2004) 16, S38-S39. doi:10.1038/sj.ijir.3901214     

Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy

INTRODUCTION AND OBJECTIVES: As radical prostatectomy remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed current and future strategies for preventing and managing postoperative erectile dysfunction. METHODS: Systematic literature review using Medline and CancerLit from January 1997 to June 2003. Abstracts published in the journals European Urology, The Journal of Urology and the International Journal of Impotence Research as official proceedings of internationally known scientific societies held in the same time period were also assessed. RESULTS: Patient selection and surgical technique are the major determinants of postoperative erectile function. Apoptosis of corporeal smooth muscle cells plays a role in the development of cavernous veno-occlusive dysfunction following radical prostatectomy. Pharmacological prophylaxis and treatment of postoperative erectile dysfunction is effective and safe. The concepts of cavernous nerve reconstruction and neuroprotection have been associated to promising results. CONCLUSIONS: In the hands of experienced surgeons, properly selected patients undergoing a nerve sparing radical prostatectomy should achieve unassisted or medically assisted erections postoperatively.     

Bilateral nerve grafting during radical retropubic prostatectomy: extended follow-up

Objectives. To confirm the benefit of using an interposition sural nerve graft at the time of radical retropubic prostatectomy in an extended series of men with at least 1 year of follow-up. We previously reported the return of erectile function after resection of both cavernous nerves.Methods. Twenty-eight potent men with clinically localized prostate cancer underwent radical retropubic prostatectomy with deliberate wide bilateral neurovascular bundle resection and the placement of bilateral nerve grafts. Erectile dysfunction questionnaires and patient interviews were completed at 6-month intervals. A minimum of 12 months of follow-up (mean 23 ± 10 months) was obtained for 23 men (mean age 58 ± 6 years). A control group of 12 men who underwent bilateral nerve resections, but declined nerve graft placement, was also followed up.Results. Of the 23 men, 6 (26%) had spontaneous, medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 6 men (26%) described “40% to 60%” spontaneous erections (fullness, no rigidity, not able to penetrate). Ten men (43%) had intercourse with sildenafil. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function thus far was observed at 18 months after surgery.Conclusions. This surgical technique continues to show promise as an advance in prostate cancer surgery. The results of this study demonstrated recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.     

Does the CaverMap device help preserve potency?

Erectile dysfunction remains a common complication following radical prostatectomy. The CaverMap Surgical Aid (UroMed, Boston, MA) was designed to aid the surgeon in identifying and preserving neurovascular bundles (NVBs). However, the size of the CaverMap nerve stimulator may make it difficult to trace the cavernous nerves before the prostate is removed, particularly in obese men or in patients who have a large prostate or a narrow pelvis. In a randomized, controlled study, the use of the CaverMap during radical prostatectomy resulted in improved nocturnal erections, but did not lead to improved overall sexual function. The CaverMap device, however, may be useful as a research tool in that it helps determine whether the NVBs have been successfully preserved after removing the prostate. However, pre-servation of the NVB does not guarantee recovery of potency, which may be prolonged despite successful stimulation of the cavernous nerves intraoperatively. This suggests that erectile dysfunction following radical prostatectomy is multifactorial.