Nerve Repair for Erectile Dysfunction After Radical Prostatectomy: A Systematic Review of Outcomes

Abstract

Background:

Erectile dysfunction (ED) is a prevalent complication after radical prostatectomy (RP), affecting up to 89% of patients within 2–5 years due to cavernous nerve injury. Nerve grafting has been proposed as a strategy to restore erectile function, but outcomes remain inconsistent, and randomized controlled trials have yielded mixed results. This review evaluated the effectiveness of nerve grafting techniques for ED management after RP.

Methods:

A systematic search of PubMed, MEDLINE, and Embase databases was conducted using terms related to ED, nerve grafting, and cavernous nerve repair. From 239 initial studies, 17 met the inclusion criteria, focusing on human subjects and reporting outcomes of unilateral or bilateral nerve grafting with autologous donor nerves, such as the sural and genitofemoral nerves.

Results:

Bilateral sural nerve grafting demonstrated the highest recovery rates, with up to 71% of patients regaining erectile function sufficient for intercourse. Adjunctive therapies like sildenafil were frequently used to enhance outcomes. However, randomized controlled trials showed no statistically significant improvements compared with controls, raising questions about the efficacy of nerve grafting. Variability in outcomes seemed to be influenced by donor nerve choice, surgical expertise, and patient characteristics, such as age and baseline function.

Conclusions:

Although bilateral sural nerve grafting offers promising results, its overall efficacy is uncertain due to inconsistent findings and limitations of existing studies. Larger, standardized trials are essential to clarify its role in ED management after RP and to optimize patient outcomes.

Takeaways

Question: What is the efficacy of nerve grafting and transfer techniques for restoring erectile function in men after radical prostatectomy?

Findings: This systematic review analyzed 17 studies involving nerve grafting techniques, such as sural nerve and genitofemoral nerve grafts. Bilateral sural nerve grafting demonstrated the highest erectile function recovery rates (up to 71%), but randomized controlled trials showed mixed efficacy. Factors such as surgical expertise, patient characteristics, and adjunctive therapies (eg, sildenafil) significantly influenced outcomes.

Meaning: Bilateral sural nerve grafting offers a promising but inconsistent solution for erectile function recovery after prostatectomy, warranting further research through standardized trials.

INTRODUCTION

Sexual disorders in men are subcategorized into sexual dysfunction or erectile dysfunction (ED) and arousal dysfunction or reduced sexual sensation.¹ The consequences of sexual dysfunction are well established and include but are not limited to reduction in self-esteem, impaired psychological well-being, and relationship discord.² Approximately 288,300 men are diagnosed with prostate cancer each year in the United States.³ Current guidelines recommend radical prostatectomy (RP) as the treatment of choice, which may result in 59%–79% in ED at 2–5 years after operation.^4,5 ED is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. The predominant cause of ED after RP is injury to cavernous nerve (CN) bundles.⁶ The CNs are postganglionic parasympathetic fibers that play a major role in penile erection by transmitting signals to the corpus cavernosum and cause a release of nitric oxide that relaxes the smooth muscles around the vessels and causes blood engorgement.⁷

Although techniques such as nerve-sparing prostatectomies have reduced the risk of ED, almost 70% of patients who undergo RP experience persistent ED, and rates of ED approach to almost 100% in nonnerve-sparing procedures.⁸ This negative outcome motivated interest into surgical interventions such as nerve grafting and transfer to solve this challenging problem.

Nerve grafting involves using autologous donor nerves, such as the sural or genitofemoral nerves, to reconstruct the damaged CN pathways. This technique has demonstrated promising results, especially when done bilaterally, with erectile function recovery rates of up to 71% and improvements in sexual quality of life, although outcomes still remain inconsistent, with randomized controlled trials (RCTs) failing to demonstrate significant benefits compared with controls (Davis et al 2009).^9–11 By closely analyzing the variability in outcomes of these studies, this review aimed to identify whether nerve graft effectively restores erectile function after RP.

MATERIALS AND METHODS

An advanced search of published articles in English on PubMed and MEDLINE from 1990 to 2023 was performed by 3 reviewers independently using a comprehensive set of keywords and Medical Subject Headings terms to ensure thorough coverage. The search included terms related to ED such as “erectile dysfunction,” “sexual dysfunction,” “erectile function,” “impotence,” and “penile erection.” It also incorporated terms addressing surgical and nerve repair techniques, including “nerve graft,” “neurorrhaphy,” “nerve reconstruction,” “nerve regeneration,” “autologous nerve graft,” and “peripheral nerve repair.” Specific terms for CN injury and context were used, such as “cavernous nerve injury,” and “penile neurovascular bundle.” Studies were included if they involved human subjects, reported outcomes on nerve grafting for ED after RP, used autologous donor nerves, and provided measurable functional outcomes (Table 1). Studies were excluded if they focused solely on animal models, were review articles or editorials, or lacked specific outcome measures for erectile function recovery (Table 1). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart outlines the process of screening and selecting studies for the review (Fig. 1). Initially, 239 records were identified from 3 databases: Embase, MEDLINE, and PubMed (Fig. 1). After removing 22 duplicate records, 217 records were screened by title, of which 87 were excluded for irrelevance or explicit mention of nonhuman subjects such as “rats” or “rodents.” The remaining 130 records were screened by abstract, leading to the exclusion of 102 records because of wrong study design or mention of nonhuman subjects. From this, 28 records were assessed in full text, with 11 further excluded for irrelevance or incorrect study design. Finally, 17 studies were eligible and included in the final review. This process ensured that only relevant and high-quality studies were included in the analysis (Fig. 1).

Table 1.

Inclusion and Exclusion Criteria, and Search Strategy of PubMed, MEDLINE, and Embase Databases

Inclusion Criteria	Exclusion Criteria
English language	Non-English articles
Cohort studies, case–control studies, and RCTs	Case reports, reviews, commentaries, or expert opinions
Studies published between 1990 and 2023	Studies published before 1990
Research involving nerve grafting or nerve transfer techniques for ED	Studies focusing on ED unrelated to nerve injury (eg, vascular, psychogenic, or hormonal causes)
Studies assessing erectile function recovery after RP	Research involving animal models or in vitro studies
Human studies with reported surgical outcomes using validated tools (eg, IIEF scores, patient-reported outcomes)	Studies without clear outcome measures or insufficient methodological details
The search strategy incorporated the following MeSH terms and keywords: • Erectile dysfunction (MeSH) OR Erectile function recovery OR Sexual dysfunction OR Penile erection. • Nerve grafting (MeSH) OR Nerve reconstruction OR Cavernous nerve injury OR Neurorrhaphy OR Peripheral nerve repair. • Radical prostatectomy (MeSH) OR Prostate cancer surgery OR Cavernous nerve preservation. The terms related to ED were combined with surgical repair techniques to refine the search for studies specifically addressing nerve repair in erectile function recovery.

MeSH, Medical Subject Headings.

Fig. 1.

PRISMA flow chart. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

RESULTS

This review analyzed 17 studies from 1990 to 2023 to assess the effectiveness of nerve grafting techniques for managing ED after RP. (See table, Supplemental Digital Content 1, which displays the outcomes of nerve reconstruction techniques in erectile function recovery after RP, https://links.lww.com/PRSGO/E372.)

Bilateral Nerve Grafting Approaches

Cavallo and Tewari¹² conducted a study involving 10 patients with confirmed ED 24 months after RP. The surgical procedure involved bilateral sural nerve grafts connecting the femoral nerve to the corpus cavernosum via the CNs for erectile function and to the dorsal nerve of the penis for penile sensation. All patients had flaccid erections within 6 months after the surgery, with 80% achieving semirigid or rigid erections at 12 months and 60% achieving penetration by 18 months.¹²

Kim et al¹³ documented outcomes in 9 patients who underwent RP with bilateral sural nerve grafting. One patient achieved spontaneous erections sufficient for intercourse at 14 months, demonstrating feasibility but limited early efficacy.¹⁴ Kim et al⁹ reported on 28 patients undergoing bilateral nerve resection with sural nerve grafting. At 1 year, 26% achieved spontaneous erections sufficient for intercourse and 43% used sildenafil to achieve intercourse, significantly outperforming controls.⁹ Kim et al,¹⁵ in a separate cohort study, followed 12 men undergoing bilateral nerve resection with sural nerve grafting. At 1 year, 33% achieved spontaneous erections sufficient for intercourse and 75% regained some erectile activity, significantly outperforming controls.¹⁵

Secin et al¹⁶ conducted a retrospective cohort study on 44 patients who underwent bilateral CN resection and autologous nerve grafting using sural, genitofemoral, or ilioinguinal nerves. Within 5 years, 34% of patients achieved erections sufficient for intercourse, although consistent results were limited to 11%.¹⁶

Unilateral Nerve Grafting Approaches

Fujioka et al¹⁷ analyzed outcomes for 8 patients with prostate cancer requiring unilateral CN resection. A sural nerve threaded through an autologous saphenous vein was used as a nerve graft. Spontaneous erectile activity returned in 7 patients, and 6 achieved intercourse, with an average recovery time of 8.75 months.

Joffe and Klotz¹⁸ studied 22 patients who underwent unilateral nerve-sparing RP combined with contralateral genitofemoral nerve grafting to reconnect the resected CN. Only 32% of patients achieved unassisted erections suitable for intercourse, with no notable benefit compared with standard nerve preservation.¹⁸

Namiki et al⁸ followed 113 patients who were divided into 3 groups: unilateral sural nerve graft, bilateral nerve sparing (BNS), and unilateral nerve sparing without grafting (UNS). The unilateral sural nerve graft group demonstrated significant recovery of sexual and urinary functions, achieving outcomes close to BNS.⁸

Saito et al¹⁹ examined 64 patients undergoing RP, dividing them into groups receiving unilateral nerve grafting, bilateral nerve sparing, and unilateral nerve sparing without grafting (UNS). The UNG group demonstrated superior sexual function recovery compared with the UNS group and achieved parity with BNS outcomes by 18 months.¹⁹

Porpiglia et al²⁰ compared outcomes in 29 men undergoing laparoscopic RP with unilateral sural nerve grafting versus unilateral nerve sparing alone. In the nerve graft group, 5 of 12 men achieved spontaneous or sildenafil-assisted erections, compared with 3 of 10 in the nerve-sparing group.²⁰

Anastasiadis et al¹⁴ examined 12 patients undergoing RP or cystoprostatectomy, all receiving unilateral sural nerve grafting. Four patients regained spontaneous erections sufficient for intercourse, with recovery timelines ranging from 3 to 24 months.

Comparative Studies on Nerve Grafting Outcomes

Davis et al¹⁰ evaluated 107 patients in an RCT to compare unilateral nerve-sparing RP with or without sural nerve grafting. The results showed no statistically significant differences in potency recovery, time to recovery, or International Index of Erectile Function (IIEF)-6 scores at 2 years after the surgery.¹⁰

Zorn et al¹¹ investigated 111 patients younger than 65 years of age with localized prostate cancer and normal preoperative erectile function. Unilateral sural nerve grafting performed alongside RP resulted in potency rates of 44% in the graft group and 43% in controls, with no significant improvement observed.¹¹

Sugimoto et al²¹ evaluated 88 patients, 24 of whom underwent CN reconstruction with sural nerve grafting, whereas the remaining received no nerve-sparing procedures. Erectile function recovery was 66.7% in the graft group, compared with 6.3% in controls, although dissatisfaction with outcomes was high.²¹

Alternative Nerve Grafting Techniques

Satkunasivam et al²² performed a retrospective cohort study on 33 patients who underwent unilateral or bilateral CN interposition grafting with autologous nerves, such as the genitofemoral or sural nerves. Bilateral nerve-sparing techniques resulted in potency rates of 50%–80%, whereas unilateral nerve sparing achieved roughly half these rates.²²

Reece et al⁶ conducted a retrospective case series of 17 men with ED after RP. Bilateral end-to-side sural nerve grafts were performed, leading to 71% regaining erectile function sufficient for intercourse and 94% reporting significant improvements in sexual quality of life.⁶

Nerve Transfer Techniques

Souza Trindade et al²³ studied 10 patients who had undergone RP at least 2 years earlier. The surgical technique used bilateral sural nerve grafts with end-to-side neurorrhaphies connecting the femoral nerve to the corpus cavernosum and the dorsal penile nerve. Sixty percent of patients achieved full penetration within an average of 13.7 months, whereas 40% attained partial erections. IIEF scores showed significant improvement at 12 and 18 months.²³

DISCUSSION

Nerve grafts and nerve crossovers as a management for ED are promising solutions and potentially life changing for men with nerve damage. We performed a literature search and found 17 studies on humans addressing the concept of nerve grafts in the context of ED.

The pathophysiology of ED after RP is primarily neurogenic and mainly related to CN injury.¹³ Although nerve-sparing prostatectomy is now an option, the bilateral or unilateral CN sometimes has to be resected to avoid positive margins and maximize cancer control.^6,24 However, regardless of the surgical technique, about 70% of men will still be burdened with ED after RP, whereas nonnerve-sparing post-RP ED rates approach 100%.

Among the 17 studies, there was a variability in the efficacy of nerve grafting for restoring erectile function after RP. (See table, Supplemental Digital Content 1, https://links.lww.com/PRSGO/E372.) Eight of these studies focused specifically on UNG: 6 used bilateral grafting, and 3 used both unilateral and bilateral approaches. For patients with partial nerve resection, unilateral grafting was the treatment of choice, but outcomes were mixed. Compared with UNG in patients with bilateral nerve resection, patients undergoing bilateral nerve grafting consistently showed better outcomes. For example, Yan et al (2019) reported a 71% recovery rate of erectile function sufficient for intercourse after bilateral end-to-side sural nerve grafting, with an impressive 94% of patients experiencing improvements in sexual quality of life. Similarly, Kim et al¹⁵ found that bilateral sural nerve grafting achieved spontaneous erections in 33% of patients and some erectile activity in 75%, outperforming controls that did not undergo nerve grafting. These findings suggest that, when compared with unilateral graft or no graft at all, bilateral approaches offer a better recovery rate. In another study conducted by Joffe and Klotz,¹⁸ UNG produced less consistent results with only 32% of patients achieving unassisted erections, showing no significant improvement over unilateral nerve-sparing procedures. Furthermore, studies that combined both unilateral and bilateral techniques showed a clear distinction in recovery rates between both techniques. Bilateral grafting achieved potency rates ranging from 50% to 80%, whereas unilateral grafting typically produced lower recovery rates.^8,22 In a retrospective series of 33 patients, unilateral grafting yielded a 31% potency rate, compared with 38% for bilateral grafting.¹⁰ Another report found 47.8% potency after unilateral sural grafting versus 56% in age-matched unilateral nerve-sparing controls (mean follow-up 26 mo).¹⁰ No randomized comparisons exist between unilateral and bilateral grafting. Cohort studies suggest some advantage for bilateral grafting, but these differences were not statistically significant and may be confounded by patient selection.¹⁰

The choice of donor nerve used in the graft varied among different studies and seemed to have an influence on the outcome. Studies using sural nerve grafting seemed to have more successful outcomes in terms of erectile function. Thirteen of the analyzed studies used sural nerve grafts either alone or in combination with other techniques, emphasizing its feasibility.

Namiki et al⁸ in a prospective cohort study including 113 patients concluded that unilateral sural nerve grafting significantly improved sexual and urinary functions. These outcomes were comparable to studies with bilateral nerve-sparing prostatectomies. Similarly, the study by Saito et al¹⁹ that involved 64 patients found that sural nerve grafting led to sexual function recovery that matched BNS by 18 months after the surgery. On the other hand, studies such as the case series by Joffe and Klotz¹⁸ using genitofemoral nerve grafting in 22 patients concluded that the graft did not provide significant benefits for erectile function recovery compared with unilateral nerve preservation alone. These variations could be explained by surgeons being more familiar with sural nerve dissection and extraction, and feasibility and size match of the sural nerve to the cavernous plexus nerves. Fewer studies compare nerve transfer techniques, such as genitofemoral interposition, to traditional sural or cavernous grafting. According to Nelson et al,²⁵ 56% potency (mean follow-up 14 mo) was seen in a cohort receiving genitofemoral nerve grafts, aligning with 50%–60% rates seen in a sural graft series.²⁵ However, no direct randomized comparisons exist, and these findings come from small, noncomparative cohorts, limiting definitive conclusions.

Several studies have identified key predictors for erectile function after CN grafting. Age at surgery has been consistently associated with outcomes; in a combined unilateral and bilateral graft cohort, older age significantly predicted poorer potency (P = 0.02).^10,16,26 Preoperative erectile function and the extent of neurovascular bundle preservation are likewise strong predictors. A multivariate analysis by Rabbani et al²⁶ specifically underscored patient age, preoperative IIEF score, and nerve-sparing status as independent predictors of postoperative potency.²⁶

It is also important to note that adjunctive therapies such as the use of sildenafil played an important role in further enhancing erectile function. Studies by Fujioka et al¹⁷ and Kim et al⁹ highlighted that many patients achieving intercourse after grafting relied on sildenafil support.

Sildenafil, a phosphodiesterase type 5 inhibitor, has demonstrated neuroprotective effects that may enhance nerve grafting outcomes after CN injury. According to Garcia et al,²⁷ sildenafil reduces oxidative stress and inflammation in the pelvic ganglia neurons after bilateral CN damage. By inhibiting reactive oxygen species production, sildenafil helps to prevent neuronal apoptosis, thereby supporting long-term nerve survival and regeneration. Similarly, Hlaing et al²⁸ demonstrated that sildenafil promotes neuroprotection of the pelvic ganglia neurons after bilateral cavernosal nerve resection in a rat model. The study found that sildenafil enhances nitric oxide signaling, which improves nerve perfusion and function, facilitating a more effective nerve regeneration process. These findings suggest that sildenafil, beyond its known vasodilatory effects, plays a crucial role in maintaining nerve health, preserving neuronal integrity, and promoting functional nerve recovery after injury or grafting. This shows that although nerve grafting is essential to restore neural pathways, pharmacological support is often as important to achieve satisfactory outcomes and might be crucial to optimize recovery.

RCTs reported mixed outcomes regarding the efficacy of the nerve graft and were not as promising as outcomes seen in observational studies. The RCT conducted by Davis et al¹⁰ and Zorn et al¹¹ that involved 107 patients and 111 patients, respectively, found no statistically significant differences in potency recovery between patients who underwent nerve grafting and those who did not. The lack of significant difference raises some questions about the real efficacy of nerve grafting procedures and shows that the positive results seen in smaller case series may be influenced by patient selection, surgical expertise, or other confounding factors. To validate the benefits of nerve grafting, further research will be needed as studies with higher statistical superiority lack significant results when using nerve grafting for ED. Predictors of successful erectile recovery after nerve grafting include younger patient age, superior baseline erectile function (eg, higher IIEF), bilateral grafting versus unilateral, and adherence to early rehabilitation protocols. Rabbani et al²⁶ identified patient age, preoperative IIEF score, and nerve-sparing status as independent predictors. Davis et al¹⁰ confirmed age as a strong predictor within a bilateral graft group (P = 0.02), whereas rehabilitation compliance modulated overall potency rates.²⁶

Other factors that might be influencing outcomes may be patient selection and expectations, as this will affect reporting patient satisfaction. Several studies emphasized the importance of considering patient characteristics such as age, baseline erectile function, and comorbidities. For example, Sugimoto et al²¹ highlighted that although nerve-grafted patients achieved higher recovery rates, dissatisfaction with sexual outcomes persisted due to a disconnection between functional recovery and patient expectations. These findings highlight the necessity of individualized patient counseling to set realistic expectations regarding recovery timelines and outcomes.

The studies reviewed have some clear limitations. Many studies had small sample sizes, making it hard to draw strong and significant conclusions. Most were case series or observational studies, which are less reliable than RCTs. There were only a few studies, such as Davis et al¹⁰ and Zorn et al,¹¹ that used RCTs, and even these did not show significant benefits. Measures of success varied across different studies as some focused on outcomes like erectile function scores and others on recovery timelines, making comparisons difficult. Moreover, patient satisfaction was not always fully addressed, showing that recovery is not just about function but also how patients feel. Larger, standardized studies are needed for clearer and more reliable results. Penile sensory outcomes after CN grafting are underreported. Available case series and clinician assessments indicate that grafting can maintain or restore penile sensitivity, although objective measurement data remain scarce. Future studies should include validated sensory outcome instruments. Recent translational works with bioengineered nerve conduits (eg, collagen tubes, autologous vein sheaths, and nerve growth factor vectors) demonstrate promising outcomes in preclinical models.^29,30 For instance, collagen tube grafts achieved functional recovery in animal studies and herpes simplex virus-mediated glial cell line–derived neurotrophic factor delivery improved erectile function after CN injury.^29,30 Although human data are preliminary, these innovations represent a promising future direction beyond autologous grafting.

CONCLUSIONS

Although bilateral sural nerve grafting shows promising results for erectile function recovery after RP, especially when combined with adjunctive therapies like sildenafil, its efficacy is still uncertain. The sural nerve’s structural compatibility might make it the preferred donor, as comparison of the studies showed it as outperforming alternatives like the genitofemoral nerve. However, due to limitations of small sample sizes, reliance on low level of evidence study designs, difference in measuring outcomes, and difference in outcomes themselves, further research is needed to establish a firm conclusion on the efficacy of nerve grafting. Finally, the RCTs failed to show significant improvements with nerve grafting compared with controls, highlighting the need for further studies.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.