This evidence review has been updated regularly with literature searches of the MEDLINE database. Most recently, the literature was reviewed through January 16, 2023. Following is a summary of the key literature to date.
A single randomized controlled trial (RCT) that evaluated nerve grafting to reduce risk of erectile dysfunction was published in 2009 by Davis and colleagues. Eligibility criteria included age 65 or younger, normal self-report baseline erectile function, and scheduled for a unilateral nerve-sparing radical prostatectomy with preservation of one neurovascular bundle. All patients had the other neurovascular bundle removed, and patients were randomly assigned to receive or not receive sural nerve grafting after its removal. The primary outcome was potency 2 years post-surgery, defined as the ability to have intercourse with or without erectile dysfunction medication. The investigators estimated that the control group would have a 40% potency rate and powered the study to detect an absolute difference of 20% between groups. All patients received the same early erectile dysfunction therapy including medication and mechanical devices. A sample size of 200 was originally planned to provide 80% power. However, after 107 patients were randomly assigned, a pre-planned interim analysis of evaluable patients found similar rates of potency in the two groups; the Data Monitoring Committee estimated that there was less than a 5% chance that there would be a significant difference between groups with additional recruitment and the trial was stopped early. When data collection ended, endpoint data were available for 66 patients who had either achieved potency or had been followed up for 2 years without potency. Potency was achieved in 32 of 45 (71%) sural nerve graft patients and 14 of 21 (67%) control patients (p=0.78). The authors concluded that unilateral sural nerve graft did not result in an absolute improvement of 20% in the rate of potency but that a smaller effect cannot be ruled out. A limitation of the study was that it was non-blinded, which could have impacted self-report of potency.
The literature also includes 2 retrospective cohort studies and 3 case series (Kung et al, 2015; Namiki et al, 2007; Rabbani et al, 2010; Siddiqui et al, 2014; Sousa et al, 2017). The cohort studies are described below.
A 2015 cohort study by Kung et al included 38 patients who underwent nerve grafting after radical prostatectomy and a random sample of 53 control patients who had open prostatectomy without nerve grafting. Control patients had unilateral or bilateral nerve sparing prostatectomy, or non-nerve sparing prostatectomy. Complete urinary incontinence, no erectile capacity at baseline, and follow-up data less than 12 months were study exclusion criteria. Unilateral nerve grafting (n=29) and unilateral nerve sparing (n=10) patients did not differ significantly (p>0.05) on various outcomes, including urinary continence, erections sufficient for sex, spontaneous erections, and use of erectile dysfunction medications. Bilateral nerve grafting (n=9) and bilateral non-nerve sparing (n=10) patients had similar outcomes (p>0.05). This study lacked randomization and blinding, and subgroup analyses included small numbers of patients.
Other than the Davis et al study, the published literature consists of case series. The largest published series and those with the longest follow-up are described below:
In 2007, Namiki and colleagues published a series in Japan with 3-year follow-up. A total of 113 patients were evaluated: 19 patients with unilateral nerve sparing plus sural nerve graft, 60 patients with unilateral nerve sparing but no grafting, and 34 patients with bilateral nerve-sparing surgery. Sexual function was assessed with validated questionnaires, and at 2 years there was no difference between the nerve-grafted and the bilateral nerve-sparing patients with regard to sexual function scores. At 3 years, 25% and 28% of patients in the nerve- grafted and bilateral nerve-sparing groups, respectively, considered their sexual function as fair or good. Urinary function returned to baseline in the nerve-grafted and bilateral nerve-sparing groups at 6 months and in the unilateral nerve-sparing group at 12 months. Differences in sexual function were present at baseline with the nerve-grafted and bilateral nerve-sparing patients reporting higher baseline function than the unilateral nerve-sparing group.
A 2010 case series reviewed the records of 131 men who had unilateral nerve grafts after radical prostatectomy with unilateral neurovascular bundle resection (Rabbani, 2010). Men who had prior radiation or hormonal treatment were excluded. Another eligibility criterion was satisfactory erections presurgery as assessed by a 5-point scale (1=full erections; 2=diminished erections, but routinely sufficient for sexual intercourse; 3=partial erections occasionally satisfactory for intercourse; 4=partial erections unsatisfactory for intercourse; and 5=no erections). A total of 49 men received sural nerve grafts, 79 received genitofemoral nerve grafts, and 3 received ilioinguinal nerve grafts. Recovery of erections was evaluated at each follow-up visit according to the 5-point scale (also called 5 levels). The median patient age was 58.7 years, and the median follow-up was 37 months. According to actuarial analysis, the 5-year probability of recovering erections of level 3 or better was 46%. The probability of recovering erections of at least level 2 or level 1 was 34% and 12%, respectively.
In 2014, Siddiqui et al. reported 3-year follow-up on 66 men with clinically localized prostate cancer who had undergone sural nerve grafting during radical retropublic prostatectomy. Forty-three (65%) were unilateral nerve grafts, and 23 (36%) were bilateral. All procedures were performed by a single surgeon. Recovery of potency was defined as a postoperative International Inventory of Erectile Function (IIEF) core greater than 22. Patients were permitted to use phosphodiesterase type 5 inhibitors for erectile dysfunction. The mean preoperative IIEF score was 23.4 (SD=1.6), and postoperatively, 19 patients (28.8%) recovered potency i.e., had an IIEF score greater than 22. When stratified by graft type, erectile function recovery rates were 28% after unilateral and 30% after bilateral nerve grafting.
SUMMARY OF EVIDENCE
For individuals who have radical prostatectomy with resection of neurovascular bundles who receive nerve grafting, the evidence includes 1 randomized controlled trial (RCT), cohort studies, and case series. Relevant outcomes are functional outcomes, quality of life, and treatment-related morbidity. The RCT did not find that unilateral nerve grafting was associated with a statistically significant improvement in potency rates at 2 years postsurgery. Cohort studies also did not result in better outcomes with nerve grafting. The evidence is insufficient to determine the effects of the technology on health outcomes.
Ongoing and Unpublished Clinical Trials
Nerve Grafting With an Allograft During Radical Prostatectomy - Extended Follow-up in a Prospective Randomized Trial (NCT01770340): This single-blind study includes 60 patients with prostate cancer. Patients have been randomized to receive radical prostatectomy with or without implantation of an allogenic nerve graft. The primary outcome is erectile function and follow-up is at least 24 months post-surgery.
Clinical Input Received Through Physician Specialty Societies and Academic Medical Centers
In response to requests, input was received from 4 academic medical centers while this policy was under review in 2008; no input was received from physician specialty societies. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. Input from these 4 centers agreed that this procedure is considered investigational as adopted in the policy in May 2008.
PRACTICE GUIDELINES AND POSITION STATEMENTS
The National Comprehensive Cancer Network guidelines on the treatment of prostate cancer guideline (v.1.2023) states, “that “Replacement of resected nerves with nerve grafts has not been shown to be beneficial,” for recovery of erectile function after radical prostatectomy.
U.S. Preventive Services Task Force Recommendations
A nerve graft with radical prostatectomy is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration (FDA).
Several nerve cuff products have been cleared for marketing by the FDA through the 510(k) process. (FDA product code: JXI). An example of a human tissue nerve graft product, the Avance® nerve graft (AxoGen, Inc.), is regulated by the FDA under the 21 CFR Part 1271 regulations for Human Cellular and Tissue-based Products (HCT/P).