BlueAdvantage Administrators of Arkansas
Coverage Policy#: 417
Category: Surgery
Initiated: January 2004
Last Review: October 23, 2023
Last Revision: October 23, 2023
BlueAdvantage National Accounts
Coverage Policy for Participants and Beneficiaries enrolled in Walmart Associates' Health and Welfare Medical Plan
(Developed by BlueAdvantage Administrators and Adopted by the Walmart Plan as Plan Coverage Criteria)

Nerve Graft with Radical Prostatectomy


Description:
Nerve grafting to replace cavernous nerves resected at the time of radical prostatectomy is proposed to reduce the risk of erectile dysfunction after this surgery. The sural nerve is most commonly used in grafting.
 
Erectile dysfunction is a common problem after radical prostatectomy. In particular, spontaneous erections are usually absent in patients whose extent of prostate cancer requires bilateral resection of the neurovascular bundles as part of the radical prostatectomy procedure. A variety of noninvasive treatments are available, including vacuum constriction devices and intracavernosal injection therapy. However, spontaneous erectile activity is preferred by patients. Studies have reported results from bilateral nerve grafts; there are also reports of unilateral grafts when only one neurovascular bundle has been resected.
 
There has been interest in sural nerve grafting to replace cavernous nerves resected at the time of prostatectomy. The sural nerve is considered expendable and has been used extensively in other nerve grafting procedures, such as brachial plexus and peripheral nerve injuries. As applied to prostatectomy, a portion of the sural nerve is harvested from one leg and then anastomosed to the divided ends of the cavernous nerve. Reports are also being published using other nerves, such as the genitofemoral nerve.

Policy/
Coverage:
Unilateral or bilateral nerve graft is considered investigational in patients who have undergone resection of one or both neurovascular bundles as part of a radical prostatectomy.
 
Investigational services are Plan exclusions.

Rationale:
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
Not applicable.
 
REGULATORY STATUS
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).
 

CPT/HCPCS:
64999Unlisted procedure, nervous system

ICD9:
185Malignant neoplasm of prostate
607.84Impotence of organic origin
997.99Other complications affecting other specified body systems, NEC
V45.77Acquired absence of organ, genital organs

ICD10:
C61Malignant neoplasm of prostate
N52.01Erectile dysfunction due to arterial insufficiency
N52.02Corporo venous occlusive erectile dysfunction
N52.03Comb artrl insuff & corporo venous occlusv erectile dysfnct
N52.1Erectile dysfunction due to diseases classified elsewhere
N52.2Drug induced erectile dysfunction
N52.31Erectile dysfunction following radical prostatectomy
N52.32Erectile dysfunction following radical cystectomy
N52.33Erectile dysfunction following urethral surgery
N52.34Erectile dysfunction following simple prostatectomy
N52.39Other and unspecified postprocedural erectile dysfunction
N52.8Other male erectile dysfunction
N52.9Male erectile dysfunction, unspecified

References: Davis JW, Chang DW, Chevray P et al.(2009) Randomized phase II trial evaluation of erectile function after attempted unilateral cavernous nerve-sparing retropubic radical prostatectomy with versus without unilateral sural nerve grafting for clinically localized prostate cancer. Eur Urol 2009; 55(5):1135-44.

Kung TA, Waljee JF, Curtin CM, et al.(2015) Interpositional nerve grafting of the prostatic plexus after radical prostatectomy. Plast Reconstr Surg Glob Open. Jul 2015;3(7):e452. PMID 26301141.

Namiki S, Saito S, Nakagawa H et al.(2007) Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study. J Urol 2007; 178(1):212-6

National Comprehensive Cancer Network (NCCN).(2023) NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer.Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.

National Comprehensive Cancer Network.(2018) Prostate Cancer. Clinical practice guidelines in oncology, v2.2018 http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Last accessed November 2013.

NCT01770340.(2013) Nerve Grafting With an Allograft During Radical Prostatectomy - Extended Follow-up in a Prospective Randomized Trial. Available online at: www.clinicaltrials.gov. Last accessed November, 2013.

Rabbani F, Ramasamy R, Patel MI et al.(2010) Predictors of recovery of erectile function after unilateral cavernous nerve graft reconstruction at radical retropubic prostatectomy. J Sex Med 2010; 7(1 pt 1):166-81.

Secin FP, Koppie TM, Scardino PT et al.(2007) Bilateral cavernous nerve interposition grafting during radical retropubic prostatectomy: Memorial Sloan-Kettering Cancer Center experience. J Urol 2007; 177(2):664-8.

Siddiqui KM, Billia M, Mazzola CR, et al.(2014) Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting. J Sex Med. Aug 2014;11(8):2119-2124. PMID 24903070.

Souza Trindade JC, Viterbo F, Petean Trindade A, et al.(2017) Long-term follow-up of treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorraphy: a new technique. BJU Int. Jan 17 2017. PMID 28093890.


The Walmart Plan is a self-funded health plan served by BlueAdvantage Administrators and has adopted all of the Coverage Policies listed here as benefit criteria applicable to its health plan.

CPT Codes Copyright © 2024 American Medical Association.
417 7.01.81 202310 10/31/2023