CAM 70181

Nerve Graft with Radical Prostatectomy

Category:Surgery   Last Reviewed:June 2018
Department(s):Medical Affairs   Next Review:June 2019
Original Date:November 2001    

Description:
Nerve grafting at the time of radical prostatectomy, most commonly using the sural nerve, has been proposed to reduce the risk of postoperative erectile dysfunction.

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. 

Background 
ERECTILE DYSFUNCTION
Erectile dysfunction is a common problem after radical prostatectomy. In particular, spontaneous erections are usually absent in men whose prostate cancer required bilateral resection of the neurovascular bundles as part of the radical prostatectomy procedure.

Treatment
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 and unilateral nerve grafts, the latter involving resection of 1 neurovascular bundle. 

There has been interest in sural nerve grafting to replace cavernous nerves resection during prostatectomy. The sural nerve is considered expendable and has been extensively used 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 1 leg and then anastomosed to the divided ends of the cavernous nerve. Reports also indicate the use of other nerves (e.g., genitofemoral nerve) for grafting.   

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 FDA through the 510(k) process. FDA product code: JXI. An example of a human tissue nerve graft product, the Avance® nerve graft (AxoGen), is regulated by FDA under the 21 CFR Part 1271 regulations for Human Cellular and Tissue-based Products (HCT/P).

Policy:
Unilateral or bilateral nerve graft is considered INVESTIGATIONAL in patients who have had resection of one or both neurovascular bundles as part of a radical prostatectomy. 

Policy Guidelines
There are no specific CPT codes describing sural nerve grafting of the cavernous nerves. The CPT codes describing nerve grafts specifically identify the anatomic site and do not include the cavernous nerves. Therefore, CPT code 64999 (unlisted procedure, nervous system) may be used to describe the nerve harvest and grafting component of the procedure. Alternatively, a nonspecific CPT code for nerve repair — 64910 or 64911 — may be used.

Benefit Application:
BlueCard®/National Account Issues

Nerve grafting in association with radical prostatectomy is a specialized procedure that may require out-of-network referral.

In some cases, the nerve-harvesting procedure may be performed by a plastic surgeon or a neurosurgeon. In other cases, a urologist may perform both the nerve-harvesting, graft and radical prostatectomy.

Specific contractual exclusions regarding treatment of impotence may apply.

Rationale
This evidence review was created in November 2001 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through February 5, 2018.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function -- including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice. 

NERVE GRAFTING
One randomized controlled trial evaluating nerve grafting to reduce the risk of erectile dysfunction has been published; findings were reported by Davis et al (2009).1 The trial included men age 65 years or younger with normal self-reported baseline erectile function selected for a unilateral nerve sparing radical prostatectomy with preservation of 1 neurovascular bundle. All patients had unilateral neurovascular bundle removal, and patients were randomized to receive or not sural nerve grafting after removal. The primary outcome was potency 2 years postsurgery, defined as the ability to have intercourse with or without erectile dysfunction medication. All patients received the same early erectile dysfunction therapy, including medication and mechanical devices. The investigators sought to detect an absolute difference of 20% between groups (graft, 60% potency rate vs no graft, 40% potency rate). A sample of 200 men was originally planned to provide 80% power. However, after 107 men were randomized, a preplanned interim analysis of evaluable patients found similar potency rates between groups. The data-monitoring committee stopped the trial based on its estimate of less than a 5% chance that additional recruitment would result in a significant difference between groups. End point data were available for 66 patients. Potency was achieved in 32 (71%) of 45 sural nerve graft patients and 14 (67%) of 21 control patients (p=0.78). Trialists concluded that unilateral sural nerve graft did not result in an absolute improvement of 20% between groups, but that a smaller effect could not be ruled out. A limitation of the trial was that it was unblinded, which, because men knew the procedure they received, could have impacted self-report of potency.

The literature also includes 2 retrospective cohort studies and 3 case series.2-6 The cohort studies are described below.

The cohort study by Kung et al (2015) 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 between groups (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. 

The second cohort study, published by Namiki et al (2007), included 113 patients: 19 had unilateral nerve sparing plus sural nerve graft, 60 patients had unilateral nerve sparing with no grafting, and 34 patients had bilateral nerve sparing surgery.3 Function was assessed using validated questionnaires and, at 2 years, no difference in sexual function scores was found between the unilateral nerve graft and bilateral nerve sparing patients. At 3 years, similar percentages of patients in the unilateral nerve graft (25%) and bilateral nerve sparing (28%) groups considered their sexual function as fair or good. Urinary function returned to baseline continence in the unilateral nerve graft and bilateral nerve sparing groups at 6 months and in the unilateral nerve sparing group at 12 months. Baseline sexual function differed between groups, which could have biased study findings: the nerve grafted and bilateral nerve sparing patients reported higher baseline function than the unilateral nerve sparing group.  

SUMMARY OF EVIDENCE
For individuals who have radical prostatectomy with resection of neurovascular bundles who receive nerve grafting, the evidence includes a randomized controlled trial, cohort studies, and case series. Relevant outcomes are functional outcomes, quality of life, and treatment-related morbidity. The randomized controlled trial 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. 

CLINICAL INPUT FROM PHYSICIAN SPECIALTY SOCIETIES AND ACADEMIC MEDICAL CENTERS
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.

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. Input from the 4 centers agreed that this procedure is considered investigational.

PRACTICE GUIDELINES AND POSITION STATEMENTS
The National Comprehensive Cancer Network guidelines on the treatment of prostate cancer (v.2.2018) states: "Replacement of resected nerves with nerve grafts has not been shown to be beneficial" for recovery of erectile function after radical prostatectomy.7 

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS
Not applicable. 

ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently unpublished trials that might influence this review are listed in Table 1.   

Table 1. Summary of Key Trials

NCT No. Trial Name Planned Enrollment Completion Date
Ongoing
NCT01770340 Nerve Grafting With an Allograft During Radical Prostatectomy - Extended Follow-up in a Prospective Randomized Trial 60 Jan 2019

NCT: national clinical trial. 

References: 

  1. Davis JW, Chang DW, Chevray P, et al. 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. May 2009;55(5):1135-1143. PMID 18783876
  2. Kung TA, Waljee JF, Curtin CM, et al. Interpositional nerve grafting of the prostatic plexus after radical prostatectomy. Plast Reconstr Surg Glob Open. Jul 2015;3(7):e452. PMID 26301141
  3. Namiki S, Saito S, Nakagawa H, et al. Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study. J Urol. Jul 2007;178(1):212-216; discussion 216. PMID 17499797
  4. Rabbani F, Ramasamy R, Patel MI, et al. Predictors of recovery of erectile function after unilateral cavernous nerve graft reconstruction at radical retropubic prostatectomy. J Sex Med. Jan 2010;7(1 Pt 1):166-181. PMID 19686422
  5. Siddiqui KM, Billia M, Mazzola CR, et al. 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
  6. Souza Trindade JC, Viterbo F, Petean Trindade A, et al. 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. Jun 2017;119(6):948-954. PMID 28093890
  7. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2.2018. https://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed March 12, 2018. 

Coding Section

Codes Number Description
CPT 64999

Unlisted procedure, nervous system

  55840-55845

Radical retropubic prostatectomy, code range

ICD-9 Procedure    
ICD-9 Diagnosis 185

Malignant neoplasm of prostate

  607.84

Impotence of organic origin

  997.99

Complications affecting other specified body systems, not elsewhere classified, other (to be reported with 607.84 when the impotence is a result of a previous radical prostatectomy)

  V45.77 Other postprocedural states; acquired absence of genital organs
HCPCS    
ICD-10-CM (effective 10/01/15)  

Investigational for all relevant diagnoses 

  C61

Malignant neoplasm of prostate 

  N52.01-N52.9

Male erectile dysfunction code range (includes N52.31 Erectile dysfunction following radical prostatectomy) 

ICD-10-PCS (effective 10/01/15)  

ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure. 

  0VT00ZZ

Surgical, male reproductive system, resection, prostate, open 

Type of Service Surgery  
Place of Service Inpatient  

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

06/01/2018

Annual review, no change to policy intent. Updating background, rationale and references. 

06/01/2017 

Annual review, no change to policy intent. Updating background, description, rationale and references. Adding regulatory status. 

06/01/2016 

Annual review, no change to policy intent. Updating title, background, description, rationale and references. Adding regulatory status. 

06/17/2015 

Annual review, no change to policy intent. Updated rationale and references. Added guidelines and coding. 

06/02/2014

Annual review. Updated rationale and references. No change to policy intent.

 


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