Can nerve grafts restore erectile function?

Until 1981, urologists believed that the nerves responsible for erections ran through the prostate. But that year, Dutch urologist Pieter Donker showed that the nerves ran down the sides of the gland, not through it. That discovery got urologic surgeons thinking: perhaps a cancerous prostate could be removed without harming the nerves, preserving a man’s erectile function.

The following year, the first so-called nerve-sparing radical prostatectomy was performed. Today, most surgeons aim to spare the neurovascular bundles when performing prostate surgery. This helps men who were potent prior to surgery regain erectile function, and some studies show that it may also minimize urinary incontinence.

Unfortunately, the surgeon, whose main goal is to eliminate the cancer, can’t always spare the nerves. For example, the cancer might have grown through the prostate capsule and into the nerves, making their removal a must. Or the cancer might be at the edges of the gland, increasing the risk that a few cancerous cells might be left behind; the surgeon might make a wider cut to ensure a cure but sacrifice erectile nerves in the process. In some cases, neither nerve bundle can be saved.

Without at least one nerve bundle, the chances of recovering sufficient erectile function for sexual intercourse are quite slim. (Even if both nerve bundles are preserved, 30% or more of patients report erectile dysfunction. Those men who do have erections often complain about the quality of the erection.) And despite the fact that medications and devices, such as a vacuum pump, can help a man achieve an erection, men want their own spontaneous erections to return after a radical prostatectomy.

Figure 1: Sural nerve

Sural nerve

The sural nerve runs down the back of the ankle and along the side of the foot. Surgeons typically use this nerve to replace portions of the cavernous nerves that are removed during a radical prostatectomy. They can harvest the sural nerve through a small incision around the ankle bone. Some patients report tingling and numbness on the outside of the foot after the nerve has been removed (pink area above), sensations that seem to lessen over time.

Studies in rats proved that the cavernous nerves — the medical name for the nerve bundles that stretch from the prostate to the penis — could be replaced with nerve grafts, which could help restore erectile function in the animals. Once again, enterprising researchers and surgeons started thinking about the possibilities. A team in Texas devised a procedure during which about eight inches of the sural nerve would be removed from the foot (see Figure 1). Immediately following the prostatectomy, a nerve segment about three inches long would be inserted between the cut ends of each cavernous nerve and stitched into place (see Figure 2); the graft would provide a framework through which regenerating nerve cells could grow. With the plan firmly in place, the Texas surgeons operated on their first patient in 1997.

Figure 2: Inserting the graft

Inserting the graft

Bilateral nerve grafts can replace segments of erectile nerves if they need to be removed during a radical prostatectomy. Above, one graft has been attached; the second is nearly in position (at left). The tubing in the bladder opening will then be removed, and the bladder and urethra will be reconnected.

The first patients

Four months after surgery, the first patient, a 57-year-old married man, began noticing some improvement in erectile function. He couldn’t achieve an erection that was rigid enough for intercourse, but he did report “penile fullness.” After six months, nocturnal penile tumescence testing (NPT) showed two distinct erections that lasted for several minutes. (See “How NPT works,” below.) The patient used different devices, including a vacuum pump, to achieve an erection until, about 14 months after surgery, he was able to have an unassisted erection firm enough for intercourse. The second patient also experienced distinct erections, detected by NPT, just four months after his radical prostatectomy. These results were reported in 1999. (See “First reports on nerve grafts,” below.)

How NPT works

During nocturnal penile tumescence testing (NPT), a recording unit collects data on the number and duration of nocturnal erections, the change in the circumference of the penis, and penile rigidity. The measurements are made by two loops: one at the base of the penis and the other at the tip. Rigidity above 70% constitutes a nonbuckling erection; below about 40% represents a flaccid penis. During eight hours of sleep, three to six erections lasting 10 to 15 minutes each, on average, is considered normal, though definitions of “normal” vary.

The Texas team next reported on 12 patients who had had the nerve grafting procedure following the removal of the nerve bundles on both sides of the prostate (the experimental group). They compared the results in these patients with 12 patients who had had both cavernous nerves removed during a radical prostatectomy but declined to have sural nerve grafting (the control group).

After an average follow-up time of 16 months, four of the 12 men who had the grafting procedure could achieve an erection sufficient for sexual intercourse without medical devices or medications; five men had partial erections of 40% to 60%, and one had some fullness in the penis, but no erection. The other two men in the experimental group had no erectile response, though the researchers noted that it could take 24 to 36 months to realize the full benefit of the grafts. As expected, none of the men in the control group recovered natural erectile activity. Scores on various questionnaires given to both groups, such as the International Index of Erectile Function (IIEF), which measures the frequency and quality of erections as well as sexual desire and overall sexual satisfaction, were significantly lower among the men in the control group. Responses to questionnaires completed by partners of the men in the experimental group echoed what the men reported about their erectile function.

The group’s third study, which included 23 men, found that 26% of the men who had the nerve grafts were able to achieve unassisted erections firm enough for intercourse after an average of 23 months. Another 26% experienced partial erections, and 43% had erections sufficient for intercourse when they took the “little blue pill,” otherwise known as Viagra (sildenafil). Although the surgical time increased when men opted for a nerve graft, no significant problems related to the procedure occurred. However, a few men did report discomfort where the nerve was removed from the ankle and numbness on the side of the foot.

First reports on nerve grafts

Kim ED, Nath R, Kadmon D, et al. Bilateral Nerve Graft During Radical Retropubic Prostatectomy: 1-Year Follow-Up. Journal of Urology 2001;165(6 Pt 1):1950–56. PMID: 11371887.

Kim ED, Nath R, Slawin KM, et al. Bilateral Nerve Grafting During Radical Retropubic Prostatectomy: Extended Follow-Up. Urology 2001;58:983–87. PMID: 11744473.

Kim ED, Scardino PT, Hampel O, et al. Interposition of Sural Nerve Restores Function of Cavernous Nerves Resected During Radical Prostatectomy. Journal of Urology 1999;161:188–92. PMID: 10037395.

Subsequent research and positive findings

Research teams at other medical centers began to test the Texas group’s surgery to see if they could replicate the results. (See “Later reports on nerve grafts,” below.) Some performed the procedure in patients who needed only one graft, called a unilateral nerve graft, because surgeons had been able to spare one of the original cavernous nerves. For example, after an average of 16 months, four of 12 patients at Columbia University were fully potent following a unilateral nerve graft done at the time of surgery for prostate cancer or bladder cancer. One patient had partial erections. The only complication was a minor infection at the site of the ankle incision in one patient. Other findings:

  • In a Seattle study, 21 of 29 patients who had unilateral nerve grafting after a radical prostatectomy were able to have an erection sufficient for intercourse 19 months later, on average. Twenty-eight of the 29 reported numbness in their foot; one patient developed an infection at the incision site.
  • At another Seattle facility, researchers compared two groups of men: one group had a unilateral nerve-sparing prostatectomy and the nerve graft procedure, and the second group had just the unilateral nerve-sparing prostatectomy. After 24 months, the men who’d had the nerve graft had a greater rate of return of erectile function than those who’d had the unilateral nerve-sparing prostatectomy alone.
  • In a Japanese study, men who’d had the nerve graft procedure had a greater likelihood of urinary control in the year following a radical prostatectomy than those who’d had the unilateral nerve-sparing prostatectomy alone. However, men whose surgeons spared both nerve bundles during prostate surgery had the best urinary outcomes.
  • Patients who received a nerve graft taken from the thigh (a genitofemoral nerve graft) instead of the ankle were as likely to recover erectile function as those who received a sural nerve graft. Several men who had a genitofemoral nerve graft experienced chronic numbness in the thigh and scrotum following surgery.

Later reports on nerve grafts

Anastasiadis AG, Benson MC, Rosenwasser MP, et al. Cavernous Nerve Graft Reconstruction During Radical Prostatectomy or Radical Cystectomy: Safe and Technically Feasible. Prostate Cancer and Prostatic Diseases 2003;6:56–60. PMID: 12664067.

Hanson GR, Borden LS Jr., Backous DD, et al. Erectile Function Following Unilateral Cavernosal Nerve Replacement. Canadian Journal of Urology 2008;15:3990–93. PMID: 18405447.

Joffe R, Klotz LH. Results of Unilateral Genitofemoral Nerve Grafts With Contralateral Nerve Sparing During Radical Prostatectomy. Urology 2007;69:1161–64. PMID: 17572207.

Namiki S, Saito S, Nakagawa H, et al. Impact of Unilateral Interposition Sural Nerve Graft on Recovery of Potency and Continence Following Radical Prostatectomy: 3-Year Longitudinal Study. Journal of Urology 2007;178:212–16. PMID: 17499797.

Nelson BA, Chang SS, Cookson MS, Smith JA Jr. Morbidity and Efficacy of Genitofemoral Nerve Grafts With Radical Retropubic Prostatectomy. Urology 2006;67:789–92. PMID: 16584763.

Sim HG, Kliot M, Lange PH, et al. Two-Year Outcome of Unilateral Sural Nerve Interposition Graft After Radical Prostatectomy. Urology 2006;68:1290–94. PMID: 17141842.

Singh H, Karakiewicz P, Shariat SF, et al. Impact of Unilateral Interposition Sural Nerve Grafting on Recovery of Urinary Function After Radical Prostatectomy. Urology 2004;63:1122–27. PMID: 15183964.

Notes of caution

Despite the seemingly optimistic results, physicians and researchers suggest that patients think carefully and consider the potential downsides to the procedure, as well as the characteristics of their tumor, before jumping on the nerve graft bandwagon. In many of the early studies of nerve graft surgery, surgeons needed to remove both nerve bundles because of the extent of the cancer. However, surgeons have performed more and more nerve-sparing prostatectomies in recent years because cancers are more often detected and removed long before they impinge on the nerves.

Even in cases where only one nerve bundle can be spared, it’s difficult to know whether there is any benefit to a nerve graft. If a graft is done and erectile function returns, how does one determine whether the beneficial impact is due to the graft or the spared nerve? In 2008, Chicago researchers tried to answer this question by reviewing data on 1,175 patients who had a robot-assisted laparoscopic radical prostatectomy; of those patients, four had a bilateral sural nerve graft and 23 had the unilateral variety. The researchers found no statistically significant difference in the return of sexual function between those who had the unilateral graft and those who didn’t. They also found that candidates for the nerve graft had a greater risk of positive surgical margins and biochemical recurrence of their disease. Finally, they noted that none of the patients who had the bilateral nerve grafts regained sexual function. However, with only four patients in that group, definitive conclusions about the value of the procedure can’t be drawn.

Critics also point to the fact that only small, nonrandomized studies of unilateral nerve grafting have shown a benefit. Would the benefit hold in larger randomized controlled trials? Apparently not. Researchers at M.D. Anderson Cancer Center in Houston launched a randomized study in 2001 to determine whether having a sural nerve graft with a unilateral nerve-sparing prostatectomy would result in a 50% relative increase in potency after two years compared to having a unilateral nerve-sparing prostatectomy alone. All patients, regardless of the type of surgery they had, received penile rehabilitation therapy beginning six weeks after surgery. This therapy included taking 50 milligrams of sildenafil every other day, using a vacuum erection device five times a week, and receiving a penile injection twice a week to help spur an erection. Follow-up evaluations occurred every four months for two years.

But in May 2006, the researchers closed the trial. An interim analysis of the data they had collected showed that continuing with the trial would be futile because they would not be able to show a 50% relative increase in potency with sural nerve grafting. Among patients who completed the two-year study, 71% of those who’d had the nerve graft recovered potency versus 67% of the controls — not a statistically significant finding. Furthermore, the researchers found no differences in the amount of time it took study participants to regain sexual function. (To read this study on your own, see “Clinical trial halted.”)

Clinical trial halted

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. European Urology 2009;55:1135–43. PMID: 18783876.

A few other points to consider:

  • Because the procedure is considered experimental, your insurance company probably won’t cover the cost. Many urologists and surgeons haven’t been trained in nerve grafting, so you may need a plastic surgeon or neurosurgeon to harvest the graft, which will mean a higher price tag. Expenses may be covered, however, if you have the procedure as part of a clinical trial. (See “Clinical trials,” below.)
  • The nerves and blood vessels that run alongside the prostate gland form an intricate network. Furthermore, the nerves don’t follow a straight line — they branch and fan out, especially at the ends, making a precise graft nearly impossible. Even in cases where patients have regained erectile function, they report that the quality of the erection is not what it was prior to surgery.
  • The nerve grafting procedure adds quite a bit of time to a radical prostatectomy. In addition, because the surgeon needs to remove the nerve graft from the ankle (or another site), the patient is likely to lose more blood. None of the studies highlighted here noted any problems associated with blood loss, but it does remain a distinct possibility.
  • Side effects and complications beyond those associated with a traditional radical prostatectomy are possible. These include numbness at the graft site, nerve damage, and infection.

Clinical trials

When this article was written in 2009, no clinical trials of sural nerve grafts were under way, according to the National Institutes of Health listing of clinical trials. However, a corporation-sponsored trial of a nerve tissue scaffold created from human tissue was enrolling patients. Instead of receiving one of their own nerves, patients in this trial will receive tissue from another person that has been “cleaned” of that person’s cells; the remaining scaffolding provides a structure through which nerves can grow. As a result, patients wouldn’t need a second incision to remove a nerve and could avoid feelings of numbness later. For more information on this trial, log on to www.clinicaltrials.gov, and search for “nerve graft” and “prostate cancer.”

Given the experimental nature of the procedure and the other downsides, most experts don’t endorse nerve grafting for the average patient. Although the procedure is technically feasible, they say that a patient’s best bet is to find an experienced urologist with an excellent track record at removing the tumor and preserving one or both nerve bundles. After that, talk with your doctor or a specialist about how penile rehabilitation may help you recover sexual function.

Originally published Oct. 1, 2009; Last reviewed April 11, 2011

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