When is it necessary to excise the nerves and are nerve grafts likely to improve sexual function in men undergoing Anatomic Radical Prostatectomy

Patrick C. Walsh, M.D.

Introduction
Men over the age of 50 who undergo preservation of both neurovascular bundles at the time of radical prostatectomy have a greater likelihood of recovering sexual function than men in whom it is necessary to excise one bundle widely. Men who undergo wide excision of both neurovascular bundles rarely, if ever, have spontaneous recovery. This raises the question of how often it is necessary to excise one or both neurovascular bundles widely at the time of surgery, and is it useful to use an interposition nerve graft in an attempt to restore sexual function in these patients.

Background
The neurovascular bundles are located outside the prostate and thus in patients with organ-confined cancer, both neurovascular bundles can be preserved safely. Furthermore, when prostate cancer extends beyond the prostate it usually travels only 1 or 2 mm away from the prostate before it extends toward the seminal vesicles. Thus in most patients who have capsular penetration it is still possible to preserve both neurovascular bundles without creating a positive surgical margin because the neurovascular bundles are located on average 5 mm from the prostate. Many urologists have the mistaken belief that the neurovascular bundle is the most common site of positive surgical margins and that if they excise the neurovascular bundle a positive margin will not occur. This is incorrect. The most common single sites of positive surgical margins, in order or frequency, are the apex (where the sphincter and urethra are attached), posterior (next to the rectum), and then posterolateral (near the neurovascular bundle). Thus, beware of the "knee-jerk" concept that the neurovascular bundle must always be excised on the side of the positive biopsy

How Often Is It Necessary To Widely Excise Both Neurovascular Bundles Widely?
I have always believed that if there was capsular penetration bilaterally to the point where it was necessary to excise both neurovascular bundles, the patient was not curable with surgery because he already had distant spread of tumor. In 2,700 radical prostatectomies performed between 1986 and 1999, 7 potent men had both neurovascular bundles excised. Four of these men were not cured because they had positive lymph nodes, positive seminal vesicles, or a positive margin elsewhere. In the other 3 it was not necessary because there was no capsular penetration on that side. Based on this experience I believe that it is almost never necessary to excise both neurovascular bundles. Well-meaning, but ill-informed urologists may believe that they are going to cure men better by excising both neurovascular bundles and placing nerve grafts. If these patients need both neurovascular bundles excised, I do not believe they are going to be cured, and if they don't need both neurovascular bundles excised they are going to benefit more from nerve-sparing than a nerve graft.

Is It Always Necessary to Excise the Neurovascular Bundle on the Side of the Positive Biopsy?
I recently reviewed 500 consecutive men who underwent radical prostatectomy between August 1997 and January 2000. At the time of surgery both neurovascular bundles were preserved in 87% of the patients and one neurovascular bundle was excised in 13%. The cancer was completely excised without any evidence of cancer at the edge of the margin (a positive margin) in 95% of the cases. A positive margin was present in 5% and was present only at the neurovascular bundle in 10 men (2%) and in half of these men the margin was positive on the side opposite the palpable lesion on the positive biopsy. Does that mean these patients weren't cured? No. Between 1982 and 1988 there were 25 men who had a solitary positive surgical margin at the neurovascular bundle. With followup greater than 12 years, 60% of these men have an undetectable PSA. Indeed, this freedom from recurrence is very similar to patients who had penetration through their capsule and negative surgical margins. Thus, in 500 consecutive men I do not believe that the patient's chances for cure were compromised by the surgical procedure. To accomplish this, however, one needs to be in the hands of an experienced surgeon who knows when and where to perform preservation or wide excision of the neurovascular bundle.

In this recent series of 500 patients who have been followed for at least 12 months, 64% of the patients with unilateral wide excision of the neurovascular bundle were potent postoperatively. The reported success with nerve grafts is 30% (see below). If a nerve graft had been performed in all of those patients it might have improved the recovery of sexual function to only 75%. However, I'm not convinced that it would have even worked that well. We previously analyzed the factors which influenced whether a man recovered potency following surgery. We found that patients who had capsular penetration or cancer involving the seminal vesicles were less likely to have recovery even if both neurovascular bundles were preserved. Thus, in these men who had advanced cancers requiring excision of one neurovascular bundle I'm not sure that a nerve graft would have improved sexual function.

Nerve Grafts
The first experimental work on the use of nerve grafts for restoration of sexual function was reported from the Brady Urological Institute in 1989. The rat proved to be an ideal model for these studies because the nerves responsible for erection are relatively large, distinct structures, much different from man where the nerves are a tiny plexus of multiple nerves surrounding vessels. Encouraged by these experimental studies, in 1991-92 I carried out a study of nerve grafts in patients who underwent wide excision of the neurovascular bundle. These procedures were performed in collaboration with a neurosurgeon. Unfortunately, with followup beyond 5 years there was no difference in the recovery of sexual function in patients who received a nerve graft and those who did not. Beginning in the early 1990's with the widespread application of PSA testing more men were identified with localized disease and as a result fewer men required wide excision of the neurovascular bundle. Discouraged by my initial results and with fewer patients requiring wide excision of the neurovascular bundle, I lost interest in nerve grafts.

Recently there has been revived interest in this topic. It has been reported that in men who underwent wide excision of both neurovascular bundles with placement of nerve grafts, 30% had recovery of sexual function. In reviewing these data I found out that 58% of the patients who underwent nerve grafts had no evidence of capsular penetration on either side and thus wide excision of the neurovascular bundles in these patients was not necessary. Furthermore, it is unknown whether the patients who recovered sexual function were the ones who benefited the most by having their nerves excised i.e. the ones with capsular penetration or the more favorable group where the tumor was organ-confined and wide excision was unnecessary. As pointed out earlier, wide bilateral excision of the neurovascular bundles is almost never necessary. However, if one neurovascular bundle is excised would the placement of a nerve graft help? The group that revived interest in nerve grafts states that when they excise one neurovascular bundle widely only 25% of their patients are potent. If they could improve the results by 30% then almost 50% of their patients might expect recovery of sexual function. For them this technique might be useful. However, at Hopkins without a nerve graft 64% of the patients who have one neurovascular bundle excised are potent. Also, it must be understood that nerve grafts are not without potential side effects such as the development of a small sensory defect on the side of the foot, the possibility of delayed ambulation, and the rare possibility of neuroma formation or reflex sympathetic dystrophy, in addition to the fact that the operation is prolonged with possible increased blood loss.

One needs to take all of these things into consideration before jumping on the nerve graft bandwagon.

Summary
I remain skeptical about the value of nerve grafts in restoring sexual function in men undergoing wide excision of the neurovascular bundle and am concerned that it may encourage urologists to pursue wide excision where it is neither necessary nor useful.

Patients who have invasion of the neurovascular bundle on both sides to the point where it is necessary to excise both neurovascular bundles are not curable with surgery.

Today most men with localized prostate cancer who undergo surgery can have preservation of both neurovascular bundles.

Patients who have extensive disease outside the prostate are less likely to recover sexual function regardless of the status of their nerves and are unlikely to benefit from placement of a nerve graft.

A randomized properly performed study of nerve grafts should be carried out before nerve grafts are widely accepted in the management of localized prostate cancer.

If it is likely that a patient will require excision of one neurovascular bundle the most valuable thing a patient can do to ensure the recovery of sexual function is to find a urologist who can precisely preserve the neurovascular bundle on the other side.

      REFERENCES

1. Walsh, P.C.: Anatomic radical prostatectomy: Evolution of the surgical technique. J. Urol. 160:2418-2424, 1998.
   
   
2. Walsh, P.C.: Radical prostatectomy, preservation of sexual function, cancer control: the controversy. Urol. Clinics of N. Amer. 14:663-673, 1987.
   
   
3. Walsh, P.C., Epstein, J.I., and Lowe, F.C.: Potency following radical prostatectomy with wide unilateral excision of the neurovascular bundle. J. Urol. 138:823-827, 1987.
   
   
4. Quinlan, D.M., Epstein, J.I., Carter, and Walsh, P.C.: Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J. Urol. 145:998-1002, 1991.
   
   
5. Quinlan, D.M., Nelson, R.J., and Walsh, P.C.: Cavernous nerve grafts to restore erectile function in a rat model. J. Urol. 141:186A, 1989.
   
   
6. Quinlan, D.M., Nelson, R.J., and Walsh, P.C.: Cavernous nerve grafts restore erectile function in denervated rats. J. Urol. 145:380-383, 1991.
   
   
7. Burgers, J.K., Nelson, R.J., Quinlan, D.M., and Walsh, P.C.: Nerve growth factor, nerve grafts and amniotic membrane grafts restore erectile function in rats. J. Urol. 146:463-479. 1991.
   
   
8. Quinlan, D.M., Nelson, R.J., Partin, A.W., Mostwin, J.L., and Walsh, P.C.: The rat as a model for the study of penile erection. J. Urol. 141:656-661, 1989.
   
   
9. Walsh, P.C.: Technique of vesicourethral anastomosis may influence recovery of sexual function following radical prostatectomy. Atlas Urol. Clin. N. Amer. 2:59-63, 1994.
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13. Walsh, P.C.: Radical retropubic prostatectomy. In Campbell's Textbook of Urology, 7th Edition, (eds)Walsh, P.C., Retik, A.B., Vaughan, E.D. Jr., Wein, A.J., W.B. Saunders, Philadelphia, pp. 2565-2588, 1998.Walsh, P.C., Donker, P.J.: Impotence following radical prostatectomy: Insight into etiology and prevention. J. Urol. 128:492-497, 1982.
    
    
14. Lepor, H., Gregerman, M., Crosby, R., et al: Precise localization of the autonomic nerves from the pelvic plexus to the corpora cavernosa: a detailed anatomical study of the adult male pelvis. J. Urol. 133:207-212, 1985. 13a.
    
    
15. Riopel, M.A., Polascik, T.J., Partin, A.W., Sauvageot, J., Walsh, P.C., and Epstein, J.I.: Radical prostatectomy in men less than 50 years old. Urol. Oncol. 1:80-83, 1995..
    
    
16. Holmes, G.F., Walsh, P.C., Pound, C.R., and Epstein, J.I.: Excision of the neurovascular bundle at radical prostatectomy in cases with perineural invasion on needle biopsy. UROLOGY 53:752-756, 1999.
    
    
17. Kim, E.D., Scardino, P.T., Kadmon, D., Slawin, K., and Nath, R.K.: Interposition sural nerve grafting during radical retropubic prostatectomy. UROLOGY (in press).
    
    
18. Pound, C.R., Partin, A.W., Epstein, J.I., and Walsh, P.C.: Prostate-specific antigen after anatomic radical retropubic prostatectomy. Urol. Clinics of N. Amer. 24:395-406, 1997.
    
    
19. Rabbani, F., Stapleton, A.M., Wheeler, T.M., Kattan, M.W., Scardino, P.T.: Predicting recovery of erectile potency after radical prostatectomy: Influence of age, preoperative potency, and extent of nerve-sparing. J. Urol. 163 suppl:2