Intraoperative nerve stimulation predicts postoperative potency

ADULT UROLOGY

INTRAOPERATIVE NERVE STIMULATION PREDICTS POSTOPERATIVE POTENCY SAM S. CHANG, MATTHEW PETERSON,

AND

JOSEPH A. SMITH, JR

ABSTRACT Objectives. Intraoperative nerve stimulation has been used to map the course of cavernosal nerve bundles to aid in nerve-sparing radical prostatectomy (RP). We sought to determine whether the intraoperative nerve stimulation response after removal of the prostate specimen predicts postoperative potency. Methods. We prospectively evaluated 63 consecutive patients undergoing RP. Among these 63 patients, 41 patients had a bilateral nerve-sparing procedure, and 22 underwent bilateral wide resection of the neurovascular bundles. Potency was determined at 1 year by direct patient interview. Results. Of the 22 patients with wide resection, 16 (73%) had no observed stimulated response, 4 (18%) had a measurable tumescence response, and 2 (9%) had detumescence. All 22 patients were impotent postoperatively. At a minimum follow-up of 1 year, of the 41 patients who underwent nerve-sparing RP, 27 (66%) had postoperative erections sufficient for penetration. Of the 30 men with an intraoperative stimulated tumescence response, 24 (80%) were potent; of the 6 with a detumescence response, 2 (33%) were potent; and of the 5 with no stimulated nerve response, 1 (20%) was potent. A tumescence response was significantly more predictive of postoperative potency than no intraoperative response (P ⫽ 0.017). Conclusions. An intraoperative tumescence response with stimulation of the neurovascular bundles after prostate specimen removal is more likely to correspond to successful postoperative sexual function after nerve-sparing RP than is no response. UROLOGY 58: 594–597, 2001. © 2001, Elsevier Science Inc.

A

natomic studies have defined the pelvic course of the cavernous nerves responsible for penile erection.1 On the basis of these studies, modifications in the surgical technique for radical prostatectomy (RP) have been developed that allow postoperative preservation of potency in some patients.2 Nonetheless, the course of the cavernous nerves and their relationship to the prostate and urethra varies, and this anatomic variability may be a factor in the sometimes less than favorable potency rates after nerve-sparing RP. Cavernosal nerve electrical stimulation has been reported in a limited number of patients undergoing retropubic RP.3–5 Use of the CaverMap (Uromed, Boston, Mass) nerve stimulator has been described as a method to map the course of the nerves during surgery and to facilitate preservation of the neurovascular bundle.5 The data regarding From the Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee Reprint requests: Sam S. Chang, M.D., Department of Urologic Surgery, Vanderbilt University Medical Center, A-1302 Medical Center North, Nashville, TN 37232-2765 Submitted: April 18, 2001, accepted (with revisions): May 29, 2001

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© 2001, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED

its usefulness, however, have been conflicting.5–7 Our own experience indicates that the lack of precision in the nerve-stimulating device and the variability in response limit its usefulness for intraoperative nerve mapping. Another issue, however, is whether the response after removal of the surgical specimen has any predictive value. Stimulation may test the integrity of the nerve fibers and provide prognostic information about the return of potency. We report what is, to our knowledge, the largest single-institution series of patients reported to determine the ability of intraoperative nerve stimulation after prostate removal to predict potency. MATERIAL AND METHODS Sixty-three consecutive patients undergoing retropubic RP for localized carcinoma of the prostate were evaluated prospectively using intraoperative nerve stimulation with the CaverMap surgical aid. The device consists of a control unit, a nerve-stimulating probe, and a strain gauge placed around the penis to measure changes in circumference. A light-emitting diode on the control unit called the tumescence response display indicates a tumescence or detumescence change in circumference that is equal to a 0.5% change (levels ⫾1 to ⫾4). A bilateral nerve-sparing approach was used in all T1c tu0090-4295/01/$20.00 PII S0090-4295(01)01310-3

mors, regardless of grade, if the man was potent preoperatively. Bilateral nerve sparing was also used for T2a tumors unless the palpable lesion seemed to be adjacent to the neurovascular bundle. The bundle was removed on the side of a palpable T2b tumor. A non-nerve-sparing approach was used in men who were impotent preoperatively. Surgery was performed through a lower midline abdominal incision, and general anesthesia was achieved using isoflurane and neuromuscular blockade. No patient in this study received an epidural catheter for anesthesia. After the prostate specimen had been removed, the response to postoperative stimulation of the neurovascular bundle was observed. Using the coarse mode, the tip was placed directly on the dissected neurovascular bundle. A graded increase in electrical current (up to 20 mA) occurs automatically with the CaverMap for a total of 45 seconds. Separate recordings were made for the right and left neurovascular bundles. The left bundle was always stimulated first so that any changes occurring as a consequence of the sequence of stimulation could be noted. Any measured, sustained change on the monitor screen of the device (graded to ⫾1 to ⫾4) was considered a positive response, and the greatest observed change was recorded. These levels on the device correspond to degree of penile circumference change (0.5%). A positive response on the monitor was a tumescence response, and any sustained negative reading was a detumescence response. If, after 45 seconds, no sustained response was observed, the patient was noted to have had no response. If the sides differed in response (which occurred in 3 of 42 patients), the response with the greatest change was noted. A unilateral response was noted as a response (2 of 42). Potency was determined by patient interview both preoperatively and postoperatively by the physician. Like previous investigators, for all patients, potency was defined as the ability to have erections sufficient for vaginal penetration more than 50% of the time intercourse was attempted.7 Patients were considered potent regardless of sildenafil use, but were not categorized as potent if they required the use of intracorporeal injections. Multiple comparisons between the intraoperative nerve responses were performed with the Fisher exact test.

RESULTS Sixty-three men with histologically confirmed adenocarcinoma of the prostate undergoing retropubic RP were included in this study. They ranged in age from 43 to 72 years (mean 59.8). Forty-one patients underwent a bilateral nerve-sparing dissection, and 22 patients had both nerves resected at prostatectomy because of a large volume or highgrade tumor. All patients had a minimum follow-up of 1 year, with a median of 14 months (Table I). Of the 22 patients with wide bilateral resection of the neurovascular bundles, all were impotent postoperatively. Most of these patients, 16 (73%), did not have a measurable stimulated response of either tumescence or detumescence. Despite wide resection, 4 (18%) of the 22 patients had measurable tumescence and 2 (9%) had detumescence. Of the 41 patients who underwent a bilateral nerve-sparing RP, 36 (88%) had an intraoperative response, either tumescence or detumescence, after removal of the prostate specimen. In these 41 patients, 27 (66%) had postoperative erections sufUROLOGY 58 (4), 2001

TABLE I. Patient characteristics Mean age (yr) Median follow-up (mo) Clinical stage (n) T1a T1b T1c T2a T2b Gleason score 2–4 5–6 7 8–10 Mean prostate-specific antigen (ng/mL)

59.6 (48–72) 14 (12–22) 1 2 41 12 7 4 47 10 2 8.4 (1.8–47)

Numbers in parentheses are the range.

ficient for penetration. Of these 27 patients, many (n ⫽ 14) were potent at 1 year without sildenafil use, but most (n ⫽ 23) took sildenafil during their follow-up. All men who were potent were 68 years old or younger. Thirty of the 41 patients had an intraoperative positive tumescence response after prostate removal. Twenty-four (80%) of these 30 patients were potent at a minimum follow-up of 1 year. Two (33%) of 6 patients who had a detumescence response were potent postoperatively. Of 5 patients who had no intraoperative response after bilateral nerve-sparing RP, only 1 patient (20%) was potent (Table II). The overall false-positive rate with a tumescence response was 29% (10 of 34). A tumescence intraoperative response after prostate removal was significantly more likely to predict eventual potency compared with no response (P ⫽ 0.017). Compared with detumescence, although tumescence was more likely to predict potency, this comparison did not reach statistical significance (P ⫽ 0.039). COMMENT The CaverMap device was developed to aid in identifying the cavernosal nerve bundles that contribute to potency and thus improve potency preservation at RP. The device stimulates the cavernosal nerves and measures small variations in penile girth that cannot be visually appreciated. The ability of this device to identify the often variable course of the cavernosal nerves and to improve potency is unclear. We reported marked variability with the CaverMap response with control stimulation at sites remote from the neurovascular bundle after producing a measurable response.6 In the 22 patients who underwent wide bilateral resection of the nerves, 6 patients (27%) still had a CaverMap 595

TABLE II. Intraoperative CaverMap response versus potency after nerve-sparing radical prostatectomy Total Non-nerve-sparing radical prostatectomy (n ⫽ 22) Potent Not potent Bilateral nerve-sparing radical prostatectomy (n ⫽ 41) Potent Not potent

Tumescence

No Response

0 22

0 4

0 2

0 16

27 14

24 6

2 4

1 4

response, belying the wide resection. In their early results, Klotz et al.8 reported an 84% potency rate with the aid of intraoperative stimulation. Their most recent Phase III analysis demonstrated improved erectile function by RigiScan in those patients who underwent nerve-sparing RP with the CaverMap device as opposed to those who underwent conventional nerve-sparing RP without the CaverMap. The sexual questionnaire results in their study, however, did not show a significant improvement in sexual function in patients in the CaverMap group compared with the control group.9 Although the device may have significant shortcomings in measuring the nerve course during dissection, we have demonstrated that a positive intraoperative tumescence response can accurately predict postoperative potency. Our study defined potency as the ability to maintain an erection adequate for 50% of sexual intercourse attempts. This definition differs from that of the National Institutes of Health Consensus Development Panel on Impotence, which defined erectile dysfunction as the inability of a man to achieve an erect penis as part of the multifactorial process of male sexual function.10 Our definition may be somewhat less strict, but has been used previously by others7 and applies to all our treatment groups. In addition, recent outcome studies evaluating erectile dysfunction have demonstrated that “success” for these patients is the ability to produce and maintain an erection satisfactory for intercourse.11 This definition does not diminish the predictive qualities of the device. During nerve-sparing RP, stimulated tumescence after prostate removal was associated with a return of potency and was a significantly better predictor for postoperative potency than no intraoperative stimulation response (80% versus 20%, P ⬍0.017). Thus, preservation of at least a portion of the nerve bundles as indicated by a tumescence response plays a role in potency recovery. Kim et al.7 examined 35 patients who underwent 596

Detumescence

bilateral preservation and 25 patients who underwent unilateral preservation and demonstrated no correlation between the intraoperative findings and postoperative recovery. Several explanations are possible for their contrasting conclusions. Their overall potency rate was relatively low (18%) and may have been due in part to the follow-up period (minimum 6 months, median 365 days), which was shorter than in our investigation. In addition, they included patients with unilateral nerve-sparing RP who interestingly were more likely to have a stimulated response than the bilateral nerve-sparing patients. Our definition of a positive intraoperative response also differed slightly.7 Although both tumescence and detumescence represent a “positive” response to intraoperative stimulation and are thought to represent intact neural function of the cavernosal nerves, in our comparison of tumescence versus detumescence, we found a significant difference between these responses. Postoperative potency correlated better with a tumescence response than with a detumescence response (P ⫽ 0.039). A detumescence response, in fact, did not differ significantly from no intraoperative response in predicting potency (P ⫽ 1.0). Although Klotz et al.9 did not directly compare detumescence versus no response, they also demonstrated that tumescence, not detumescence, was more likely to predict improved sexual function by questionnaire. An important caveat, however, is our small sample size, which may not have allowed us to determine a difference that may truly exist. An intraoperative tumescence response after removing the prostate, however, does not guarantee successful postoperative preservation of the nerves. When examining the entire cohort of patients, the false-positive rate was 29% (10 of 34) in patients with a tumescence response. In the bilateral nerve-sparing group, of the 30 patients with a tumescence response, a 20% false-positive rate still occurred. Perhaps if those patients with a weaker response (eg, ⫹1) were eliminated from the tumesUROLOGY 58 (4), 2001

cence group, a lower false-positive rate would result. We were, however, unable to determine whether this was the case with our small series. Although a lack of response did not preclude potency, we found, with a minimum 1-year followup, that it was highly unlikely that these patients will be potent. In our series, only 1 (5%) of 21 patients recovered their potency after having no stimulated intraoperative nerve response. Similarly, only a small percentage (25%) of patients with a detumescence response was potent postoperatively. As the National Institutes of Health Consensus Development Panel on Impotence stated, erectile dysfunction can depend on multiple components and factors. Defining potency after RP is difficult, and to determine the factors required to achieve a successful nerve-sparing technique is equally as difficult. We did not attempt to address this issue in this study as our patients described themselves as potent preoperatively. Our dissection technique and other factors such as age and baseline preoperative erectile function undoubtedly influenced the potency outcome, and on the basis of these factors, we can formulate a general probability of success after nerve-sparing prostatectomy. No individualized prediction of recovery, however, has been available prior to this device. Those patients who were impotent may in fact have been affected by poorer function preoperatively or may have had a more extensive dissection or may be older. Our data did not allow us to reconcile which factors played the key role, nor was this our purpose. Importantly, however, regardless of the different specific cause or combination of causes for a lack of recovery, we demonstrated that patients with no intraoperative response or a detumescence response were not likely to recover their potency. An intraoperative tumescence response predicted who would regain potency after nerve-sparing RP. Precise intraoperative dissection and preservation of the neurovascular bundles allow a substantial proportion of men, especially those of a younger age, to regain potency after retropubic RP. The variable course of the nerves, as well as the different anatomic configurations of the apical prostate, can influence the surgical results. Intraoperative nerve stimulation using the CaverMap has not proved to be of benefit in our hands for nerve mapping. We believe the broad area of stimulation provided by the tip and the variability in response limit the value of this device for precise intraoperative identification and dissection of the nerves.6 We have observed a clear correlation with the stimulated tumescence response after specimen removal with potency outcome. Most patients with a UROLOGY 58 (4), 2001

measured tumescence response regain adequate sexual potency, and the return of potency is unlikely with no measured response. Even though we were able to identify some correlation with the postdissection response and postoperative erectile function, in our opinion, the association is not sufficiently strong to predict results for every patient. As a result, we do not currently use the responses to determine or alter postoperative management. Although additional studies of this and similar devices should be encouraged, the variability in measurements limits any practical significant clinical role at this time. CONCLUSIONS Depending on the result, the CaverMap response can correlate with postoperative potency. Patients with no response or a detumescence response are unlikely to recover sexual function postoperatively. Those patients who undergo bilateral nervesparing RP and have a stimulated tumescence response are significantly more likely to be potent. Additional study with this device, however, is necessary to determine the clinical usefulness for each individual patient. REFERENCES 1. Walsh PC, and Donker PJ: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 128: 492– 497, 1982. 2. Walsh PC, Lepor H, and Eggleston JC: Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 4: 473– 477, 1983. 3. Lue TF, Gleason CA, Brock GD, et al: Intraoperative electrostimulation of the cavernous nerve: technique, results and limitations. J Urol 154: 1426 –1428, 1995. 4. Michl U, Dietz R, and Huland H: Is intraoperative electrostimulation of erectile nerves possible? J Urol 162: 1610 – 1613, 1999. 5. Klotz L, and Herschorn S: Early experience with intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy. Urology 52: 537–542, 1998. 6. Holzbeierlein J, Peterson M, and Smith JA Jr: Variability in results of intraoperative cavernous nerve stimulation during radical prostatectomy. J Urol 165: 108 –110, 2001. 7. Kim HL, Stoffe DS, Mhoon DA, et al: A positive CaverMap response poorly predicts recovery of potency after radical prostatectomy. Urology 56: 561–565, 2000. 8. Klotz L, Jewett M, Casey R, et al: A randomized phase 3 study of intra-operative cavernous nerve stimulation with penile tumescence monitoring (CaverMap) to improve nerve sparing during radical prostatectomy. J Urol 161: 335–338, 1999. 9. Klotz L, Heaton J, Jewett M, et al: A randomized phase 3 study of intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy. J Urol 164: 1573–1578, 2000. 10. National Institutes of Health Consensus Development Panel on Impotence: Impotence. JAMA 270: 83– 88, 1993. 11. Hanson-Divers C, Jackson SE, Lue TF, et al: Health outcomes variables important to patients in the treatment of erectile dysfunction. J Urol 159: 1541–1547, 1998. 597