Early Experience with Intraoperative Cavernous Nerve Stimulation with Penile Tumescence Monitoring to Improve Nerve Sparing during Radical Prostatectomy

LAURENCE KLOTZ AND SENDER HERSCHORN 

ABSTRACT

Objectives. To determine if intraoperative stimulation of the cavernous nerves while monitoring changes in penile tumescence to map the course of these nerves would result in an improvement in nerve sparing and erectile function after radical prostatectomy.

Methods. Patients were eligible for this pilot study if they were undergoing a radical prostatectomy and were candidates for a nerve-sparing approach. Erectile function was assessed by patient self-reporting and questionnaire before surgery and by patient self-reporting periodically 12 months after surgery. A cavernous nerve stimulator and tumescence-monitoring device was used during radical prostatectomy to identify the course of the cavernous nerves and guide the surgeon in avoiding nerve damage. Patients were monitored for any evidence of complications and/or adverse events for 1 year from time of surgery.

Results. Twenty-six patients were recruited to the trial. Nerve stimulation and tumescence monitoring was performed in 23 patients. Twenty-one of 23 patients demonstrated a tumescence response to intraoperative nerve stimulation. Nineteen of 21 patients reported erectile function preoperatively. Seventeen (89%) of 19 patients demonstrated a tumescence response during surgery. Sixteen (94%) of the 17 patients who demonstrated a response to nerve stimulation and for whom the surgery was guided by the tumescence response reported the ability to have erections after surgery. No side effects due to the use of the device were reported. Only 3 (12%) of 25 patients had positive margins confined to the lateral margin and/or apex whose modifications associated with nerve sparing could conceivably have altered margin status.

Conclusions. These clinical data suggest that an intraoperative tumescence response to cavernous nerve stimulation may guide the surgeon in preserving cavernous nerves and improving erectile function after radical prostatectomy.  UROLOGY 52: 537-542, 1998. © 1998, Elsevier Science Inc. All rights reserved.

The anatomic radical retropubic prostatectomy has resulted in unprecedented enthusiasm for surgical extirpation of prostate cancer. The appeal of this approach relates to improved rates of erectile dysfunction and incontinence. However, re­ported rates of these important long-term morbidities cover a broad range. In particular, the reported rate of erectile failure after radical prostatectomy varies from 30% to 100% in physician-reported series¹ and in 11% to 86% of cases as mea­sured by patient questionnaire.¹

The technical modifications directed toward preservation of erectile function depend on the surgeon's ability to remove cancerous tissue while sparing the cavernous nerves.² In appropriately se­lected patients (early clinical stage, low Gleason score, low serum prostate-specific antigen [PSA]), the positive surgical margin rates using the ana­tomic approach are reported to be equivalent to that of conventional prostatectomy. 3-5  

Difficulty in locating the neurovascular bundles containing the cavernous nerves may occur as a consequence of the following: (1) variation in location of the cavernous nerve,⁶ (2) the presence of overlying tissue, (3) blood obscuring the surgical field, or (4) poor exposure due to bodily habitus.⁷ An initial intraoperative experience using cav­ernous nerve stimulation with tumescence moni­toring has been reported.⁵ A tumescence response was obtained consistently during surgery. The out­come with respect to erectile function was not de­scribed.

More accurate intraoperative identification of the neurovascular bundles may likely improve the rate of erectile potency after radical prostatectomy. This report describes preliminary experience and results of surgery with regard to erectile function using a new technology that stimulates the cavern­ous nerve while monitoring penile tumescence (Cavermap; Blue Torch Corporation, Boston, Mass) during radical prostatectomy.

MATERIAL AND METHODS

Eligible patients were men who required radical prostatectomy procedures, agreed to participate in this trial, and were candidates for a nerve-sparing approach. Patients were se­lected for favorable to intermediate prostate cancer, Stage T1c or T2a-c, Gleason score less than 8, and PSA less than 15. Erectile function was assessed by patient self-reporting and questionnaire before surgery and by patient self-reporting pe­riodically 12 months after surgery. Erectile function before and after surgery was categorized as full, partial, or none. Full erectile function was defined as the ability to consistently achieve erections sufficient for penetration. Partial erectile function was characterized by the occurrence of erections but the inability to consistently achieve erections sufficient for penetration. No erectile function was defined as the absence of full or partial erections.

This was an initial pilot feasibility study, the primary end point of which was the induction of penile tumescence by proximal cavernous nerve stimulation after removal of the prostate. The secondary end point was postoperative erectile function evaluated by patient questionnaire. Exclusion crite­ria included cardiac pacing equipment or other electrome­chanical prosthetic devices, prior pelvic radiation therapy, or neoadjuvant therapy more than 3 months before surgery.

SURGICAL PROCEDURE

General anesthesia was induced and maintained using a conventional approach, at the discretion of the anesthetist. Neuromuscular blockade was used routinely. The Blue Torch CaverMap device was used for nerve stimulation and tumes­cence monitoring. Standard technique for radical prostatectomy with nerve sparing was performed.⁹ Nerves were identi­fied by placing the electrode tip of the nerve stimulator above the suspected nerve. The stimulator was used in both the coarse (eight electrodes) and fine mode (between one and four electrodes). Stimulation was accomplished by inducing a biphasic current pulse train for up to 80 seconds with a con­trolled current intensity (1 to 20 niA) and pulse duration of 800 microseconds.

Stimulation was attempted at the left and right cavernous nerve regions as depicted in Figure 1. Initial nerve stimulation was performed on each side posterolateral to the urethroprostatic junction (baseline) after division of the urethra. If no tumescence response occurred, the stimulation procedure was discontinued. If a tumescence response occurred, the tissue at the site of stimulation was spared, and the lateral pedicle was mobilized closer to the prostate, taking care to remain extra-capsular. Where the stimulation of the pedicle produced a tumescence response but mobilization closer to the prostate would have transgressed the capsule or palpable cancer, the pedicle was ligated and divided independent of the tumes­cence response. The time of stimulation relative to the operative time, number of attempts of stimulation, and changes in tumescence were recorded electronically by the device.

FIGURE 2. Tumescence response to cavernous nerve stimulation. The left Y-axis (tumescence) represents the circumference of the patient's penis. During this series of three stimulation attempts, the tumescence baseline was 10.6cm and increased to 10.8cm (1.9% change). The right Y-axis (current) represents the current inten­sity in milliamperes (mA). The initial stimulation level was 8 mA and automatically increased to 10 mA after 20 seconds. Stimulation was discontinued when in­creasing tumescence was identified to avoid fatiguing the response.

A sample graph of tumescence response to cavernous nerve stimulation during radical prostatectomy using the device is shown (Fig. 2). The graph details the current delivered, the time the current was delivered, and the resultant tumescence response. The device is programmed to provide a gradual in­crease in current (from 8 to 20 mA) in 20-second increments. In responding patients, the result was a change in tumescence relative to the baseline established before each stimulation. The graph also shows the cessation of current increase after a 50/o positive tumescence response was reached. On the basis of the initial clinical experience, a minimum change in tumes­cence of 0.5% was considered a tumescence response. To avoid fatiguing the erectile response, stimulation was discon­tinued once an unequivocal response was elicited. No attempt "'as made to determine 'maximal response."

Patients were monitored for any evidence of complications and/or morbidity from the time of surgery up until the last recorded follow-up communication.

RESULTS

A total of 26 men, aged 57 to 71 years (median 63), participated in the trial. In 23, nerve stimula­tion was used. Grade and stage of prostate cancer are indicated in Table I. Three patients who received 8 to 12 weeks of neoadjuvant androgen ab­lation before surgery were included to determine if the technique could be used in the neoadjuvant setting.

Erectile function is reported for 19 previously potent patients who indicated erectile function preoperatively, where the device was used throughout the surgery, and 1 year of follow-up is available. Seven patients participated in the study but were not eligible for comparative evaluation of erectile function. These consisted of the following:

(1) 3 patients who did not have the stimulator used because of either obvious gross extracapsular dis­ease, making a nerve sparing operation ill-advised (n = 1), or technical difficulties with the device (n = 2); (2) 2 patients who had erectile failure before surgery and were studied as controls; (3) 1 patient, potent before surgery, who was found at surgery to have metastatic disease in lymph nodes, was placed on androgen ablation and has been ex­cluded from the analysis of postoperative erectile function; and (4)1 patient whose erectile function data were not available after surgery.

STIMULATED GROUP

Twenty-one of 23 patients demonstrated a tu­mescence response to intraoperative nerve stimu­lation (Table II). All 3 patients treated with neoad­juvant therapy before surgery demonstrated a response.

The median time required to elicit a tumescence response after stimulation was 20 seconds. Device setup and use added approximately 10 to 15 min­utes to the operative time and was considered non­significant in terms of patient recovery. There was no apparent effect on blood loss, postoperative re­covery, or average length of stay in hospital.

Nineteen of the 21 patients reported erectile function preoperatively. Seventeen (89%) of the 19 patients demonstrated a tumescence response dur­ing surgery, thus permitting modilication of the surgical dissection to preserve the path of the cav­ernous nerve identified by stimulation (Table Ill). After surgery, 16 (84%) of the 19 patients in the device group reported the ability to have erections (Table III). Five (31%) reported recovery of con­sistent full erectile function, and 11(58%) patients reported inconsistent or partial erectile function. Three (16%) patients had no erectile function post­operatively

Sixteen (94%) of the 17 patients who showed a tumescence response to nerve stimulation re­ported erectile function after surgery. The 2 pa­tients who did not exhibit a tumescence response intraoperatively did not recover erectile function after surgery.

Four of the 5 patients who recovered full erectile function showed a positive tumescence response to stimulation during surgery. The fifth patient expe­rienced a detumescence response (contraction of penis in response to stimulation) during surgery. All 11 patients who reported partial erectile func­tion showed a positive tumescence response to nerve stimulation. Of the 3 evaluable, previously potent patients who did not recover erectile func­tion, 1 patient showed a response to nerve stimu­lation, and 2 patients showed no response.

In the stimulated group, there was a correlation between age and postoperative potency that did not reach significance. Median age in the groups with normal erections, partial erections, and no erections was 58, 65, and 62 years, respectively (P = 0.134).

NONSTIMULATED GROUP

As described, the device was not used as planned for 3 patients. Although all 3 patients reported erectile function before surgery, none have had erections after surgery.

GROUP WITH ERECTILE FAILURE PREOPERATIVELY

Two control group patients reported no erectile function before prostatectomy and were studied as control subjects. In both patients, tumescence re­sponses were elicited during the procedure but they had erectile failure postoperatively.

PATHOLOGIC FEATURES

The prostate cancer was excised with negative margins in 21(84%) of the 26 cases. Of the 5 cases with positive margins (Table IV), 2 had extensive disease with seminal vesicle or multiple areas of positive margins, and 3 (12%) had positive mar­gins at the apex and/or lateral margin only. Of these 3, 1 had a Gleason score of 8 and 1 had a PSA greater than 10. The nerve locator device had been used in all 5 positive margin cases.

COMPLICATIONS AND/OR MORBIDITY

Three patients had complications of intermediate or serious severity (bladder neck contracture [n = 2]; excessive blood loss greater than 2000 [mL 1]). None of these events was related to the use of the nerve locator device.  

COMMENT  

Erectile failure after radical prostatectomy is multifactorial. Postoperative potency reflects a number of factors, including the number of neurovascular bundles spared, age, and level of preoperative sex­ual activity.'⁰ The heterogeneity of response to nerve sparing is supported by the correlation be­tween age and quality of postoperative erection seen in this study.

The CaverMap system was used to identify the location of the cavernous nerves during retropubic radical prostatectomy by monitoring tumescence response to intraoperative cavernous nerve stimu­lation. Sixteen (94%) of 17 patients with erec tile function before surgery who demonstrated a re­sponse to nerve stimulation and had surgery guided by the tumescence response reported the ability to have erections after surgery. Of 5 patients with erectile function before surgery who did not have the nerve stimulator used during prostate removal, none have the ability to have erections. There were no adverse events related to the use of the device.

lntraoperative nerve stimulation typically produces only a small erectile response, rather than a full erection. This is to be expected after stimulation of a single cavernous nerve fiber, because a normal erection requires coordinated signals over time through the plexus of cavernous nerves.

The tumescence monitor consists of a strain gauge placed around the base of the penis. It is capable of detecting a 0.5% increase in penile cir­cumference. Visually, this can be seen as a slight increase in penile girth and is frequently associated with contraction of the penile skin. This minimal increase in girth is significant only insofar as it indicates a response to nerve stimulation. A 0.5% increase in girth does not constitute an erection. Nonetheless, it is a guide to the existence of a neu­ral connection between the area being stimulated and the cavernous bodies.

This initial experience identified substantial het­erogeneity of response to nerve stimulation. Preop­erative potency was not required to produce an intraoperative tumescence response. Two patients who had erectile impotence preoperatively demon­strated a positive response. This is likely explained by the multifactorial nature of erectile impotence in many patients and the sensitivity of the tumes­cence monitoring. A patient with vasculogenic im­potence could still respond with a minimal in­crease in tumescence after cavernous nerve stimulation.

Two of 19 patients with normal erectile function failed to demonstrate a tumescence response. This may have been due to a variable course of the cav­ernous nerve, diffusion of current by blood at the site of stimulation, or misplacement of the elec­trode tip.

This device appears to facilitate accurate identi­fication of the location of the cavernous nerves. Once the locations of the nerves are clearly identi­fied, it is possible to make a more informed deci­sion about the optimal site of resection (balancing the goals of a negative resection margin and pres­ervation of the neurovascular bundle).

The presence of a positive surgical margin con­fined to the apex and/or lateral margin in only 12% of patients suggests that the risk of compromise of surgical margins as a result of the nerve-sparing technique is a minor one. This compares favorably to the rate of margin positivity in this region (27%) reported by others." With this relatively small se­ries, an analysis regarding the impact of the tech­nique on the rate of margin positivity is not possi­ble. There is no evidence that the rate of margin positivity is any higher than with the conventional nerve-sparing approach. Appropriate patient selec­tion is clearly required to identify candidates for this procedure and guide surgical technique. Uni­lateral cavernous nerve sparing, for example, may be indicated in patients with a T2 nodule; wide surgical margins with deliberate sacrifice of the cavernous nerves bilaterally is appropriate for pa­tients with palpable high-grade tumors.

This was a pilot study in a limited number of patients whose erectile function was evaluated in a subjective fashion-by patient self-reporting. Nocturnal tumescence monitoring would have provided more objective evidence of preservation of potency but was not deemed feasible for this initial pilot study. Nocturnal tumescence monitor­ing has been incorporated into the randomized prospective trial of this technique, which is cur­rently underway.

The rate of potency sparing in patients undergo­ing a conventional nerve-sparing procedure with­out the use of this device by the surgeons involved in this study is approximately 30% (full and partial erections) based on patient reporting. In most cases, this represented a partial erection only. The use of this nerve locator device resulted in an ap­parent improvement in erectile function postoper­atively compared with our prior experience.

CONCLUSIONS  

This early experience suggests that a tumescence response to cavernous nerve stimulation during surgery may aid the surgeon in locating and ulti­mately preserving cavernous nerves. This has ap­peared to translate into an improvement in erectile potency 1 year after radical prostatectomy. A multicenter, blinded, randomized, prospective trial with objective and validated assessments of erectile potency and sexual function that will test the utility of the CaverMap system (Figs. 3 and 4) is currently underway.

REFERENCES

1.  Hendricks JG, and Kaplan SA: What the literature re­veals about the complications of radical retropubic prostatectomy. Contemp Urol 13-22, January 1997.

2. Walsh PC, Lepor H, and Eggleston C: Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 4: 473-485, 1993.

3. Bigg SW: Role of nerve sparing radical prostatectomy for clinical stage B2 prostate cancer.] Urol 144:1420-1424, 1990.

4. Quinlan DM, Epstein JI, Carter BS, et ol: Sexual func­tion following radical prostatectomy: influence of preserva­tion of neurovascular bundles.] Urol 145:998-1002,1991.

5. Walsh PC: Potency following radical prostatectomy with wide unilateral excision of the neurovascular buiidle. J Urol 138: 823-827, 1987.

6. Myers RP: Radical prostatectonly: pertinent surgical anatomy. Urol Clin North Am 2:1-18, 1994.

7. Lue TF, Gleason CA, Brock GB, et al: Intra-operative electrostimulation of the cavernous nerve: technique, results and limitations.] Urol 154:1426-1428, 1995.

8. Watson Dl, Richie ]P, Vickers MA, et ol: Cavernosal nerve stimulation during radical retropuhic prostatectomy (abstract).. Proc AUA 153: 383A, 1995.

9. Walsh PC: Anatomic radical retropubic prostatectomy, in Walsh PC, Retik AB, Vaughan ED, et ol (Eds): Comphell's Urology. Toronto, WB Saunders, 1998, pp 2569-2585.

10. Stamey TA, and McNeal ]E: Adenocarcinoma of the prostate, in Walsh PC, Retik AB, Stanley TA, et ol (Eds): Camp­6ell's Urology. Toronto, WB Saunders, 1992, pp 1159-1221.

11. Catalona WS, and Bigg SW: Nerve sparing radical prostatectomy: evaluation of results after 250 patients.] Urol 143: 538-544, 1990.

EDITORIAL COMMENT

This article suffers from the usual problems of pilot studies (small numbers, use of nonvalidated questionnaires, failure to document previous success of nerve-sparing prostatectomy by the same surgeons, and failure to report unilateral versus bi­lateral cavernous nerve salvage). However, despite these shortcomings, the message delivered by the article is clear. if a device is available that allows the surgeon to "map" the course of the cavernous nerves during radical prostatectomy, an ex­tremely high degree of at least partial erectile capability can he achieved in patients by 1 year after surgery. The CaverMap device appears to allow the prostatectonly surgeon to achieve this objective. In more than 80% of cases in which intraoperative tumescence was generated by the device (so that cavern­ous nerve mapping could be achieved), at least partial erectile competence was experienced at 1 year after surgery in patients with a wide range of age and stage of disease. If this experience can be duplicated in a larger series, cavernous nerve mapping may become a standard part of anatomic radical prostatectomy.

Carl A. Ollson, A4.D. Atchley Pavilion  
161 Fort Washington Avenue New York, NY 10032  
REPLY BY THE AUTHORS

The comments by Dr. Ollson are appreciated. We empha­size that this was indeed an initial feasibility study. Further data are clearly required to confirm these results before this technology is incorporated into routine practice. A multi-center randomized trial comparing the use of this device with conventional nerve-sparing radical prostatectomy with objec­tive assessment of erectile function before and after surgery has been initiated by the authors.

Funding for this project was provided by Blue Torch, Inc., the spon­sor of the device mentioned in this article. None of the authors has any financial involvement relating to the device mentioned herein nor to the sponsor responsible for funding of this study.

From the Department of Surgery, University of Toronto, Division of Urology, Sunnybrook Health Science Centre, Toronto, Canada

Reprint requests: Laurence Klotz, M.D., Sunnybrook Medical Center, University of Toronto, 2075 Bayview Avenue, Room MG408, Toronto, Ontario M4N 3M5, Canada

Submitted: April 17, 1998, accepted (with revisions): May29, 1998