Objectives. To evaluate, using five experienced surgeons, the efficacy of the first-generation Cavermap Surgical Aid to identify the cavernous nerves intraoperatively and to predict the recovery of sexual function. This study was not designed to determine whether this device improves the ability to preserve the nerves or improve outcome.

Methods. Fifty men younger than 60 years old (mean age 52.5 years; range 43 to 59) with clinically localized prostate cancer (76% T1c, mean Gleason score 6, prostate-specific antigen level less than 10 ng/mL) underwent nerve-sparing radical prostatectomy (90% bilateral). Intraoperatively, the Cavermap device was used to test for the presence of the cavernous nerves once the neurovascular bundle was identified visually and to determine whether the nerves were intact after the prostate was removed. Erectile function was evaluated using the International Index of Erectile Function; men were considered potent if they were able to achieve unassisted intercourse in at least one half of their attempts.

Results. Before the removal of the prostate, the tumescence response to stimulation of the neurovascular bundle was 87.8%; when tissue not containing the neurovascular bundle was stimulated, no tumescence response occurred in 54%. After prostatectomy. a bilateral response to stimulation occurred in 90%, a unilateral response in 5%, and no response in 5%. Postoperatively, 71% of the patients were potent at 12 months. In the patients who demonstrated bilateral stimulation after removal of the prostate, 78% were potent at 12 months.

Conclusions. After radical prostatectomy performed by experienced surgeons, patient-reported potency rates in men younger than 60 years of age were high. Cavermap stimulation demonstrated an 87.8% sensitivity and 54% specificity in locating the neurovascular bundle as identified by experienced surgeons. The lack of specificity of this first-generation device limits its application for deciding which structures can be safely preserved or excised. Because virtually all patients demonstrated a positive response after removal of the prostate, the value of stimulation to predict the recovery of sexual function is yet to be determined. UROLOGY 57: 491-494, 2001. © 2001, Elsevier Science Inc.

This study was supported by a grant from UroMed Corporation, Norwood, Massachusetts.

Submitted: April 13, 2000, accepted (with revisions): November 10, 2000

The development of nerve-sparing anatomic radical retropubic prostatectomy made it possible to reduce the likelihood of postoperative impotence, one of the major side effects that has limited the widespread adoption of surgery as the preferred form of treatment for localized prostate cancer. The surgical technique is based on the discovery that the branches of the pelvic plexus that innervate the corpora cavernosa (cavernous nerves) travel outside the capsule and fascia of the prostate.¹ The identification of these nerves at the time of surgery was facilitated by the observation that these nerves travel in rather constant association with the capsular arteries and veins of the prostate, forming a neurovascular bundle that provides the macroscopic landmark for the identification of these nerves intraoperatively.² Using this procedure, experienced surgeons from three high-volume academic medical centers have reported potency rates of 62% to 68%.^3-6 However, these favorable outcomes have not been universal. A number of centers have met with far less success, reporting potency rates of only 10% to 30%.^7-10 It is generally recognized that nerve-sparing anatomic radical prostatectomy is a technically challenging operation. Although the reason for the variability in results from various centers is not entirely clear , it may relate to the ability of experienced surgeons to identify and preserve the cavernous nerves.¹¹

Recently, a new surgical tool, the Cavermap Surgical Aid (UroMed, Norwood, Mass) has been developed to assist in the identification of the cavernous nerves.¹² This surgical aid is a combined nerve stimulator and tumescence monitoring device that can detect tiny increases or decreases in penile tumescence (0.5%) that cannot be recognized visually. On the basis of the presence or absence of a response, it is possible that using this device, less experienced surgeons may be able to make more informed decisions regarding the strategy for optimal preservation of the neurovascular bundles.

This technique underwent a preliminary evaluation, the results of which suggest its efficacy in improving the results of nerve-sparing radical prostatectomy.¹³ In a single-blind, multicenter study, 61 patients were randomized intraoperatively to Cavermap nerve-sparing versus conventional nerve-sparing surgery. At 6 months of follow-up, erections were reported in 60% of the Cavermap group versus 45% of the conventional nerve-sparing group.

In an effort to determine whether Cavermap stimulation correlates well with the visual identification of the neurovascular bundle by experienced surgeons, this study was undertaken. Specifically, five experienced surgeons used the device to determine how well it correlated with their visual identification of the neurovascular bundle before removal of the prostate. After prostate removal, the presence or absence of the neurovascular bundle as deterolined by visual inspection or Cavermap stimulation was correlated with sexual function 12 months postoperatively. This study was not designed to determine whether the use of the Cavermap improved the ability to preserve the nerves or improve outcome.

Five urologists from high-volume centers of excellence for prostate cancer screened and enrolled approximately 10 patients (each center) into the study. Subjects and their partners provided signed informed consent. The entry criteria were as follows: patients younger than 60 years of age with clinically localized prostate cancer (clinical Stage Tlc-T2b, Gleason score less than 8, prostate-specific antigen level less than 10 ng/mL) who were undergoing radical prostatectomy and who had a sexual partner. Erectile function was assessed preoperatively by patient self-report using the International Index of Erectile Function (IIEF).¹⁴ Subjects were required to have a sexual partner. To be included in the study, subjects were required to answer questions regarding their ability to get an erection (question 1), ability to have an erection sufficient for penetration and to be able to penetrate their partner (questions 2 and 3), and ability to maintain an erection to the completion of intercourse (questions 4 and 5). The eligibility for enrollment required responses of "most times," "almost always," "slight difficulty," or "no difficulty." In response to question 14, "How satisfied have you been with your sexual relationship with your partner," they had to answer "high" or "very high." The exclusion criteria included subjects with cardiopacing equipment or other electromechanical prosthetic devices, subjects who had undergone previous surgery within the past 6 months that could affect sexual function (ie, transurethral resection of the prostate), subjects who used neoadjuvant hormonal therapy, subjects receiving antihypertensive medications that had been changed within the past 6 months, and subjects with diabetes, significant neurologic disease, major psychiatric disorders, or disorders that, in the opinion of the investigator, might be considered life-threatening within 2 years.

At the time of surgery, investigators were asked to identify the anatomic location of the neurovascular bundle.⁵ Cavermap stimulation was used as previously described to evaluate these regions before the neurovascular bundle was mobilized.^12,13 Stimulation and monitoring were also performed after removal of the surgical specimen to ascertain whether the nerves had been preserved and were functional.

Patients were evaluated by the study coordinator at 3, 6, and 12 months postoperatively by mail, in person, or by telephone regarding their serum prostate-specific antigen level; assessment of erectile function using the IIEF (administered to both the subject and his partner); use of erectile aids, concomitant medications, and treatments; assessment of urinary continence; and assessment of any adverse events that may affect erectile function. Originally, 56 patients were recruited to the study, but only 50 were available for evaluation. In 2 patients, the operative data were incomplete; in 1 patient, marked scar tissue from a prior pelvic fracture and bladder rupture was present and the investigator believed that an adequate operation could not be performed; 1 patient underwent adjuvant radiotherapy; 1 patient did not return the information; and 1 subject withdrew consent.

The mean age was 52.5 years (range 43 to 59), the mean Gleason score was 6, and 38 patients had Stage T1c disease and 12 patients Stage T2a or T2b disease. The postoperative pathologic stage was organ confined in 38 (76%), capsular penetration in 8 (16%), and positive seminal vesicles in 4 (8%); 5 patients had positive surgical margins (10%).

In these 50 patients, the neurovascular bundle was identified by the investigator at 336 sites; positive stimulation was recorded in 295 (87.8%). The nature of the tumescence response was an increase in tumescence in 6.4%, a decrease in tumescence in 32.2%, and a decrease preceded or followed by an increase in 60.4%. In 54 anatomic sites, the investigator stated that the neurovascular bundle was not present (anterior bladder/prostate); this was confirmed by a lack of stimulation (tumescence or detumescence) in 29 (54%). This resulted in a sensitivity of 87.8% and specificity of 54%.

The neurovascular bundles were preserved bilaterally in 45 patients (90% of the cases). In 5 men (10%), the neurovascular bundles were either partially or widely excised on one side. In patients in whom the investigator believed that the neurovascular bundles had been preserved on both sides, postoperative stimulation was present on both sides in 93%, on one side in 5%, and on neither side in 2%. In the 5 patients in whom the surgeon believed that the neurovascular bundle was either partially or widely excised on one side, stimulation occurred on both sides in all cases.

Postoperatively, patients were considered to be potent if they were able to have unassisted intercourse with or without sildenafil in at least one half of the attempts. Sixty percent of the patients used sildenafil. At 12 months, 71% of the men were potent; in men using sildenafil, 75% were potent. At 12 months, the IIEF score (mean + SD) for questions 3 and 4 for men not using sildenafil was 3.1 + 1.5 and 3.1 + 1.6, respectively. For men taking sildenafil, the responses were 3.5 + 1.4 and 3.6 + 1.4. In patients who had a positive response to stimulation on both sides after removal of the prostate, 78% were potent at 12 months.

The results of this study demonstrate the ability of the Cavermap device to induce a response (tumescence or detumescence) after stimulation of the neurovascular bundles. It is interesting to note that stimulation resulted in tumescence alone in only 6% of the stimulations. This suggests that electrical stimulation of the cavernous nerves frequently results in detumescence, which may explain why it has been so difficult to use intraoperative stimulation as a surgical aid. Although the device proved to be quite sensitive in the identification of the cavernous nerves, it also had rather low specificity (54%). It was hoped that this device would provide an accurate method for less experienced surgeons to improve their potency outcomes after radical prostatectomy. Unfortunately, this lack of specificity suggests that one cannot reliably depend on the results to make intraoperative decisions concerning whether a structure can be safely preserved or excised. The reason for this lack of specificity most likely relates to the spontaneous changes in penile tumescence that occur during surgery, secondary to traction on the prostate. On the basis of the observations in this study, a second-generation device has been developed that evaluates whether spontaneous tumescence or detumescence is occurring before stimulation so that a more stabile baseline can be established immediately before stimulation.

Postoperatively, 71% of the patients in this study had recovered sexual function at 12 months. This finding correlates very closely with a recent patient-reported outcome study that was carried out in a similar group of patients in which 73% of the men were potent at 12 months.^ll Together, these studies suggest that nerve-sparing radical prostatectomy performed by experienced surgeons results in excellent preservation of sexual function in men younger than 60 years old. Because both of these studies used patient-reported outcomes collected confidentially by an independent third party, it refutes the commonly held belief that the results at centers of excellence may be unreliable because patients may try to minimize adverse outcomes when speaking directly to their physicians or that surgeon interviewers may try to minimize adverse outcomes.^9,10

A major objective of this study was to determine whether stimulation of the cavernous nerves after removal of the prostate would predict the long-term recovery of sexual function. Unfortunately, we are unable to answer this question because virtually all patients demonstrated bilateral stimulation and the only patient who had no stimulation did not return his questionnaire at 12 months.

With the earlier diagnosis of prostate cancer, more young men with organ-confined disease are being identified. For this reason, improvements in surgical technique and in surgical aids for the identification of the neurovascular bundles intraoperatively should be of high priority. Recognizing that sildenafil is only effective in patients who have undergone successful nerve-sparing procedures is an added impetus for these efforts.¹⁵

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15. Zippe CD, Kedia A W, Kedia K, et al: Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate. Urology 52: 963-966,1998.