A Randomized Phase 3 Study of Intra-Operative Cavernous Nerve Stimulation with Penile Tumescence Monitoring (CaverMap™ Surgical Aid) to Improve Nerve Sparing During Radical Prostatectomy

Laurence Klotz, Michael Jewett, Richard Casey, Toronto; Jeremy Heaton, Kingston; Joseph Chin, London; Larry Goldenberg and Martin Gleave, Vancouver, Canada (presented by Dr. Klotz)

Introduction:

The reported rate of erectile failure following radical prostatectomy varies from 30-100% in physician-reported series' and 11-86% of cases as measured by patient questionnaire. Bilateral nerve sparing yields higher rates of return of function than unilateral sparing for patients where both bundles have been removed have the lowest rates of erectile function. Recent reports on the benefits of Sildenafil to treat ED following radical prostatectomy demonstrated that 80% of patients with bilateral sparing respond to the drug, while a lesser proportion of patients with unilateral sparing and no patients with both nerves transected benefit.² Thus, even with the new pharmaceuticals, effective nerve sparing contributes substantially to the return of erectile function following radical prostatectomy. Although cavernous nerve sparing techniques have become standard procedures for many urologists, there is a wide diversity in rates of erectile function preservation.

Our initial experience with the CaverMap Surgical Aid  has been reported.³ This present study utilized CaverMap in a multi-center single blinded randomized trial intended to determine,

1. whether intra-operative use of this novel device leads to better patient outcome compared to conventional nerve sparing technique. 

2. whether an objective measure of the degree to which nerves have been spared correlates to return of erectile function.

Function was determined both by validated Sexual Function Inventory Questionnaire (SF10) and objective RigiScan evaluations.

Materials and Methods:

Eligibility requirements:  

Patients were randomized intra-operatively to 1) Study arm: Intra-operative nerve stimulation with tumescence monitoring used to identify and spare cavernous nerves during division of the lateral pedicles of the prostate and proximal nerve stimulation following prostatic resection to determine whether efferent stimulation was possible, or 2) Control Arm: Conventional nerve sparing approach with proximal nerve stimulation only at the end of the procedure to determine response. Patients were blinded to their randomization group throughout the follow-up period.

Technique

Stimulation was attempted at the left and right cavernous nerve regions as depicted in Figure 1. In the Study Arm, initial nerve stimulation was performed on each side posteo-lateral to the urethra (baseline) prior to dividing it. If no tumescence response occurred, the stimulation procedure was discontinued. If a tumescence response occurred, each lateral pedicle was stimulated prior to division. If tumescence occurred as a result of stimulation, the tissue at the site of stimulation was spared (without compromising cancer control) and the lateral pedicle 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.

A sample graph of a radical prostatectomy stimulation and response when using CaverMap™ is shown (Figure 2). A minimum change in tumescence of 0.5% was considered a tumescence response. This response reflected the minimal detectable increase in penile girth in response to nerve stimulation, indicating neural continuity between the area of stimulation and the erectile bodies.

Results:

• 61 patients at 6 institutions
• Age 39 to 70 years (mean 60.5)
• Eight not evaluable due to absence of post-prostate removal proximal stimulation data (5) or device failure (3).
• Bilateral nerve sparing was attempted in 45 of 53 patients. Unilateral nerve sparing was attempted for B patients.
• Patients who followed a course of radiation or hormonal therapy following surgery were excluded from the evaluation at 12 months, leaving 45 patients evaluable.

 Intraoperative Results:

lntraoperative results presented at the 1998 AUA meeting demonstrated that when bilateral nerve sparing  was attempted, nerves were successfully spared bilaterally in 73% of study patients compared to only 56% of control patients. This difference did not reach statistical significance.

12 month results:

Return Of Erectile Function Measured At 12 Months Post Surgery vs. CaverMap™ Surgical Response At End Of Surgery (Bilateral, Unilateral, no response)

There is a significant correlation between CaverMap™ prediction of nerve function and return of erectile function at 12 months post surgery (based upon patient questionnaire) and a high correlation with results of RigiScan testing.

There was a significant improvement in patient outcome in the CaverMap™ group as measured by RigiScan.

Other data:

Mean operative time increased by 23 minutes in the study group; this difference did not achieve significance. Median blood loss was 950 cc in the control group and 1245 cc in the study group, possibly reflecting the increase in OR time. There was no difference in transfusion requirements or the rate of positive margins.

Conclusions:

• A randomized study can be conducted with radical prostatectomy patients to evaluate differences in outcome related to surgical methodology obectively.
• Use of intra-operative cavernous nerve stimulation with tumescence monitoring permits rapid identification of the course of the cavernous nerves during radical prostatectomy.
• Rates of margin positivity were not significantly different when CaverMapTM was used intraoperatively.
• Use of the device increases operative time by about 20 minutes.
• Blood loss was not significantly different between the 2 arms.
• A tumescence response immediately following removal of the prostate accurately predicted return of erectile function.
• lntraoperative use of CaverMap led to improved erectile function with no associated adverse events.

Reference:

1. AUA Prostate Cancer Clinical Guidelines Panel Report on the Management of clinically localized prostate cancer. Published by AUA, 1995 Pg. A-20

2. Zippe CD, Kedia AW, Kedia K, Nelson DR, Agarwal A. Treatment of erectile dysfunction after radical prostatectomy with sildenefil citrate. Urology 1998 52(6), 963-6

3. Klotz LH, Herschom SH. Early experience with intraoperative cavornous nerve stimulation with penile tumescence monitoring. Urology 52:537-542, 1998.