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A positive caver map response poorly predicts recovery of potency after radical prostatectomy
RAPID COMMUNICATION
A POSITIVE CaverMap RESPONSE POORLY PREDICTS RECOVERY OF POTENCY AFTER RADICAL PROSTATECTOMY HYUNG L. KIM, DAVID S. STOFFEL, DEBORAH A. MHOON,
AND
CHARLES B. BRENDLER
ABSTRACT Objectives. To determine whether preservation of the neurovascular bundles (NVBs), defined by a positive CaverMap response, correlates with the recovery of potency after radical prostatectomy. Methods. We studied a group of 60 men who were potent preoperatively who underwent radical retropubic prostatectomy by one surgeon. The CaverMap was used after removal of the prostate to assess the integrity of the NVBs. Postoperative potency was assessed by a postal questionnaire and telephone interview, administered independently of the treating surgeon. Men were considered potent if they reported postoperative erections consistently sufficient for vaginal penetration with or without the use of sildenafil. Results. The mean patient age was 59 years, and the median follow-up was 365 days. A positive CaverMap response was obtained in 73 (77%) of the 95 NVBs tested. The overall potency rate was 18%. No patients with a bilateral negative CaverMap response were potent, and 2 (22%) of 9 with a unilateral CaverMap response (negative versus unilateral response, P ⫽ 0.46) and 6 (27%) of 22 with bilateral CaverMap responses (negative versus bilateral response, P ⫽ 0.32) were potent. Conclusions. A positive CaverMap response, suggesting that a successful nerve-sparing prostatectomy had been performed, was obtained in 77% of the NVBs tested. Nevertheless, with a median follow-up of 12 months, most patients with a positive CaverMap response remained impotent. This suggests that other factors are critical to the recovery of sexual function after radical prostatectomy. UROLOGY 56: 561–564, 2000. © 2000, Elsevier Science Inc.
D
espite improvements in surgical technique to preserve sexual function, impotence remains a frequent complication after radical prostatectomy. Although excellent potency results have been reported from several institutions, other institutions have reported far less favorable results (Table I).1 This wide disparity may be due to multiple factors, including patient selection, surgical technique, and differences in data collection methods. The CaverMap Surgical Aid (Uromed, Boston, Mass) is a device designed to assess the functional integrity of the neurovascular bundles (NVBs) during radical prostatectomy. The instrument consists of a hand-held wand with eight electrodes at the tip that are positioned over the NVBs to deliver a set electrical current. A strain gauge placed around the From the Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois Reprint requests: Hyung Kim, M.D., Section of Urology/ MC6038, University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, Chicago, IL 60637 Submitted: May 31, 2000, accepted (with revisions): June 19, 2000 © 2000, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
penile shaft measures changes in the circumference of the penis after stimulation of the NVBs with the CaverMap. In this study, we used the CaverMap to determine the integrity of the NVBs after removal of the prostate and correlated these results with the recovery of potency postoperatively. MATERIAL AND METHODS Between May 1998 and April 1999, the CaverMap device was used during 60 radical retropubic prostatectomies performed by one surgeon (C.B.B.) who has performed more than 1700 such procedures for localized prostate cancer. The CaverMap device was used in all radical prostatectomies performed during this time, except when nerve sparing was not attempted or when the CaverMap was unavailable. Patients who reported reduced or absent erectile function preoperatively were excluded from the study. The criteria for sacrificing the NVBs included (a) ipsilateral Gleason grade 7 or greater or three or more involved cores from one lobe on the preoperative needle biopsy, (b) palpable tumor, particularly at the apex, encroaching on the NVB, and (c) adherence of the prostate to either the lateral pelvic fascia or the NVB. All operations were performed using previously reported modifications2 to the anatomic approach originally described by Walsh and Donker.3 With the CaverMap positioned over the midregion of the 0090-4295/00/$20.00 PII S0090-4295(00)00748-2 561
TABLE I. Representative potency rates after radical retropubic prostatectomy Potency Rates (%)
Study Jonler et al., 1994 Pedersen et al., 1993 Ritchie et al., 1989 Leandri et al., 1992 Catalona et al., 1993 Drago et al., 1992 Quinlan et al., 1991
11 19 12 56 59 66 68
Data from Robinson et al.1
prostate bed, the NVBs were assessed after the prostate and seminal vesicles had been removed and immediately before performing the vesicourethral anastomosis. As initially recommended by the manufacturer, the CaverMap was used to deliver a sequentially increasing current of 16 to 20 mA to the NVBs. A positive response was defined by tumescence or detumescence, resulting in a change in circumference of 1% or more at the base of the penile shaft. As a negative control, the current was delivered to areas away from the NVBs (eg, rectum, bladder, and pelvic floor) to confirm the absence of an erectile response.
STAGING The clinical stage was determined by digital rectal examination. A prostate-specific antigen level was obtained in all patients preoperatively. A bone scan and pelvic computed tomography scan were performed to exclude metastatic disease when indicated. Pathologic stage was determined as previously described.2 The clinical and pathologic stage were classified according to the TNM system.
FOLLOW-UP Potency was assessed with a mailed questionnaire designed and administered independently of the treating surgeon. The questionnaires were mailed at 6 months and again at a median follow-up of 365 days. Additional follow-up was obtained when necessary by a telephone interview, which was conducted by a clinical nurse or urology resident. The questionnaire was developed using relevant items from the University of California, Los Angeles, Prostate Cancer Index.4 Patients were considered potent if they reported erections sufficient for vaginal penetration at least 50% of the time intercourse was attempted. Patients were also considered potent if they were able to achieve erections with the assistance of sildenafil but were considered impotent if they required other treatments such as vacuum pumps or topical or injectable alprostadil to achieve adequate erections.
STATISTICAL ANALYSIS A software package, Minitab Release 12, was used to perform the statistical analysis. Tabulated statistical analysis and Fisher’s exact test were used to compare the proportion of men who were potent versus those who were impotent postoperatively, categorized by the intraoperative CaverMap response.
RESULTS The patient demographic data are summarized in Table II. The mean age was 59 years, and the median follow-up was 365 days. All patients had been 562
TABLE II. Patient characteristics Mean age (yr) Race (n) White Black Other Mean preoperative PSA (ng/mL) Clinical stage (n) T1a T1c T2 Mean intraoperative EBL (mL) Anesthesia (n) General Epidural and/or spinal Attempted nerve sparing (n) Unilateral Bilateral Pathologic stage (n) pT2 pT3a or pT3b pT3c or N⫹ Pathologic Gleason score (n) 5 or 6 7 8 Positive surgical margin
58 ⫾ 6.8 55 3 2 6.9 1 41 18 1058
(92) (5) (3) ⫾ 4.1 (2) (68) (30) ⫾ 406
18 (30) 42 (70) 25 (42) 35 (58) 50 (83) 7 (12) 3 (5) 35 24 1 4
(58) (40) (2) (7)
KEY: PSA ⫽ prostate-specific antigen; EBL ⫽ estimated blood loss per anesthesia record. Numbers in parentheses are percentages; data presented as the mean ⫾ SD, unless otherwise noted.
followed for at least 6 months. During surgery, unilateral preservation of the NVBs was attempted in 25 patients. In this group, 20 (80%) of the 25 had a positive CaverMap response. Bilateral preservation of the NVBs was attempted in 35 patients. In this second group, 9 (26%) of the 35 had a positive CaverMap response on one side and 22 (63%) of the 35 had a positive CaverMap response on both sides. Overall, a positive CaverMap response was obtained in 73 (77%) of the 95 NVBs tested. Initially, when a 0.5% change in penile circumference was used as the cutoff for a positive response, some false-positive responses were seen when areas away from the NVBs were stimulated. However, using a 1% change as the cutoff for a positive response, no false-positive responses occurred. At a median of 365 days postoperatively, only 11 (18%) of 60 men reported regaining potency. In this group, 5 of 11 were using sildenafil to enhance their erections. The median follow-up for the subgroup of men potent postoperatively was 380 days. Although no patient with a negative CaverMap response regained potency, a unilateral or bilateral CaverMap response by no means guaranteed recovery of potency postoperatively (Table III). With attempted preservation of one NVB, 0 of 5 patients with a negative CaverMap response and 3 (15%) of UROLOGY 56 (4), 2000
TABLE III. CaverMap response vs. postoperative potency after radical prostatectomy CaverMap Response After Attempted Preservation of 1 NVB*
Not potent (n) Potent (n)
CaverMap Response After Attempted Preservation of 2 NVBs†
Negative
Positive
Negative
Positiveunilateral
Positivebilateral
5 (100) 0
17 (85) 3 (15)
4 (100) 0
7 (78) 2 (22)
16 (73) 6 (27)
KEY: NVB ⫽ neurovascular bundle. * P ⫽ 0.50. † P ⫽ 0.46 (negatiave vs. unilateral CaverMap response) or P ⫽ 0.32 (negative vs. bilateral CaverMap response).
20 patients with a positive CaverMap response were potent (P ⫽ 0.50). With attempted preservation of both NVBs, 0 of 4 patients with a negative CaverMap response, 2 (22%) of 9 with a unilateral CaverMap response (negative versus unilateral response, P ⫽ 0.46), and 6 (27%) of 22 patients with a bilateral CaverMap response (negative versus bilateral response, P ⫽ 0.32) were potent. When patients with a negative CaverMap response were compared with all men with any intraoperative CaverMap response (unilateral or bilateral), the difference in potency did not reach statistical significance (P ⫽ 0.123). COMMENT It is well established that the cavernous nerves can be stimulated in vivo to produce at least partial and sometimes full erections in both animals and humans.5,6 Using the CaverMap device, stimulation of the NVBs can be detected by measuring the changes in penile circumference. A 1% change in penile circumference was used to define a positive response. Using this definition for a positive response, no false-positive responses were obtained when areas away from the NVBs were stimulated. During 60 consecutive radical prostatectomies in which NVB preservation was attempted and the CaverMap used, 73 (77%) of 95 NVB units were preserved. With a median follow-up of 365 days, however, only 18% of these men reported regaining sufficient potency for sexual intercourse. In our study, recovery of potency did not correlate with the intraoperative CaverMap response. This is in contrast to a preliminary report by Klotz et al.7 of approximately 30 men, 6 months after prostatectomy. A positive CaverMap response on neither, one, or both sides, after removal of the prostate gland, was associated with the recovery of erectile function in 0%, 40%, and 83%, respectively (P ⫽ 0.0098). The varied conclusions in these two studies may be due to the relatively short follow-up or the differences in the methods used to assess and define postoperative potency. Klotz and Herschorn8 initially reported that the UROLOGY 56 (4), 2000
CaverMap helped identify the NVBs and guide the nerve-sparing approach in 16 of 17 patients who had a positive CaverMap response. However, in a preliminary report of a randomized Phase III study by the same investigators, CaverMap-assisted prostatectomy did not significantly improve postoperative potency or the RigiScan results compared with conventional nerve-sparing prostatectomy.7 We noted during the course of this study that the surface of the electrode at the tip of the CaverMap was too wide for precise anatomic localization of the NVBs. Furthermore, particularly in older men, the prostate is often enlarged and increased fat may be present in the pelvis, making it difficult to displace the prostate to place the electrodes over the NVBs. The CaverMap was useful, however, in verifying the integrity of the NVBs immediately after the prostate gland and seminal vesicles had been removed and hemostasis achieved. None of the patients who did not have at least a unilateral CaverMap response was potent, suggesting that preservation of the cavernous nerve is required for recovery of potency. However, although our sample size was small and few men were potent after surgery, the lack of a statistically significant correlation between a positive CaverMap response and recovery of erectile function postoperatively underscores the hypothesis that erectile dysfunction after radical prostatectomy is multifactorial. The mechanism of injury after radical retropubic prostatectomy may include damage to the nerves, vessels, and penile corporal tissue. Vascular injury has been implicated. Specifically, the role of the accessory pudendal artery has been studied by others. On the basis of a cadaveric dissection involving a small sample size, the incidence of an accessory pudendal artery has been estimated to be 85%.9 However, studies using pudendal angiography estimate the incidence of an accessory pudendal artery to be only 7% to 21%.10,11 In a report by Polascik and Walsh,12 sacrificing the accessory pudendal artery during prostatectomy did not adversely affect potency. Taken together, these findings suggest a relatively minor role for the ac563
cessory pudendal artery in the recovery of erectile function. After prostatectomy, an ongoing injury contributing to erectile dysfunction may be occurring within the corpora cavernosa of the penis. Ciancio and Kim13 reported that 41% of patients after radical prostatectomy have penile fibrotic changes. Similarly, Klein et al.14 reported that denervation of the rat penis leads to apoptosis of penile erectile tissue. During prostatectomy, it is possible that, despite the ability to produce subtle changes in penile girth when stimulated with the CaverMap, the cavernous nerve is temporarily or partially damaged. Such temporary or partial cavernous nerve injury may lead to apoptosis, atrophy, or fibrosis of the erectile tissues. This possibility is supported by the observation that the parasympathetic fibers of the cavernous nerve are very sensitive to mechanical stress. Using higher currents than used in this study, Michl et al.6 were able to stimulate the cavernous nerve and achieve visible erections at the beginning of the prostatectomy but never at the end. The erectile tissues of the penis may require frequent and periodic neurologic stimulation. This may explain why males have spontaneous nocturnal erections starting in early childhood and also why early intracavernous injection therapy after prostatectomy may improve recovery of erectile function.15 If temporary/partial injury to the NVBs and the lack of neural stimulation to the penis leads to more permanent damage involving the erectile tissue, perhaps intracavernous injection therapy started within the immediate postoperative period can further enhance the recovery of erectile function. CONCLUSIONS Using the CaverMap device to assess the functional integrity of the NVBs, 77% of the NVBs were preserved during attempted nerve-sparing radical prostatectomy. With a median follow-up of 365 days, however, the overall potency rate was only 18%, and recovery of erectile function did not correlate with the intraoperative CaverMap response. Thus, although preservation of the NVBs appears
564
necessary, it does not guarantee recovery of erectile function. We believe, therefore, that erectile dysfunction after radical prostatectomy is probably multifactorial. REFERENCES 1. Robinson JW, Dufour MS, and Fung TS: Erectile functioning of men treated for prostate carcinoma. Cancer 79: 538 –544, 1997. 2. Alsikafi NF, and Brendler CB: Surgical modifications of radical retropubic prostatectomy to decrease incidence of positive surgical margins. J Urol 159: 1281–1285, 1998. 3. Walsh PC, and Donker PJ: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 128: 492– 497, 1982. 4. Litwin MS, Hays RD, Fink A, et al: The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Med Care 36: 1002– 1012, 1998. 5. Lue TF, Schmidt RA, and Tanagho EA: Electrostimulation and penile erection. Urol Int 40: 60 – 64, 1985. 6. Michl U, Dietz R, and Huland H: Is intraoperative electrostimulation of erectile nerves possible? J Urol 162: 1610 – 1613, 1999. 7. 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, 1999. 8. 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. 9. Martinez-Pineiro L, Julve E, and Martinez-Pineiro JA: Topographical anatomy of the penile arteries. Br J Urol 80: 463– 467, 1997. 10. Rosen MP, Greenfield AJ, Walker TG, et al: Arteriogenic impotence: findings in 195 impotent men examined with selective internal pudendal angiography. Radiology 174: 1043–1048, 1990. 11. Gray RR, Keresteci AG, St. Louis EL, et al: Investigation of impotence by internal pudendal angiography: experience with 73 cases. Radiology 144: 773–780, 1982. 12. Polascik TJ, and Walsh PC: Radical retropubic prostatectomy: the influence of accessory pudendal arteries on the recovery of sexual function. J Urol 154: 150 –152, 1995. 13. Ciancio SJ, and Kim ED: Penile fibrotic changes after radical retropubic prostatectomy. BJU Int 85: 101–106, 2000. 14. Klein LT, Miller MI, Buttyan R, et al: Apoptosis in the rat penis after penile denervation. J Urol 158: 626 – 630, 1997. 15. Montorsi F, Guazzoni G, Strambi LF, et al: Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 158: 1408 –1410, 1997.
UROLOGY 56 (4), 2000
A POSITIVE CaverMap RESPONSE POORLY PREDICTS RECOVERY OF POTENCY AFTER RADICAL PROSTATECTOMY HYUNG L. KIM, DAVID S. STOFFEL, DEBORAH A. MHOON,
AND
CHARLES B. BRENDLER
ABSTRACT Objectives. To determine whether preservation of the neurovascular bundles (NVBs), defined by a positive CaverMap response, correlates with the recovery of potency after radical prostatectomy. Methods. We studied a group of 60 men who were potent preoperatively who underwent radical retropubic prostatectomy by one surgeon. The CaverMap was used after removal of the prostate to assess the integrity of the NVBs. Postoperative potency was assessed by a postal questionnaire and telephone interview, administered independently of the treating surgeon. Men were considered potent if they reported postoperative erections consistently sufficient for vaginal penetration with or without the use of sildenafil. Results. The mean patient age was 59 years, and the median follow-up was 365 days. A positive CaverMap response was obtained in 73 (77%) of the 95 NVBs tested. The overall potency rate was 18%. No patients with a bilateral negative CaverMap response were potent, and 2 (22%) of 9 with a unilateral CaverMap response (negative versus unilateral response, P ⫽ 0.46) and 6 (27%) of 22 with bilateral CaverMap responses (negative versus bilateral response, P ⫽ 0.32) were potent. Conclusions. A positive CaverMap response, suggesting that a successful nerve-sparing prostatectomy had been performed, was obtained in 77% of the NVBs tested. Nevertheless, with a median follow-up of 12 months, most patients with a positive CaverMap response remained impotent. This suggests that other factors are critical to the recovery of sexual function after radical prostatectomy. UROLOGY 56: 561–564, 2000. © 2000, Elsevier Science Inc.
D
espite improvements in surgical technique to preserve sexual function, impotence remains a frequent complication after radical prostatectomy. Although excellent potency results have been reported from several institutions, other institutions have reported far less favorable results (Table I).1 This wide disparity may be due to multiple factors, including patient selection, surgical technique, and differences in data collection methods. The CaverMap Surgical Aid (Uromed, Boston, Mass) is a device designed to assess the functional integrity of the neurovascular bundles (NVBs) during radical prostatectomy. The instrument consists of a hand-held wand with eight electrodes at the tip that are positioned over the NVBs to deliver a set electrical current. A strain gauge placed around the From the Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois Reprint requests: Hyung Kim, M.D., Section of Urology/ MC6038, University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, Chicago, IL 60637 Submitted: May 31, 2000, accepted (with revisions): June 19, 2000 © 2000, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
penile shaft measures changes in the circumference of the penis after stimulation of the NVBs with the CaverMap. In this study, we used the CaverMap to determine the integrity of the NVBs after removal of the prostate and correlated these results with the recovery of potency postoperatively. MATERIAL AND METHODS Between May 1998 and April 1999, the CaverMap device was used during 60 radical retropubic prostatectomies performed by one surgeon (C.B.B.) who has performed more than 1700 such procedures for localized prostate cancer. The CaverMap device was used in all radical prostatectomies performed during this time, except when nerve sparing was not attempted or when the CaverMap was unavailable. Patients who reported reduced or absent erectile function preoperatively were excluded from the study. The criteria for sacrificing the NVBs included (a) ipsilateral Gleason grade 7 or greater or three or more involved cores from one lobe on the preoperative needle biopsy, (b) palpable tumor, particularly at the apex, encroaching on the NVB, and (c) adherence of the prostate to either the lateral pelvic fascia or the NVB. All operations were performed using previously reported modifications2 to the anatomic approach originally described by Walsh and Donker.3 With the CaverMap positioned over the midregion of the 0090-4295/00/$20.00 PII S0090-4295(00)00748-2 561
TABLE I. Representative potency rates after radical retropubic prostatectomy Potency Rates (%)
Study Jonler et al., 1994 Pedersen et al., 1993 Ritchie et al., 1989 Leandri et al., 1992 Catalona et al., 1993 Drago et al., 1992 Quinlan et al., 1991
11 19 12 56 59 66 68
Data from Robinson et al.1
prostate bed, the NVBs were assessed after the prostate and seminal vesicles had been removed and immediately before performing the vesicourethral anastomosis. As initially recommended by the manufacturer, the CaverMap was used to deliver a sequentially increasing current of 16 to 20 mA to the NVBs. A positive response was defined by tumescence or detumescence, resulting in a change in circumference of 1% or more at the base of the penile shaft. As a negative control, the current was delivered to areas away from the NVBs (eg, rectum, bladder, and pelvic floor) to confirm the absence of an erectile response.
STAGING The clinical stage was determined by digital rectal examination. A prostate-specific antigen level was obtained in all patients preoperatively. A bone scan and pelvic computed tomography scan were performed to exclude metastatic disease when indicated. Pathologic stage was determined as previously described.2 The clinical and pathologic stage were classified according to the TNM system.
FOLLOW-UP Potency was assessed with a mailed questionnaire designed and administered independently of the treating surgeon. The questionnaires were mailed at 6 months and again at a median follow-up of 365 days. Additional follow-up was obtained when necessary by a telephone interview, which was conducted by a clinical nurse or urology resident. The questionnaire was developed using relevant items from the University of California, Los Angeles, Prostate Cancer Index.4 Patients were considered potent if they reported erections sufficient for vaginal penetration at least 50% of the time intercourse was attempted. Patients were also considered potent if they were able to achieve erections with the assistance of sildenafil but were considered impotent if they required other treatments such as vacuum pumps or topical or injectable alprostadil to achieve adequate erections.
STATISTICAL ANALYSIS A software package, Minitab Release 12, was used to perform the statistical analysis. Tabulated statistical analysis and Fisher’s exact test were used to compare the proportion of men who were potent versus those who were impotent postoperatively, categorized by the intraoperative CaverMap response.
RESULTS The patient demographic data are summarized in Table II. The mean age was 59 years, and the median follow-up was 365 days. All patients had been 562
TABLE II. Patient characteristics Mean age (yr) Race (n) White Black Other Mean preoperative PSA (ng/mL) Clinical stage (n) T1a T1c T2 Mean intraoperative EBL (mL) Anesthesia (n) General Epidural and/or spinal Attempted nerve sparing (n) Unilateral Bilateral Pathologic stage (n) pT2 pT3a or pT3b pT3c or N⫹ Pathologic Gleason score (n) 5 or 6 7 8 Positive surgical margin
58 ⫾ 6.8 55 3 2 6.9 1 41 18 1058
(92) (5) (3) ⫾ 4.1 (2) (68) (30) ⫾ 406
18 (30) 42 (70) 25 (42) 35 (58) 50 (83) 7 (12) 3 (5) 35 24 1 4
(58) (40) (2) (7)
KEY: PSA ⫽ prostate-specific antigen; EBL ⫽ estimated blood loss per anesthesia record. Numbers in parentheses are percentages; data presented as the mean ⫾ SD, unless otherwise noted.
followed for at least 6 months. During surgery, unilateral preservation of the NVBs was attempted in 25 patients. In this group, 20 (80%) of the 25 had a positive CaverMap response. Bilateral preservation of the NVBs was attempted in 35 patients. In this second group, 9 (26%) of the 35 had a positive CaverMap response on one side and 22 (63%) of the 35 had a positive CaverMap response on both sides. Overall, a positive CaverMap response was obtained in 73 (77%) of the 95 NVBs tested. Initially, when a 0.5% change in penile circumference was used as the cutoff for a positive response, some false-positive responses were seen when areas away from the NVBs were stimulated. However, using a 1% change as the cutoff for a positive response, no false-positive responses occurred. At a median of 365 days postoperatively, only 11 (18%) of 60 men reported regaining potency. In this group, 5 of 11 were using sildenafil to enhance their erections. The median follow-up for the subgroup of men potent postoperatively was 380 days. Although no patient with a negative CaverMap response regained potency, a unilateral or bilateral CaverMap response by no means guaranteed recovery of potency postoperatively (Table III). With attempted preservation of one NVB, 0 of 5 patients with a negative CaverMap response and 3 (15%) of UROLOGY 56 (4), 2000
TABLE III. CaverMap response vs. postoperative potency after radical prostatectomy CaverMap Response After Attempted Preservation of 1 NVB*
Not potent (n) Potent (n)
CaverMap Response After Attempted Preservation of 2 NVBs†
Negative
Positive
Negative
Positiveunilateral
Positivebilateral
5 (100) 0
17 (85) 3 (15)
4 (100) 0
7 (78) 2 (22)
16 (73) 6 (27)
KEY: NVB ⫽ neurovascular bundle. * P ⫽ 0.50. † P ⫽ 0.46 (negatiave vs. unilateral CaverMap response) or P ⫽ 0.32 (negative vs. bilateral CaverMap response).
20 patients with a positive CaverMap response were potent (P ⫽ 0.50). With attempted preservation of both NVBs, 0 of 4 patients with a negative CaverMap response, 2 (22%) of 9 with a unilateral CaverMap response (negative versus unilateral response, P ⫽ 0.46), and 6 (27%) of 22 patients with a bilateral CaverMap response (negative versus bilateral response, P ⫽ 0.32) were potent. When patients with a negative CaverMap response were compared with all men with any intraoperative CaverMap response (unilateral or bilateral), the difference in potency did not reach statistical significance (P ⫽ 0.123). COMMENT It is well established that the cavernous nerves can be stimulated in vivo to produce at least partial and sometimes full erections in both animals and humans.5,6 Using the CaverMap device, stimulation of the NVBs can be detected by measuring the changes in penile circumference. A 1% change in penile circumference was used to define a positive response. Using this definition for a positive response, no false-positive responses were obtained when areas away from the NVBs were stimulated. During 60 consecutive radical prostatectomies in which NVB preservation was attempted and the CaverMap used, 73 (77%) of 95 NVB units were preserved. With a median follow-up of 365 days, however, only 18% of these men reported regaining sufficient potency for sexual intercourse. In our study, recovery of potency did not correlate with the intraoperative CaverMap response. This is in contrast to a preliminary report by Klotz et al.7 of approximately 30 men, 6 months after prostatectomy. A positive CaverMap response on neither, one, or both sides, after removal of the prostate gland, was associated with the recovery of erectile function in 0%, 40%, and 83%, respectively (P ⫽ 0.0098). The varied conclusions in these two studies may be due to the relatively short follow-up or the differences in the methods used to assess and define postoperative potency. Klotz and Herschorn8 initially reported that the UROLOGY 56 (4), 2000
CaverMap helped identify the NVBs and guide the nerve-sparing approach in 16 of 17 patients who had a positive CaverMap response. However, in a preliminary report of a randomized Phase III study by the same investigators, CaverMap-assisted prostatectomy did not significantly improve postoperative potency or the RigiScan results compared with conventional nerve-sparing prostatectomy.7 We noted during the course of this study that the surface of the electrode at the tip of the CaverMap was too wide for precise anatomic localization of the NVBs. Furthermore, particularly in older men, the prostate is often enlarged and increased fat may be present in the pelvis, making it difficult to displace the prostate to place the electrodes over the NVBs. The CaverMap was useful, however, in verifying the integrity of the NVBs immediately after the prostate gland and seminal vesicles had been removed and hemostasis achieved. None of the patients who did not have at least a unilateral CaverMap response was potent, suggesting that preservation of the cavernous nerve is required for recovery of potency. However, although our sample size was small and few men were potent after surgery, the lack of a statistically significant correlation between a positive CaverMap response and recovery of erectile function postoperatively underscores the hypothesis that erectile dysfunction after radical prostatectomy is multifactorial. The mechanism of injury after radical retropubic prostatectomy may include damage to the nerves, vessels, and penile corporal tissue. Vascular injury has been implicated. Specifically, the role of the accessory pudendal artery has been studied by others. On the basis of a cadaveric dissection involving a small sample size, the incidence of an accessory pudendal artery has been estimated to be 85%.9 However, studies using pudendal angiography estimate the incidence of an accessory pudendal artery to be only 7% to 21%.10,11 In a report by Polascik and Walsh,12 sacrificing the accessory pudendal artery during prostatectomy did not adversely affect potency. Taken together, these findings suggest a relatively minor role for the ac563
cessory pudendal artery in the recovery of erectile function. After prostatectomy, an ongoing injury contributing to erectile dysfunction may be occurring within the corpora cavernosa of the penis. Ciancio and Kim13 reported that 41% of patients after radical prostatectomy have penile fibrotic changes. Similarly, Klein et al.14 reported that denervation of the rat penis leads to apoptosis of penile erectile tissue. During prostatectomy, it is possible that, despite the ability to produce subtle changes in penile girth when stimulated with the CaverMap, the cavernous nerve is temporarily or partially damaged. Such temporary or partial cavernous nerve injury may lead to apoptosis, atrophy, or fibrosis of the erectile tissues. This possibility is supported by the observation that the parasympathetic fibers of the cavernous nerve are very sensitive to mechanical stress. Using higher currents than used in this study, Michl et al.6 were able to stimulate the cavernous nerve and achieve visible erections at the beginning of the prostatectomy but never at the end. The erectile tissues of the penis may require frequent and periodic neurologic stimulation. This may explain why males have spontaneous nocturnal erections starting in early childhood and also why early intracavernous injection therapy after prostatectomy may improve recovery of erectile function.15 If temporary/partial injury to the NVBs and the lack of neural stimulation to the penis leads to more permanent damage involving the erectile tissue, perhaps intracavernous injection therapy started within the immediate postoperative period can further enhance the recovery of erectile function. CONCLUSIONS Using the CaverMap device to assess the functional integrity of the NVBs, 77% of the NVBs were preserved during attempted nerve-sparing radical prostatectomy. With a median follow-up of 365 days, however, the overall potency rate was only 18%, and recovery of erectile function did not correlate with the intraoperative CaverMap response. Thus, although preservation of the NVBs appears
564
necessary, it does not guarantee recovery of erectile function. We believe, therefore, that erectile dysfunction after radical prostatectomy is probably multifactorial. REFERENCES 1. Robinson JW, Dufour MS, and Fung TS: Erectile functioning of men treated for prostate carcinoma. Cancer 79: 538 –544, 1997. 2. Alsikafi NF, and Brendler CB: Surgical modifications of radical retropubic prostatectomy to decrease incidence of positive surgical margins. J Urol 159: 1281–1285, 1998. 3. Walsh PC, and Donker PJ: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 128: 492– 497, 1982. 4. Litwin MS, Hays RD, Fink A, et al: The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Med Care 36: 1002– 1012, 1998. 5. Lue TF, Schmidt RA, and Tanagho EA: Electrostimulation and penile erection. Urol Int 40: 60 – 64, 1985. 6. Michl U, Dietz R, and Huland H: Is intraoperative electrostimulation of erectile nerves possible? J Urol 162: 1610 – 1613, 1999. 7. 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, 1999. 8. 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. 9. Martinez-Pineiro L, Julve E, and Martinez-Pineiro JA: Topographical anatomy of the penile arteries. Br J Urol 80: 463– 467, 1997. 10. Rosen MP, Greenfield AJ, Walker TG, et al: Arteriogenic impotence: findings in 195 impotent men examined with selective internal pudendal angiography. Radiology 174: 1043–1048, 1990. 11. Gray RR, Keresteci AG, St. Louis EL, et al: Investigation of impotence by internal pudendal angiography: experience with 73 cases. Radiology 144: 773–780, 1982. 12. Polascik TJ, and Walsh PC: Radical retropubic prostatectomy: the influence of accessory pudendal arteries on the recovery of sexual function. J Urol 154: 150 –152, 1995. 13. Ciancio SJ, and Kim ED: Penile fibrotic changes after radical retropubic prostatectomy. BJU Int 85: 101–106, 2000. 14. Klein LT, Miller MI, Buttyan R, et al: Apoptosis in the rat penis after penile denervation. J Urol 158: 626 – 630, 1997. 15. Montorsi F, Guazzoni G, Strambi LF, et al: Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 158: 1408 –1410, 1997.
UROLOGY 56 (4), 2000