The incidence of erectile dysfunction (ED) in men treated for prostate cancer has been reported to be between 20 and 88 %. Despite the use of nerve sparing techniques, ED is still a common adverse effect in patients, especially older men, after radical retropubic prostatectomy. The successful use of autologous nerve grafts in reconstructive surgery has led to the advent of bilateral nerve graft (sural nerve) during radical retropubic prostatectomy to replace the resected cavernous nerves.
However, there is insufficient scientific evidence to demonstrate the value of sural nerve graft in the management of patients with ED following radical prostatectomy. In particular, there are no comparative studies between this approach and standard medical therapy. Early institution of medical therapy, specifically intracorporal injections, after 2 months post-operatively has resulted in a higher incidence of spontaneous return of erections at 1 year. Furthermore, intracorporal injection has been reported to be the most effective approach for treating ED after radical retropubic prostatectomy. Other methods include the use of vacuum erection devices, sildenafil (Viagra), and implantation of a penile prosthesis. Penile prostheses are expensive and require invasive surgery, but satisfaction rates among patients and partners who have used them have been in the range of 85 %, the highest satisfaction rate among all of the treatments of ED.
Further investigation, using prospective, randomized, controlled studies, is needed to ascertain the role of sural nerve graft during radical retropubic prostatectomy in the management of patients who undergo radical prostatectomy for the treatment of localized prostate cancer. In a study that described their preliminary experience with cavernous nerve graft reconstruction using sural nerve grafts with radical prostatectomy or radical cystectomy, Anastasiadis et al (2003) concluded that sural nerve grafts are feasible and safe after radical prostatectomy and cystectomy. However, candidates usually present with high stage disease, high-risk for recurrence and frequent requirement for adjuvant therapy that further compromises erectile function. Randomized studies with more patients and long follow-up periods are necessary in order to define the ideal candidate for nerve graft procedures.
In recent years, researchers have experimented with absorbable collagen matrix tubes (known as Neuragen Nerve Guide) instead of autologous nerve graft materials when performing nerve grafting to reduce the morbidity of ankle numbness as a consequence of harvesting of the sural nerve. It is thought that by securing the proximal and distal cut ends of the neurovascular bundle into the collage matrix tube, complete capture of regrowing axons is more likely to occur than with an autologous sural nerve graft; thus improving the chances of success. The clinical value of this approach needs to be validated by well-designed controlled studies.
Saito et al (2007) examined the effect of an interposition nerve graft on sexual function after radical prostatectomy. This study included 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the 3 groups. In the age-matched analysis, the post-operative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months post-operatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months post-operatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of co-morbidities were different between the UNG and UNS groups. The authors concluded that the difference of the SXF score between the UNG and UNS groups increased with time after 6 months post-operatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.
Secin et al (2007) stated that cavernous nerve graft is an option for men requiring bilateral cavernous nerve resection for cancer control during radical prostatectomy. These investigators determined the success rate and identified determinants of success of bilateral cavernous nerve grafting following resection of the 2 nerves during radical prostatectomy in patients who were potent pre-operatively. These researchers retrospectively reviewed the records of 44 consecutive patients who underwent bilateral nerve grafting from 1999 to 2004. Post-operative erectile function was defined as the achievement of erections satisfactory for intercourse with or without oral medication. They calculated cumulative erectile function recovery rates using Kaplan-Meier curves. The log rank test was used to compare variables affecting erectile function recovery with p < 0.0083 considered significant after adjusting for the number of variables evaluated using the Bonferroni correction. The overall 5-year cumulative recovery of erectile function permitting penetration was 34 % and the rate of consistent penetration was 11 %. None of the analyzed variables was significantly associated with recovery of post-operative erectile function, including patient age (p = 0.3), incomplete bilateral cavernous nerve resection (p = 0.045), sural nerve grafts compared to genito-femoral or ilio-inguinal nerves as donor sites (p = 0.067), post-radiation salvage radical prostatectomy (p = 0.15), neoadjuvant hormone therapy (p = 0.7) and co-morbidities (p = 0.15) or medications (p = 0.4) affecting erectile function. The authors concluded that bilateral cavernous nerve grafts might be beneficial in select patients. A definitive answer awaits the performance of a multi-institutional, randomized, controlled trial.
Fujioka et al (2007) presented their experience of cavernous nerve graft reconstruction to restore potency following radical prostatectomy (RP). A total of 8 patients with prostate cancer who required radical resection involving 1 cavernous nerve had sural nerve grafting, with 2 or 3 sutures using the autologous vein-guide technique, were included in this study. Seven of the 8 patients had spontaneous erectile activity after grafting and 6 of these patients were able to have intercourse. The findings of this study need to be validated by studies with larger sample size and long-term follow-up.
Joffe and Klotz (2007) evaluated the success of erectile function preservation and recovery in a select group of patients with extensive disease unilaterally on biopsy who were candidates for unilateral nerve sparing and contralateral genito-femoral interposition nerve-grafting RP. Because of its low donor site morbidity, the genito-femoral nerve is an appealing donor source for cavernous nerve grafting during RP. Nerve-sparing RP was performed according to the technique of Walsh on 22 patients with prostate cancer. At follow-up, the patients completed an 11-item self-report questionnaire that included the erectile function (EF) domain of the International Index of Erectile Function. The mean patient age was 62 years (range of 48 to 76). The mean follow-up time was 23 months (range of 9 to 37). Of the 22 patients, 3 reported no ED (EF score of 26 to 30), 3 reported mild ED (EF score of 22 to 25), 1 reported moderate ED (EF score of 11 to 16), and 15 reported severe ED (EF score of less than 11). Eight men continued to experience mild chronic thigh or scrotal numbness after the genito-femoral nerve graft procedure. The authors concluded that the benefits of unilateral nerve grafting with the genito-femoral nerve remain uncertain. They stated that a prospective randomized trial is needed before the widespread adoption of unilateral nerve grafting.
Namiki et al (2007) performed a 3-year longitudinal study assessing the impact of unilateral sural nerve graft on recovery of potency and continence following RP. A total of 113 patients undergoing radical retropubic prostatectomy were classified into 3 groups according to the degree of nerve sparing, that is unilateral nerve preservation with contralateral sural nerve graft interposition, bilateral nerve sparing and unilateral nerve sparing. Urinary continence and potency were estimated by the UCLA Prostate Cancer Index questionnaire. Patients in the nerve sparing plus sural nerve graft group were younger than those in the bilateral nerve sparing or unilateral nerve sparing groups. At baseline the unilateral nerve sparing plus sural nerve graft group and the bilateral nerve sparing group reported better sexual function than the unilateral nerve sparing group (62.1 and 61.5 versus 49.9, p < 0.05). The bilateral nerve sparing group showed more rapid recovery than the unilateral nerve sparing plus sural nerve graft group after radical retropubic prostatectomy (p < 0.01). After 24 months there were no significant differences observed between the bilateral nerve sparing and the unilateral nerve sparing plus sural nerve graft group (28.7 versus 32.9). The bilateral nerve sparing group reported a better sexual function score than the unilateral nerve sparing group throughout the postoperative period (p < 0.05). The bilateral nerve sparing group maintained significantly better urinary function at 1 month after radical retropubic prostatectomy than the unilateral nerve sparing plus sural nerve graft group (p < 0.05). After 3 months these groups were almost continent. The unilateral nerve sparing group reported lower urinary function scores during the first year compared to the other groups. The authors concluded that the nerve graft procedure may contribute to the recovery of urinary function as well as sexual function after radical retropubic prostatectomy. They noted that this finding needs to be validated in a randomized trial.
Mikhail et al (2007) reported their experience with sural nerve grafting during robot-assisted laparoscopic radical prostatectomy (RLRP). Patients with pre-operative potency and a minimum of 6 months follow-up were included in this prospective review. A total of 333 patients met these criteria including 22 of the 25 patients who underwent sural nerve grafting. Patients were divided into 5 groups to compare unilateral and bilateral sural nerve cohorts with non-nerve-sparing and unilateral and bilateral nerve-sparing groups. Patients were followed prospectively using health-related quality-of-life questionnaires. Twenty-two patients underwent sural nerve grafting that included 3 bilateral grafts. Mean follow-up was 14 months. There was no statistical difference in patients' ages, body mass index, pre-operative prostate-specific antigen level, blood loss, complications, and positive margin rate. Operative time was statistically longer for both sural graft cohorts when compared with unilateral (without graft) and bilateral nerve sparing cohorts. No significant differences in subjective or objective sexual function, sexual bother, or urinary function were seen with 6 and 12 months follow-up, possibly related to smaller sural cohorts. Graft-related complications include leg pain in 1 patient. The authors concluded that sural nerve grafting during RLRP is technically feasible and safe and offers improved dexterity and visualization deep within the pelvis. However, they stated that a larger randomized cohort of patients will be needed to validate any improved benefits afforded by the robot system.
Zorn and colleagues (2008) assessed the functional, pathological, and oncological outcomes of men who underwent robot-assisted sural-nerve graft (SNG) interposition. Between February 2003 and May 2007, 1,175 consecutive men underwent robot-assisted laparoscopic radical prostatectomy (RLRP). Database analysis identified 27 men who had SNG: 4 bilateral (BL) and 23 unilateral (UL). Sexual function (SF) was prospectively evaluated pre-operatively and at 1, 3, 6, 12, and 24 months post-operatively using validated questionnaires. Positive surgical margins (PSMs), biochemical recurrence (BCR), and potency were evaluated. Compared with RLRP patients without SNG, patients with SNG were younger (57.2 versus 61.8 yrs, p = 0.02), had a higher Gleason score (p = 0.02), and had a higher clinical and pathological stage (p < 0.001 for both). Mean surgical time was significantly longer (349 versus 195 mins, p < 0.001) in patients with SNG. With a mean follow-up of 26.1 months, 11 (47.8 %) patients with UL-SNG and zero men with BL-SNG regained potency. No significant difference in SF was observed between UL nerve sparing and no SNG (56 %) compared with UL nerve sparing with UL-SNG (p = 0.44). Rates of return-to-baseline SF (RTB-SF) at 6, 12, and 24 months were 11 %, 36 % and 45 % for UL-SNG, respectively, which were also comparable to UL nerve sparing only (p > 0.05). No patient (0 %) in the BL-SNG group ever achieved RTB-SF status at any time point. Positive surgical margins were observed in 37 % (10/27) of all patients. Biochemical recurrence occurred in 9 patients (33.3 %), 7 of whom had PSM (78 %); treatment failure occurred within 6 months of surgery, necessitating androgen deprivation therapy. The authors concluded that despite optimism regarding SNG, long-term functional outcomes have been disappointing, particularly for BL nerve interposition. Unilateral sural-nerve graft does not appear to improve outcomes when compared with men with UL nerve preservation. With the greater risk of PSM and BCR in patients who are considered candidates for SNG, newer treatment modalities are needed to cure their disease while preserving SF.
In a phase II clinical trial, Davis et al (2009) examined if UNS RP plus SNG results in a 50 % relative increase in potency at 2 yrs compared to UNS RP alone. Participants were men with localized prostate cancer recommended for UNS RP, less than 66 yrs old, normal baseline erectile function, and willing to participate in early erectile dysfunction (ED) therapy. Patients were followed-up to 2 yrs; they underwent UNS RP and ED therapy starting at 6 wks: oral prostaglandin type-5 (PDE5) inhibitor, vacuum erection device (VED), and intra-cavernosal injection therapy. In the SNG group, a plastic surgeon performed the procedure at the time of RP. Main outcome measure was the ability to have an erection suitable for intercourse with or without a PDE5 inhibitor at 2 yrs. The hypothesis was that SNG would result in a 60 % potency rate compared to 40 % for controls (80 % power, 5 % 2-way significance). The trial planned to enroll 200 patients, but an interim analysis at 107 patients met criteria for futility and the trial was closed. For patients completing the protocol to 2 yrs, potency was recovered in 32 of 45 (71 %) of SNG and 14 of 21 (67 %) of controls (p = 0.777). By intent-to-treat analysis, potency recovered in 32 of 66 (48.5 %) of SNG and 14 of 41 (34 %) of controls (p = 0.271). No differences were seen in time to potency or quality of life scores for ED and urinary function. Limitations included slower-than-expected accrual and poor compliance with ED therapy: less than 65 % for VED and less than 40 % for injections. The authors concluded that the addition of SNG to a UNS RP did not improve potency at 2 yrs following surgery.