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Recoverability of Erectile Function in Post–Radical Cystectomy Patients: Subjective and Objective Evaluations

      Abstract

      Background

      Literature regarding both subjective and objective evaluations of erectile function following radical cystectomy is deficient.

      Objective

      To study the recoverability of erectile function in post–radical cystectomy patients on subjective and objective bases.

      Design, setting, and participants

      Between March 2003 and March 2005, 45 male patients with organ-confined invasive bladder cancer were prospectively enrolled in this study.

      Intervention

      Radical cystectomy and urinary diversion were offered to all patients (21 patients underwent a nerve-sparing [NS] surgical technique, and 24 patients underwent a non–nerve-sparing [NNS] surgical technique).

      Measurements

      Patients were evaluated preoperatively using the International Index of Erectile Function (IIEF) questionnaire and using penile Doppler ultrasound (PDU). Patients were followed up regularly at 2 mo, 6 mo, and 12 mo using the same parameters.

      Results and limitations

      Among patients in the NS group, 17 patients (78.8%) were potent postoperatively: 12 patients (57.8%) with spontaneous complete tumescence and 5 patients (21%) with partial tumescence using phosphodiesterase type 5 inhibitor (PDE5-I) as erectogenic aid; 4 patients needed intracorporeal prostaglandin E1 injections. In contrast, no patients in the NNS group showed spontaneous erection, and they did not improve with sildenafil; all of them needed prostaglandins as an erectogenic aid.
      The comparison between preoperative and postoperative IIEF domains showed that postoperatively the erectile function and overall satisfaction domains deteriorated initially, but in the NS group they gradually improved with time (p < 0.0001). Corresponding PDU findings were comparable in peak systolic velocity during the course of follow-up in both groups. Although the end diastolic velocity was significantly more deteriorated postoperatively than preoperatively in both groups, gradual improvement in patients in the NS group was more evident 12 mo after surgery.

      Conclusion

      The return of erectile function was better in the NS group on subjective and objective bases. The most significant change was in veno-occlusive function, which improved rapidly and progressively in the NS group during 1 yr of follow-up.

      Keywords

      1. Introduction

      Radical cystoprostatectomy is the current standard procedure for locally confined bladder cancer; however, a major drawback of this approach remains the frequently ensuing postoperative erectile dysfunction (ED). This aspect represents a frequent cause of fear and concern for patients and their partners and has a significant impact on the choice of therapy. ED in postcystectomy patients is attributed to the injury to the pelvic nerve plexus, which provides autonomic innervations to the corporae [
      • Walsh P.C.
      • Donker P.J.
      Impotence following radical prostatectomy: insight into etiology and prevention.
      ].
      Recoverability of erectile function (EF) after radical cystoprostatectomy ranged between 14% and 80% [
      • Schlegel P.N.
      • Walsh P.C.
      Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.
      ,
      • Chiang P.H.
      • Wu W.J.
      • Chiang C.P.
      Nerve-sparing radical cystoprostatectomy: 3-year experience.
      ,
      • Miyao N.
      • Adachi H.
      • Sato Y.
      • et al.
      Recovery of sexual function after nerve- sparing radical prostatectomy or cystectomy.
      ,
      • Taniguchi M.
      • Miwa K.
      • Takeuchi T.
      • et al.
      Voiding function and sexual activity in patient following Hautmann neobladder construction.
      ,
      • Martis G.
      • D’Elia G.
      • Diana M.
      • et al.
      Prostatic capsule- and nerve-sparing cystectomy in organ-confined bladder cancer: preliminary results.
      ,
      • Zippe C.D.
      • Raina R.
      • Massanyi E.Z.
      • et al.
      Sexual function after male radical cystectomy in a sexually active population.
      ]. This could be explained by differences in surgeon skill level, surgical technique, or patient selection criteria; however, the methods of evaluation could also cause the results to be misleading. Subjective methods may give false higher success rates [
      • Beckendorf V.
      • Hay M.
      • Rozan R.
      • et al.
      Changes in sexual function after radiotherapy treatment of prostate cancer.
      ,
      • Catalona W.J.
      • Carvalhal G.F.
      • Mager D.E.
      • Smith D.S.
      Potency, continence, and complication rates in 1,870 consecutive radical retropubic prostatectomies.
      ], whereas objective tests may give false lower results [
      • Mulcahy J.J.
      Erectile function after radical prostatectomy.
      ].
      Patients were evaluated subjectively (using the International Index of Erectile Function [IIEF] questionnaire) [
      • Rosen R.C.
      • Riley A.
      • Wagner G.
      • et al.
      The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
      ] and objectively (by penile Doppler ultrasound [PDU]) to alleviate the subjective bias. The aim of this study was to evaluate the recoverability of EF in a group of patients who underwent either nerve-sparing (NS) or non–nerve-sparing (NNS) cystectomy by comparing the preoperative IIEF questionnaire results and PDU results with their postoperative counterparts.
      According to our knowledge, no studies in the literature (in English) have discussed objective and subjective evaluations of both surgical techniques within a short-term follow-up in post–radical cystoprostatectomy patients.

      2. Methods

      This prospective study was performed between March 2003 and March 2005. The study included 45 potent males with organ-confined bladder cancer who were treated with radical cystectomy and urinary diversion. Those patients with tumors at the bladder base or tumors close to bladder neck had frozen section biopsies from the urethra that were negative for cancer before the decision for a neobladder urinary diversion procedure was made. All patients fulfilled the following criteria: patients were preoperatively potent; patients were married; tumors were confined to bladder (clinically T3 or less); urethra and prostate were free of carcinoma; urethra and prostate were free of neurological and penile diseases; and patients’ ages were between 30 yr and 60 yr.
      The NS technique was applied to a group of 21 patients according to Schlegel and Walsh's [
      • Schlegel P.N.
      • Walsh P.C.
      Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.
      ] modifications of the standard technique that entails meticulous dissection of the anterior prostate and lateral aspect of the prostate-urethral junction with careful retrograde dissection of the posterior aspect from the rectum. In a group of 24 patients a NS technique could not be applied (NNS group) for several reasons: surgeon's judgment, bulky mass, basal tumor or tumor near the bladder neck, pelvic adhesions, or other intraoperative complications hindering the possibility of preventing dissection of the neurovascular bundle.
      Basal preoperative EF was assessed by both IIEF questionnaire [
      • Rosen R.C.
      • Riley A.
      • Wagner G.
      • et al.
      The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
      ] and PDU. The degree of erection was assessed on the basis of the EF domain (the score of six questions regarding EF) of IIEF questionnaire and classified as mild ED (score 17–25), moderate ED (score 11–16), or severe dysfunction (score <10); patients with score >26 were not considered to suffer from ED [
      • Rosen R.C.
      • Riley A.
      • Wagner G.
      • et al.
      The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
      ].
      After the first month, EF was assessed provisionally: complete recovery of spontaneous erectile function, mild tumescence unsatisfactory to intercourse, or complete loss of erectile function. The latter two groups were given phosphodiesterase type 5 inhibitor (PDE5-I; sildenafil citrate, 50 mg) on demand, to be increased to 100 mg after a failed 50-mg response. A total of eight doses were tried before PDE5-I was considered to have failed and a shift to intracorporeal injection (ICI) of prostaglandin E1 (PGE1; 20 mcg) was made.
      The PDU (Toshiba color duplex ultrasound equipment, model SSA-270 A; linear transducer at 7.5 MHz) was connected to a multiformate camera and used to take films that were printed with a Sony video printer (color and black-and-white) using the technique of Zorgnittoi and Lefleur [
      • Zorgniotti A.W.
      • Lefleur R.S.
      Autoinjection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence.
      ]. PDU results were obtained 5 min, 10 min, and 15 min after intracavernosal injection; the peak systolic velocity (PSV) was assessed as follows: >25 cm/s was considered to be normal, 20–25 cm/s was considered to be mild erectile dysfunction, 12–20 cm/s was considered to be moderate erectile dysfunction, and <12 cm/s was considered to be severe arteriogenic impotence [
      • Schwartz A.N.
      Radiographic diagnosis and treatment of erectile dysfunction.
      ]. The end diastolic velocity (EDV) was assessed as follows: ≤5 cm/s was considered to be a normal value, and >5 cm/s was considered to indicate a veno-occlusive disorder [
      • Knispel H.H.
      • Andresen R.
      Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls.
      ]. The patients were followed up regularly at 2 mo, 6 mo, and 12 mo using the same evaluation methods.
      The data was processed using SPSS 11.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical analysis of continuous-variable means were performed using student t tests (paired and unpaired, when appropriate). Analysis of variance (ANOVA) was performed using Chi-square test. A p value of <0.05 was considered statistically significant. Repeated ANOVA tests were applied to identify the significance of the effect of time on both surgical groups and on each group (NS and NNS) separately.

      3. Results

      The 21 patients in the NS group had a mean age of 48.4 yr (range: 31–54 yr), whereas the 24 patients in the NNS group had a mean age of 52.5 yr (range: 45–64 yr; p = 0.14). The preoperative comorbidity parameters of both groups were comparable with no statistical significance (Table 1). No patients had neurological or peripheral vascular diseases; all patients had normal renal and liver functions. Furthermore, both groups did not receive preoperative chemotherapy, radiotherapy, or psychotropic drugs.
      Table 1Preoperative parameters in 45 patients with invasive bladder cancer
      Preoperative parametersNS (n = 21)NNS (n = 24)p
      No. (%)No. (%)
      Smoking13 (61.9)11 (45.8)0.432
      Hypertension3 (14.2)4 (16.6)0.246
      Diabetes mellitus2 (9.5)5 (20.8)0.363
      Preoperative related surgery3 (14.2)8 (33.3)0.060
      Age31–54 yr (mean 48.4 yr)45–64 yr (mean 52.5 yr)0.140
      Abbreviations: NS, nerve-sparing; NNS, non–nerve-sparing.
      Table 2 summarizes the histopathologic features of both groups. Both groups were comparable in histopathologic features and surgical parameters (p > 0.05).
      Table 2Patients and tumor characteristics
      ParametersTotal (n = 45)NS (n = 21)NNS (n = 24)p
      Tumor stage (pathological)pT16330.419
      pT2a413
      pT2b1165
      pT3a1899
      pT3b624
      Nodal staging (pathological)pN03919200.422
      pN1624
      Gross pictureSolid tumors3515200.615
      Papillary1064
      Relation to bladder neckBody of bladder2713140.819
      Base of bladder18810
      Diversion typeOrthotopic3717200.058
      Continent cutaneous541
      Ileal loop33
      Abbreviations: NS, nerve-sparing; NNS, non–nerve-sparing.
      Nerve sparing was not performed in 24 patients (the NNS group) for several reasons: 8 patients had had previous pelvic surgery and had extensive pelvic adhesions, 6 patients presented technical difficulties (4 patients had bulky tumors and 2 patients had bleeding dorsal-vein complications), and 10 patients had a tumor at the bladder base or tumors close to the bladder neck.
      The urinary diversion was orthotopic (ileal neobladder urinary diversion) in 37 patients (82.2%: 17 patients in the NS group and 20 patients in the NNS group), whereas continent cutaneous diversion was used in 5 patients (11.2%: 4 patients in the NS group and 1 patient in the NNS group) in view of short mesentery, and an ileal-loop conduit (Bricker's technique) was used in 3 patients (6.6%) in the NNS group. Regarding oncologic outcomes, there was no recurrence among the patients in this study within the mean oncologic follow-up period of 16.4 mo (range: 12–24 mo).
      Among patients in the NS group, 17 patients (78.8%) were potent postoperatively; 12 patients (57.8%) had spontaneous complete tumescence (mean of EF domain Of IIEF was 25), and 5 patients (21%) had partial tumescence using PDE-5 as an erectogenic aid (the mean of the EF domain was 15). Four patients needed intracorporeal PGE1 injection (the mean of the EF domain was 8). In contrast, no patients in the NNS group showed spontaneous erection. Furthermore, all patients in the NNS group failed to respond to sildenafil therapy, and they required intracorporeal PGE1 injection as an erectogenic aid (the mean of the EF domain was 7).
      The preoperative IIEF domains (EF, orgasm, desire, intercourse satisfaction, and overall satisfaction) were assessed. A control group of healthy, age-matched males were compared to preoperative scoring, and there was no statistical significance (p > 0.05; Table 3). The postoperative scoring of both groups were compared. At follow-up, significant improvement in the EF domain (p = 0.009), the intercourse satisfaction domain (p = 0.02), and the overall satisfaction domain (p = 0.03) were shown, compared with other domains in the NS group (Fig. 1 and Table 4). On the other hand, during the course of follow-up, patients in the NNS group showed a deterioration in all domains compared with preoperative values. Table 3, Table 4 show the comparison between both groups for different IIEF domains.
      Table 3Comparison between the nerve-sparing (NS) cystectomy group and the non–nerve-sparing (NNS) cystectomy group regarding scores from respective domains of International Index of Erectile Function (IIEF) questionnaire
      NS (mean)NNS (mean)p
      Erectile functionControl group (mean ± SD)25.8 ± 7.6
      Preoperative26–28 (25)25–30 (24.9)0.009
      2 mo0–19 (8.8)0–12 (4.7)
      6 mo6–23 (16.4)1–14 (8.4)
      12 mo9–22 (20.2)2–16 (10.5)
      OrgasmControl group (mean ± SD)8.8 ± 2.9
      Preoperative7–11 (8.4)5–10 (8.3)0.118
      2 mo2–6 (3.5)0–7 (1.7)
      6 mo2–6 (3.5)1–7 (3.3)
      12 mo2–8 (4.2)2–7 (3.8)
      DesireControl group (mean ± SD)7.0 ± 1.8
      Preoperative7–9 (8.2)6–10 (8.2)0.703
      2 mo0–9 (6.3)2–6 (3.9)
      6 mo2–7 (4.9)2–9 (4.9)
      12 mo3–7 (5.7)2–9 (5.2)
      Intercourse satisfactionControl group (mean ± SD)10.6 ± 3.9
      Preoperative8–14 (11.1)8–15 (11.6)0.02
      2 mo0–7 (3.4)0–5 (2.09)
      6 mo3–8 (5.5)3–7 (4.3)
      12 mo3–8 (6.3)2–8 (5.4)
      Overall satisfactionControl group (mean ± SD)8.6 ± 1.7
      Preoperative7–10 (8.7)6–10 (8.7)0.03
      2 mo2–6 (3.5)2–6 (2.5)
      6 mo2–8 (4.6)2–6 (3.3)
      12 mo3–8 (5.7)2–7 (4.2)
      Abbreviation: SD, standard deviation.
      Figure thumbnail gr1
      Fig. 1Comparison between surgical groups showing significance of the International Index of Erectile Function (IIEF) questionnaire domains after 12 mo (p < 0.05).
      Table 4Significance (p values) of the International Index of Erectile Function (IIEF) questionnaire domains for nerve-sparing and non–nerve-sparing surgical techniques
      DomainsErectile functionOrgasmDesireSatisfactionOverall
      Effect of
       Time0.00010.00010.00010.00010.0001
       Group0.0090.1180.7030.01720.029
       Group by time0.00010.0050.00010.00010.0001
      Interestingly, the corresponding PDU showed that the PSV deterioration was insignificant during the course of follow-up in both groups (p = 0.79). However, the most significant changes were in EDV, which started to increase in both groups soon after surgery, then significantly improved in the NS group by the end of 12 mo in comparison to preoperative values (p < 0.05; Fig. 2). Fig. 3, Fig. 4, Fig. 5 show examples of preoperative and postoperative PDU pictures. Table 5 presents the PDU findings.
      Figure thumbnail gr2
      Fig. 2Comparison between both surgical groups regarding penile Doppler ultrasound (PDU) at peak systolic velocity (PSV; cm/s) and end diastolic velocity (EDV; cm/s) preoperatively and at month 12 (EDV: p < 0.05; PSV: p > 0.05).
      Figure thumbnail gr3
      Fig. 3Penile Doppler ultrasound (PDU) before surgery (peak systolic velocity [PSV] >35 cm/s and end diastolic velocity [EDV] <5 cm/s or even reversed).
      Figure thumbnail gr4
      Fig. 4Postoperative penile Doppler ultrasound (PDU) in the non–nerve-sparing (NNS) group (at month 12; peak systolic velocity [PSV]: 45.2 cm/s; end diastolic velocity [EDV]: 14.1 cm/s).
      Figure thumbnail gr5
      Fig. 5Postoperative penile Doppler ultrasound (PDU) in nerve-sparing (NS) group (at month 12; peak systolic velocity [PSV]: 57.1 cm/s and end diastolic velocity [EDV]: 2.9 cm/s).
      Table 5Comparison between the nerve-sparing (NS) cystectomy group and the non–nerve-sparing (NNS) cystectomy group regarding penile Doppler ultrasound (PDU)
      NS range (mean ± SD; cm/s)NNS range (mean ± SD; cm/s)p
      Peak systolic velocity030–71 (48 ± 11.7)29–76 (50.1 ± 13.4)0.79
      2 mo41–81 (56.15 ± 11.3)18–77 (52.8 ± 16.7)
      6 mo13–70 (48 ± 17.6)28–75 (52.1 ± 12.8)
      12 mo34–71 (49.3 ± 9.1)35–70 (53.6 ± 10.26)
      End diastolic velocity00–7 (3.2 ± 3.13)0.8–6.7 (2.9 ± 1.49)0.01
      2 mo4.6–17 (10.1 ± 4.3)5–24 (12.7 ± 5.7)
      6 mo0–20 (7.7 ± 4.2)2.5–22 (11 ± 5.4)
      12 mo2.7–10 (5.95 ± 3.8)2–23 (11.1 ± 6.5)
      The comparison of the two methods of evaluation that were used in this study is shown in Table 6. The comparison was carried out between the EF domain of IIEF and the EDV of PDU because both of them showed significant changes during follow-up.
      Table 6Comparison between the methods of evaluation (International Index of Erectile Function [IIEF] questionnaire and penile Doppler ultrasound [PDU])
      IIEF (EF domain score)PDU (EDV value)p
      At 2 mo
       Normal070.14
       Mild ED54
       Moderate ED75
       Severe ED3329
      Total number of cases4545
      At 6 mo
       Normal090.0082
       Mild ED73
       Moderate ED133
       Severe ED2530
      Total number of cases4545
      At 12 mo
       Normal0130.014
       Mild ED73
       Moderate ED216
       Severe ED1723
      Total number of cases4545
      Abbreviations: EF, erectile function; EDV, end diastolic velocity; ED, erectile dysfunction.

      4. Discussion

      Erectile dysfunction (ED) is a common complication in all patients treated by radical cystectomy. In 1982, Walsh and Donker [
      • Walsh P.C.
      • Donker P.J.
      Impotence following radical prostatectomy: insight into etiology and prevention.
      ] suggested that ED was produced by injury to the pelvic nerve plexus, which provides autonomic innervation to the corpora cavernosa. On the basis of these observations, the operative procedures of radical prostatectomy [
      • Walsh P.C.
      • Donker P.J.
      Impotence following radical prostatectomy: insight into etiology and prevention.
      ] and radical cystoprostatectomy [
      • Schlegel P.N.
      • Walsh P.C.
      Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.
      ] were modified to avoid injury to the cavernosal nerves and, thus, preserve potency in most patients undergoing these operations.
      NS pelvic surgeries are often criticized because of the possibility of local failure [
      • Pritchett T.R.
      • Schiff W.M.
      • Klatt E.
      • et al.
      The potency-sparing radical cystectomy: does it compromise the completeness of the cancer resection?.
      ]. Concerns have also been raised that the NS technique may “spare cancer.” However, Brendler demonstrated that the 5-yr disease-specific survival rates and overall survival rates of 65–70% are similar to those associated with a standard radical cystoprostatectomy [
      • Brendler C.B.
      • Steinberg G.D.
      • Marshall F.F.
      • et al.
      Local recurrence and survival following nerve-sparing radical cystoprostatectomy.
      ]. Also, the 5-yr actuarial local recurrence rate of 7.5% suggests that the technique does not compromise cancer control. Schoenberg et al demonstrated that following NS radical cystoprostatectomy for organ-confined cancer, the disease-specific 10-yr survival rate for all stages treated was 69%, and the 10-yr survival rate and freedom from local recurrence was 94% [
      • Schoenberg M.P.
      • Walsh P.C.
      • Breazeale D.R.
      • et al.
      Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-yr follow-up.
      ]. Although this study included a limited number of patients (21 patients in the NS group) and did not have a long-term follow-up, these results may indicate that this type of surgical procedure is safe and satisfactory in terms of local recurrence control because there was no recurrence among these patients within the mean oncologic follow-up time of 16.4 mo (range: 12–24 mo).
      Various potency rates after NS radical cystoprostatectomy have been reported and have shown satisfactory results [
      • Schlegel P.N.
      • Walsh P.C.
      Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.
      ,
      • Chiang P.H.
      • Wu W.J.
      • Chiang C.P.
      Nerve-sparing radical cystoprostatectomy: 3-year experience.
      ,
      • Miyao N.
      • Adachi H.
      • Sato Y.
      • et al.
      Recovery of sexual function after nerve- sparing radical prostatectomy or cystectomy.
      ,
      • Taniguchi M.
      • Miwa K.
      • Takeuchi T.
      • et al.
      Voiding function and sexual activity in patient following Hautmann neobladder construction.
      ,
      • Martis G.
      • D’Elia G.
      • Diana M.
      • et al.
      Prostatic capsule- and nerve-sparing cystectomy in organ-confined bladder cancer: preliminary results.
      ], indicating that 49–80% of patients had erection after NS radical cystoprostatectomy. However, Zippe et al [
      • Zippe C.D.
      • Raina R.
      • Massanyi E.Z.
      • et al.
      Sexual function after male radical cystectomy in a sexually active population.
      ] reported a 37.5% crude rate of potency (6/16) in the NS category, but they reported an overall potency rate of 14% independent of whether the bundles had been preserved. Schoenberg et al [
      • Schoenberg M.P.
      • Walsh P.C.
      • Breazeale D.R.
      • et al.
      Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-yr follow-up.
      ] demonstrated that recovery of sexual function was age-dependent: 62% in patients younger than 50 yr, 47% in patients between 50 yr and 60 yr, and 20% in patients older than 60 yr.
      The variance in the results presented in the literature regarding the preservation of erectile function could be explained by differences in skills, differences in surgical techniques, and differences in patient-selection criteria among studies. The results may also be influenced by the method of evaluating EF. Authors who evaluated EF using a questionnaire before surgery reported a relatively high potency rate [
      • Beckendorf V.
      • Hay M.
      • Rozan R.
      • et al.
      Changes in sexual function after radiotherapy treatment of prostate cancer.
      ,
      • Catalona W.J.
      • Carvalhal G.F.
      • Mager D.E.
      • Smith D.S.
      Potency, continence, and complication rates in 1,870 consecutive radical retropubic prostatectomies.
      ], whereas those who assessed EF with objective tests did not [
      • Mulcahy J.J.
      Erectile function after radical prostatectomy.
      ]. Therefore, we evaluated our patients subjectively (using the IIEF questionnaire) and objectively (using PDU) to alleviate the subjective bias.
      Table 1 shows the differences between the NS group and NNS group with regard to smoking, age at surgery, previous operations, and diabetes, even though they were not significant for the low number of patients in the two groups. This might be due to careful selection of patients. In spite of a low number of patients in this study, there is no statistical difference shown.
      The IIEF questionnaire is an applicable, previously tested, and amenable subjective tool for patients. Moreover, it assesses five domains that are of great value. In spite of this, the questionnaire may be influenced by some preoperative factors, for example, depression after clinical diagnosis or surgical decision or presence of hematuria that might compromise patient mood and libido. Postoperative factors such as postoperative stress and diversion type may also play a role. To overcome this, patients were asked 1 wk or 2 wk before surgery about their sexual behavior 1 mo before the diagnosis, and they were also questioned again 2 mo after hospital discharge.
      Our results show that there is significant progressive increase in EF, intercourse satisfaction, and overall satisfaction domains relative to the basal preoperative level during the follow-up period in the NS group. In contrast, the NNS group showed progressive deterioration.
      From an objective point of view, PDU does not give reference to erectile response, but only to vascular parameters. Nightly erectile function measurements (nocturnal penile tumescence test [NPT]), vibration-provoked, or video-provoked EF measurement should be performed. However, we selected the PDU for objective assessment because it gives more data about the underlying vascular causes of ED, and the etiology of post–radical cysto-prostatectomy ED attributed to veno-occlusive disease requires PDU for assessment.
      PDU did not show significant deterioration of the arterial mechanism postoperatively over preoperative evaluations in both surgical groups (p > 0.05). This may indicate that radical cystoprostatectomy did not compromise the penile arterial inflow, in this group of patients, at least. On the other hand, a significant change was observed in the veno-occlusive mechanism. EDV had deteriorated rapidly and to a significant degree in the NNS group by month 12 (p < 0.001) but had not in the NS group. Those PDU findings correlate with the results of other reports on radical prostatectomy [
      • Penson D.F.
      • Feng Z.
      • Kuniyuki A.
      • et al.
      General quality of life 2 years following treatment for prostate cancer: what influences outcomes? Results from prostate cancer outcome study.
      ,
      • Leungwattanakij S.
      • Bivalacqua T.J.
      • Usta M.F.
      • et al.
      Cavernous neurotomy causes hypoxia and fibrosis in rats corpus cavernosum.
      ].
      In our study spontaneous erection was delayed in the NS group, but did progressively return over the following months. This may have been due to the “neuropraxia” phenomenon—a temporary deficit of the cavernosal nerves that would abolish any form of erection [
      • Leungwattanakij S.
      • Bivalacqua T.J.
      • Usta M.F.
      • et al.
      Cavernous neurotomy causes hypoxia and fibrosis in rats corpus cavernosum.
      ]. Moreover, low-oxygen tension in cavernosal tissue due to hypoxia following surgery leads to vasoconstriction, corporeal fibrosis, and subsequent ED [

      Saenz de Tejada I, Moreland RB. Physiology of erection, pathophysiology of impotence and implications of PGE1 in the control of collagen synthesis in the corpus cavernosum. In: Goldstein I, Lue TF, editors. The role of alprostadil in the diagnosis and treatment of erectile dysfunction: proceeding of a symposium, August 3–4, 1993, Brook Lodge, Kalamazoo, Michigan. Princeton, NJ: Excerpta Medica, 1993. p. 3–16.

      ].
      Spontaneous EF was absent for most patients in the NS group soon after surgery (only three patients had normal unaided erections postoperatively), but there was a progressive return in a variable proportion of these patients during the follow-up period.
      Penile hemodynamic study on patients after NS radical prostatectomy who had no pharmacological support in the initial year after surgery revealed a progressive incidence of venous leakage varying from 14% at 4 mo to 50% at > 12 mo [
      • Mulhall J.P.
      • Slovick R.
      • Hotaling J.
      • et al.
      Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function.
      ]. Similarly, in the study of Montorsi et al [
      • Montorsi F.
      • Guazzoni G.
      • Strambi L.F.
      • et al.
      Recovery of spontaneous erectile function after nerve-sparing radical reteropubic prostatectomy with and without early intracavernous injections of alprostadil: Results of a prospective randomized trial.
      ], 8 of 15 patients who did not self-inject with alprostadil in the first 4 mo after surgery had a color-PDU diagnosis of venous leakage, compared with only 2 of 12 patients from the treatment group. This can be explained by cavernous tissue fibrosis that occurs secondary to low-oxygen tension on cavernosal tissue due to a decrease of nitric oxide that results in progressive venous incompetence and subsequent ED [
      • Penson D.F.
      • Feng Z.
      • Kuniyuki A.
      • et al.
      General quality of life 2 years following treatment for prostate cancer: what influences outcomes? Results from prostate cancer outcome study.
      ].
      The restoration of EF at 1 yr in this study was observed in17 patients in the NS group (78.8%: 57.8% without erectile aids and 21% with PDE5-I) without compromising the cancer control (within an average of 1 yr of follow-up). No patients in the NNS group showed spontaneous erection, and all of them needed intracavernous self-injection of PGE1.
      Although both groups received erectogenic aids to maintain their erectile and sexual activity, the improvement in EF over time in the NS group was proven by both IIEF and PDU findings, whereas similar improvement was absent in the NNS group. This signifies the crucial role of nerve preservation for the recoverability of EF even if a complete loss of erection occurs during the early postoperative period. On the other hand, the chance of regaining EF even with early erectile rehabilitation is nil when non–nerve sparing techniques are used.
      To emphasize the use of two methods of evaluation used in this study, Table 6 demonstrates that the differences between subjective and objective tools was statistically significant in late months of follow-up (p < 0.05). Moreover, the subjective tools could not reflect the normal objective findings in the PDU study. For example, at month 12, although 13 patients had EDV <5 cm/s, none of them had a normal EF domain. Therefore, use of both techniques for evaluation is mandatory and conclusive.
      Although we aimed from the start to do NS and orthotopic diversions for all patients, who were carefully selected to be comparable even in pathological aspects, the intra-operative surgical findings played an effective role in neurovascular-bundle preservation and in the choice of diversion modality. This may be the reason for our prospective nonrandomized study. To attain conclusive results a randomized clinical trial over a large patient group with a single type of diversion and for long follow-up period should be undertaken.

      5. Conclusion

      The recoverability of erectile function in post–radical cystoprostatectomy patients is mainly related to improvement in veno-occlusive mechanism. The veno-occlusive mechanism was better and progressively returned to normal in the NS group on subjective and objective bases within 1 yr of follow-up. The NS cystectomy technique can ensure good oncologic and sexual outcome (based on the short follow-up period). Therefore, every attempt should be made to preserve the neurovascular bundle during cystoprostatectomy. Use of subjective and objective tools in assessment of the patients is mandatory and conclusive. A randomized clinical study using a single type of diversion over a large group of patients for long-term follow-up should be done to confirm our conclusion.
      Author contributions: Ihab A. Hekal had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
      Study concept and design: El-Bahnasawy.
      Acquisition of data: Hekal.
      Analysis and interpretation of data: Hekal.
      Drafting of the manuscript: Hekal.
      Critical revision of the manuscript for important intellectual content: El-Assmy, Mosbah, Shaaban.
      Statistical analysis: Hekal.
      Obtaining funding: None.
      Administrative, technical, or material support: None.
      Supervision: El-Bahnasawy.
      Other (specify): None.
      Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
      Funding/Support and role of the sponsor: None.

      References

        • Walsh P.C.
        • Donker P.J.
        Impotence following radical prostatectomy: insight into etiology and prevention.
        J Urol. 1982; 128: 492-497
        • Schlegel P.N.
        • Walsh P.C.
        Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.
        J Urol. 1987; 138: 1402-1406
        • Chiang P.H.
        • Wu W.J.
        • Chiang C.P.
        Nerve-sparing radical cystoprostatectomy: 3-year experience.
        Kaohsiung J Med Sci. 1997; 13: 169-174
        • Miyao N.
        • Adachi H.
        • Sato Y.
        • et al.
        Recovery of sexual function after nerve- sparing radical prostatectomy or cystectomy.
        Int J Urol. 2001; 8: 158-164
        • Taniguchi M.
        • Miwa K.
        • Takeuchi T.
        • et al.
        Voiding function and sexual activity in patient following Hautmann neobladder construction.
        Nippon HinyoKika Gakkai Zasshi. 2002; 93: 694-696
        • Martis G.
        • D’Elia G.
        • Diana M.
        • et al.
        Prostatic capsule- and nerve-sparing cystectomy in organ-confined bladder cancer: preliminary results.
        World J Surg. 2005; 29: 1277-1281
        • Zippe C.D.
        • Raina R.
        • Massanyi E.Z.
        • et al.
        Sexual function after male radical cystectomy in a sexually active population.
        Urology. 2004; 64: 682-685
        • Beckendorf V.
        • Hay M.
        • Rozan R.
        • et al.
        Changes in sexual function after radiotherapy treatment of prostate cancer.
        BJU. 1996; 77: 118-123
        • Catalona W.J.
        • Carvalhal G.F.
        • Mager D.E.
        • Smith D.S.
        Potency, continence, and complication rates in 1,870 consecutive radical retropubic prostatectomies.
        J Urol. 1999; 162: 433-438
        • Mulcahy J.J.
        Erectile function after radical prostatectomy.
        Semin Urol Oncol. 2000; 18: 71-75
        • Rosen R.C.
        • Riley A.
        • Wagner G.
        • et al.
        The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
        Urology. 1997; 49: 822-830
        • Zorgniotti A.W.
        • Lefleur R.S.
        Autoinjection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence.
        J Urol. 1985; 133: 139-141
        • Schwartz A.N.
        Radiographic diagnosis and treatment of erectile dysfunction.
        Urology. 1992; 2: 39-50
        • Knispel H.H.
        • Andresen R.
        Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls.
        Eur Urol. 1992; 21: 22-26
        • Pritchett T.R.
        • Schiff W.M.
        • Klatt E.
        • et al.
        The potency-sparing radical cystectomy: does it compromise the completeness of the cancer resection?.
        J Urol. 1988; 140: 1400-1403
        • Brendler C.B.
        • Steinberg G.D.
        • Marshall F.F.
        • et al.
        Local recurrence and survival following nerve-sparing radical cystoprostatectomy.
        J Urol. 1990; 144: 1137-1140
        • Schoenberg M.P.
        • Walsh P.C.
        • Breazeale D.R.
        • et al.
        Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-yr follow-up.
        J Urol. 1996; 155: 490-494
        • Penson D.F.
        • Feng Z.
        • Kuniyuki A.
        • et al.
        General quality of life 2 years following treatment for prostate cancer: what influences outcomes? Results from prostate cancer outcome study.
        J Clin Oncol. 2003; 21: 1147-1154
        • Leungwattanakij S.
        • Bivalacqua T.J.
        • Usta M.F.
        • et al.
        Cavernous neurotomy causes hypoxia and fibrosis in rats corpus cavernosum.
        J Androl. 2003; 24: 239-245
      1. Saenz de Tejada I, Moreland RB. Physiology of erection, pathophysiology of impotence and implications of PGE1 in the control of collagen synthesis in the corpus cavernosum. In: Goldstein I, Lue TF, editors. The role of alprostadil in the diagnosis and treatment of erectile dysfunction: proceeding of a symposium, August 3–4, 1993, Brook Lodge, Kalamazoo, Michigan. Princeton, NJ: Excerpta Medica, 1993. p. 3–16.

        • Mulhall J.P.
        • Slovick R.
        • Hotaling J.
        • et al.
        Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function.
        J Urol. 2002; 167: 1371-1375
        • Montorsi F.
        • Guazzoni G.
        • Strambi L.F.
        • et al.
        Recovery of spontaneous erectile function after nerve-sparing radical reteropubic prostatectomy with and without early intracavernous injections of alprostadil: Results of a prospective randomized trial.
        J Urol. 1997; 158: 1408-1410