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Doi:10.1016/j.urology.2004.05.056

ADULT UROLOGY
SEXUAL FUNCTION AFTER MALE RADICAL CYSTECTOMY IN CRAIG D. ZIPPE, RUPESH RAINA, ERIC Z. MASSANYI, ASHOK AGARWAL, J. STEPHEN JONES, ABSTRACT
Objectives. To assess sexual dysfunction in sexually active men after radical cystectomy (RC) and to
determine whether sildenafil citrate can improve erectile dysfunction after surgery.
Methods. The baseline and follow-up data from 49 sexually active male patients (mean age 57.8 Ϯ 9.1
years) undergoing RC (1995 to 2002) were obtained. Of the 49 patients, 16 (33%) had undergone
nerve-sparing RC; 38 (78%) had undergone orthotopic diversion; 8 (16%) had undergone ileal conduit
diversion; and 3 (6%) had undergone cutaneous continent diversion. The data were assessed using the
abridged 5-item International Index of Erectile Function questionnaire, referred to as the Sexual Health
Inventory for Men (SHIM).
Results. At a mean follow-up of 47.6 Ϯ 22.7 months, the total mean SHIM score decreased from 22.08 Ϯ
3.96 to 4.33 Ϯ 5.72 after RC (P Ͻ0.05). Of the 49 patients, 42 (86%) did not have erections sufficient for
vaginal penetration. Of these 42 patients, 22 (52%) tried sildenafil citrate. Of these 22 patients, only 2 (9%)
responded positively, with a total mean SHIM score of 23.50 Ϯ 2.12. Although the mean SHIM score after
orthotopic substitution (5.24 Ϯ 6.21) was statistically significant compared with that after ileal conduit (1.13
Ϯ 0.33) and cutaneous continent (1.33 Ϯ 0.58) diversions, this was not clinically significant.
Conclusions. Male erectile dysfunction after RC is a prevalent problem. In our series, only 9 (14%) of 49 sexually
active men were potent after surgery. Of these 9 potent patients, 8 (89%) had undergone nerve-sparing RC. Of
concern, only 52% of the patients with erectile dysfunction sought treatment after RC.
UROLOGY 64: 682–686,
Radicalcystectomy(RC)hasbeenthestandardfor otherquality-of-lifeissueafterRC.Wechoseasex-
treatment of aggressive superficial bladder can- ually active population in whom erectile function cer and invasive The endpoints after this was an important quality-of-life issue before sur- operation have focused on cure, urethral recurrence, gery. We validated our responses in this subset, using the abridged 5-item version of the Interna- bundles are usually removed or damaged with re- tional Index of Erectile Function (IIEF-5) ques- moval of the Recent interest in quality-of- tionnaire, referred to as the Sexual Health Inven- life issues has stimulated the evolution of orthotopic treatments they had sought and assessed their re- has provided the momentum for assessing other In this study, we addressed sexual function, an- MATERIAL AND METHODS
STUDY SUBJECTS AND DESIGN
R. Raina and C. D. Zippe are members of the speakers bureau for The Cleveland Clinic Institutional Review Board approved this study, and all patients granted informed consent. Study From the Center for Advanced Research in Human Reproduc- participants were a self-selected, nonrandomized group who tion, Infertility and Sexual Function and the Glickman Urological had undergone RC, were alive in 2003, and had completed the Institute, Cleveland Clinic Foundation, Cleveland, Ohio necessary questionnaires. We obtained data on 49 male pa- Reprint requests: Craig D. Zippe, M.D., Glickman Urological tients (mean age 57.8 Ϯ 9.1 years) who were sexually active Institute, Marymount, Cleveland Clinic Foundation, 1200 before surgery and had undergone RC at the Glickman Uro- McCrackin Road, Suite 451, Garfield Heights, OH 44125 logical Institute from May 1995 to March 2002. These patients Submitted: August 11, 2003, accepted (with revisions): May completed the SHIM (IIEF-5) questionnaire or the IIEF-15 (before 1999) before surgery (4 months or less), after RC (1 SHIM (IIEF-5) analysis: baseline and after
radical cystectomy
Baseline Before RC
SHIM (IIEF-5) Domains
KEY: SHIM ϭ Sexual Health Inventory for Men; IIEF-5 ϭ 5-item (short form) International Index of Erectile Function; RC ϭ radical cystectomy; Q ϭ question.
Data presented as mean
Ϯ SD.
Wilcoxon rank-sum test used to compare preoperative and postoperative changes across study groups.
Each IIEF-5 domain scored from 0 to 5; 0
ϭ did not attempt intercourse; 1 ϭ never/occasionally; 2 ϭ less than half the time;3 ϭ sometimes/half the time; 4 ϭ more than half the time; 5 ϭ almost always; total IIEF-5 score calculated by totaling andtaking the mean of the responses to all 5 domains of IIEF-5.
* P Ͻ0.05 after RC vs. baseline. year or longer), and after the use of sildenafil citrate or any used to assess changes from baseline. Wilcoxon rank sum erectile aid for erectile dysfunction (ED). Medical records tests were used to compare the preoperative and postoper- were obtained and reviewed to assess the baseline medical data ative changes across study groups. Statistical significance and social history, as well as the type of urinary diversion and was assessed with a two-tailed test at P Ͻ0.05. Computa- nerve-sparing surgery. When the operative report did not tions used Statistical Analysis Systems, version 8.1, soft- specify any consideration or protection of the neurovascular bundles, the procedure was deemed a non-nerve-sparing pro-cedure.
The mean level of preoperative sexual activity before surgery was 2.0 Ϯ 1.2 per week. Of these 49 patients, 38 (78%) had At a mean follow-up of 47.6 Ϯ 22.7 months, 42 undergone orthotopic urinary diversion (Studer pouch), 8 (16%)had undergone ileal conduit diversion, and 3 (6%) had under- (86%) of the 49 patients were unable to achieve gone cutaneous continent diversion (Indiana). Only 16 (33%) of vaginal penetration after surgery. The mean total the 49 patients had undergone nerve-sparing procedures. Of the SHIM (IIEF-5) score of the 49 patients at baseline 16 patients who had undergone nerve-sparing RC, 6 had patho- was 22.1 Ϯ 4.0. After surgery, the mean total SHIM logic Stage T1, 2 had Stage T2a, and 8 had Stage T2b, and all had score for the entire group was 4.33 Ϯ 5.72 negative surgical margins. The mean follow-up interval was 47.6 Ϯ 22.7 months after surgery. Of these 49 patients, 2 developed Of these 49 patients, 7 had erections sufficient recurrent cancer. When comorbidities were assessed in the 49 for vaginal penetration at a mean of 17.1 Ϯ 4.1 patients, hypertension was found in 35%, diabetes in 6%, and months after surgery. Those 7 patients had a mean total baseline SHIM score of 21.1 Ϯ 4.1 and a meantotal postoperative score of 16.6 Ϯ 4.9 at a mean SURVEYS AND DATA ASSESSMENT
follow-up of 44.4 Ϯ 25.1 months. When analyzing Sexual function was assessed at baseline (preoperative), af- these 7 patients for common denominators to ex- ter RC, and after treatment using the abridged 5-item IIEF-5questionnaire, referred to as the This questionnaire plain their potency, 6 (86%) of the patients had was used to define and validate the degree of sexual dysfunc- undergone a nerve-sparing procedure. Although tion in our surgical population. Specific domains analyzed in this subgroup’s mean age of 51.0 Ϯ 10.9 years was the SHIM questionnaire include erection confidence, erection lower than the remaining 42 patients’ mean age firmness, ability to maintain an erection, maintenance fre- (58.9 Ϯ 8.4 years), the difference was not statisti- quency, and intercourse satisfaction. This questionnaire pro-vided us with a comprehensive assessment of baseline, post- cally significant (P ϭ 0.055). Additionally, the in- operative, and post-treatment sexual function in this pop- cidence of comorbid disorders (hypertension, dia- ulation of patients. Responses were scored from 0 to 5. The betes, coronary artery disease) was similar in both total SHIM score was calculated by adding responses from all the sexually active and impotent subgroups, with a five domains. The mean baseline scores to the questions were rate of 43% (3 of 7) and 48% (20 of 42), respec- calculated and compared with the postoperative scores to as-sess the change in response.
In addition to the SHIM questionnaire, we asked patients to In the other 42 patients who had no potency estimate their approximate frequency of sexual intercourse at sufficient for vaginal penetration, 4 were able to baseline, after surgery, and after treatment. Patients’ spouses achieve erections with an erectile aid or medical or partners were also asked to rate their level of satisfaction, therapy (sildenafil citrate). Two patients re- sponded successfully to sildenafil citrate. Two S
other patients were using erectile aids to achieve TATISTICAL ANALYSIS
The mean and standard deviation were calculated for all erections, one with a vacuum constriction device the domains of the SHIM questionnaire. Paired t tests were and one using intracavernosal injection therapy. In UROLOGY 64 (4), 2004
TABLE II.
SHIM (IIEF-5) analysis: treatment with sildenafil citrate and erectile aids
Baseline Before
Treatment Response and Type
After Treatment
Negative response to sildenafil (n ϭ 20) Positive response to erectile aids (n ϭ 2) Abbreviations as in Data presented as mean Ϯ SD.
Wilcoxon rank sum test used to compare preoperative and postoperative changes across study groups.
Each IIEF-5 domain scored from 0 to 5; 0
ϭ did not attempt intercourse; 1 ϭ never/occasionally; 2 ϭ less than half the time; 3 ϭ sometimes/half the time; 4 ϭ more than halfthe time; 5 ϭ almost always; total IIEF-5 score calculated by totaling and taking the mean of the responses to all 5 domains of IIEF-5.
* P Ͻ0.05 after RC vs. baseline. † P Ͻ0.05 after RC vs. after treatment. TABLE III.
SHIM (IIEF-5) analysis: stratified by type of
urinary diversion
Baseline Before
Urinary Diversion
Abbreviations as in Data presented as mean Ϯ SD.
Wilcoxon rank sum test used to compare preoperative and postoperative changes across study groups.
Each IIEF-5 domain scored from 0 to 5; 0
ϭ did not attempt intercourse; 1 ϭ never/occasionally; 2 ϭ less than half the time;3 ϭ sometimes/half the time; 4 ϭ more than half the time; 5 ϭ almost always; total IIEF-5 score calculated by totaling andtaking the mean of the responses to all 5 domains of IIEF-5.
* P Ͻ0.05, after RC vs. baseline. † P Ͻ0.05, orthotopic substitution vs. ileal conduit/continent cutaneous. the 42 patients who were impotent, our data indi- age of 58.9 Ϯ 8.4 years. Seven (14%) of the 49 cated that 22 (52%) attempted sildenafil citrate, patients were naturally potent after surgery, and with only 2 (9%) having responses sufficient for 6 of those 7 (86%) had undergone a nerve-spar- ing procedure. Of concern, only 52% of this sex- We stratified the degree of ED (using SHIM ually active series sought treatment for their ED.
scores) by the type of urinary diversion. The differ- This study also points out the important impact ence in the mean total SHIM score of 5.24 Ϯ 6.21 of the postoperative treatment of patients with ED.
after orthotopic substitution was statistically sig- Of the 42 patients with ED after RC, 20 (47%) did nificant (P Ͻ0.05) compared with that after ileal not seek treatment. This fact emphasizes the im- conduit (mean total SHIM score 1.13 Ϯ 0.33) and portance of preoperative counseling and earlier ag- cutaneous continent (mean total SHIM score 1.33 gressive treatment and consultation after surgery.
Currently, these patients often have a discussion ference was not as clinically significant, because regarding their ED 12 to 18 months after surgery.
the difference between “almost never or never” This delay in addressing this issue after RC may does not differ in the SHIM questionnaire from discourage patients and may explain why many sexually active patients in our study did not seektreatment after RC.
In our series, only 2 (9%) of 22 patients re- The results of this study have important signif- sponded to sildenafil citrate as defined by success- icance in the treatment of bladder cancer. Al- ful vaginal penetration. It is well known that pres- though RC has focused primarily on cure, recur- ervation of the neurovascular bundles is vital for the success of sildenafil Sildenafil citrate our results suggest that ED is an important com- does not work as a phosphodiesterase type 5 inhib- plication after this procedure that has not been itor when nitric oxide is not released from the neu- well recognized. ED was a prevalent problem in rovascular bundle. The 2 patients who responded our study, occurring in 42 (86%) of 49 sexually to sildenafil citrate had preservation of neurovas- active men after RC. These 42 patients were sex- cular bundles. It is unclear from the operative re- ually active before surgery, with a mean fre- ports how many of the other 20 patients had un- quency of 2.0 Ϯ 1.3 times per week and a mean dergone nerve-sparing RC. It appears that most UROLOGY 64 (4), 2004
were non-nerve-sparing procedures, explaining 4. Stein JP: Indications for early cystectomy. Semin Urol our low response rate to sildenafil citrate.
Oncol 18: 289 –295, 2000.
5. Herr HW: Extent of surgery and pathology evaluation has an impact on bladder cancer outcomes after radical cys- modified surgical technique (nerve sparing) re- tectomy. Urology 61: 105–108, 2003.
sulted in the increased postoperative potency of 6. Schlegel PN, and Walsh PC: Neuroanatomical ap- individuals who had undergone radical cys- proach to radical cystoprostatectomy with preservation of sex- toprostatectomy. Of the 11 patients who had un- ual function. J Urol 138: 1402–1406, 1987.
dergone nerve-sparing procedures in this study, 7. Hart S, Skinner EC, Meyerowitz BE, et al: Quality of life after radical cystectomy for bladder cancer in patients with an 9 (82%) had regained sexual potency after 1 ileal conduit, or cutaneous, or urethral Kock pouch. J Urol In 1990, using a larger sample size, Bren- 162: 77– 81, 1999.
dler et reported that 27 (52%) of 52 patients 8. Matsuda T, Aptel I, Exbrayat C, et al: Determinants of who had undergone nerve-sparing cystopros- quality of life of bladder cancer survivors five years after treat- tatectomy regained potency after 1 year. Since ment in France. Int J Urol 10: 423– 429, 2003.
9. Rosen RC, Cappelleri JC, Smith MD, et al: Development that landmark study, others have reported simi- and evaluation of an abridged, 5-item version of the Interna- lar rates of potency after nerve-sparing RC, rang- tional Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impotence Res 11: 319 –326,
neurovascular bundles appears to be essential for the return of sexual potency after RC.
10. Walsh PC: Radical retropubic prostatectomy, in Walsh PC, Gittes RF, Pelmutter AD, et al (Eds): Campbell’s Urology, The 9 patients in our study who were sexually 5th ed. Philadelphia, WB Saunders, 1986, pp 2754 –2775.
active after RC (defined by vaginal penetration) 11. Walsh PC, and Mostwin JL: Radical prostatectomy and had only one common denominator. Eight (89%) cystoprostatectomy with preservation of potency: results us- of these 9 patients had undergone nerve-preserv- ing a new nerve-sparing technique. Br J Urol 56: 694 – 697,
ing RC. Although these 9 patients had a mean age 12. Brendler CB, Steinberg GD, Marshall FF, et al: Local of 51.0 Ϯ 10.9 years, the difference from the re- recurrence and survival following nerve-sparing radical cys- maining 42 patients’ mean age (58.9 Ϯ 8.4 years) toprostatectomy. J Urol 144: 1137–1140, 1990.
was not statistically significant. We also found that 13. Koraitim M, and Khalil R: Preservation of urosexual the incidence of comorbidity (43%) in these 9 pa- functions after radical cystectomy. Urology 39: 117–121,
tients was similar to that of the impotent subgroup 14. Marshall FF, Mostwin JL, Radebaugh LC, et al: Ileocolic neobladder post-cystectomy: continence and potency. J Urol
145: 502–504, 1991.
15. Schoenberg MP, Walsh PC, Breazeale DR, et al: Local CONCLUSIONS
recurrence and survival following nerve-sparing radical cys-toprostatectomy for bladder cancer: 10-year followup. J Urol Although surgical cure is always the priority, ED 155: 490 – 494, 1996.
will become a more accountable endpoint in the 16. Venn SN, Popert RM, and Mundy AR: “Nerve-sparing” future. Similar to what occurred in surgical pros- cystectomy and substitution cystoplasty in patients of either sex: limitations and techniques. Br J Urol 82: 361–365, 1998.
protocols for bladder cancer will cause stage migra- 17. Spitz A, Stein JP, Lieskovsky G, et al: Orthotopic uri- nary diversion with preservation of erectile and ejaculatory tion and provide earlier indications for RC. Remov- function in men requiring radical cystectomy for nonurothe- ing earlier staged disease will make more patients lial malignancy: a new technique. J Urol 161: 1761–1764,
eligible for nerve-sparing procedures. Addition- ally, as younger patients are diagnosed, the mo- 18. Zagaja GP, Mhoon DA, Aikens JE, et al: Sildenafil in the mentum for a “quality-of-life cystectomy” will con- treatment of erectile dysfunction after prostatectomy. Urology
56: 631– 634, 2000.
tinue to increase as patients’ expectations change.
19. Zippe CD, Jhaveri FM, Klein EA, et al: Role of Viagra Redefining the future “quality-of-life cystectomy” after radical prostatectomy. Urology 55: 241–245, 2000.
is in evolution as we continue to perform more 20. Zippe CD, Kedia AW, Kedia K, et al: Treatment of erec- orthotopic urinary diversions and consider more tile dysfunction after radical prostatectomy with sildenafil ci- patients eligible for neurovascular preservation.
trate (Viagra). Urology 52: 963–966, 1998.
1. Stein JP, and Skinner DG: Results with radical cystec- This is a nonrandomized, self-selected group of 49 men tomy for treating bladder cancer: a ‘reference standard’ for (mean age 58 Ϯ 9 years) who underwent RC during a 7-year high-grade, invasive bladder cancer. BJU Int 92: 12–17, 2003.
period at one institution. All men were sexually active before 2. Santucci RA, Park CH, Mayo ME, et al: Continence and surgery. Only 16 of 49 patients underwent a “nerve-sparing” urodynamic parameters of continent urinary reservoirs: com- procedure, and 84% received a continent urinary diversion.
parison of gastric, ileal, ileocolic, right colon and sigmoid seg- The patients were evaluated for sexual function by the SHIM ments. Urology 54: 252–257, 1999.
questionnaire preoperatively, 1 year or more after surgery, and 3. Wei JT, Dunn RL, Marcovich R, et al: Prospective as- after using sildenafil citrate. The mean follow-up was 48 Ϯ 23 sessment of patient reported urinary continence after radical prostatectomy. J Urol 164: 744 –748, 2000.
Only 9 (18%) of these 49 men were able to achieve erections UROLOGY 64 (4), 2004

Source: http://www.clevelandclinic.org/reproductiveresearchcenter/docs/agradoc155.pdf

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