Sexual Dysfunction After Radical Prostatectomy

POST–RADICAL PROSTATECTOMY ERECTILE DYSFUNCTION Sexual Dysfunction After Radical Prostatectomy Andrew R. McCullough, MD, FACS Department of Urology, New York University School of Medicine, New York, NY Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may start before the surgery. Men undergoing RRP frequently have some degree of sexual dysfunction. In addition to the psychological stress of the diagnosis, the biopsy may itself have a detrimental effect. After surgery, all men will experience loss of ejaculate, because the organ responsible for ejaculate has been removed. Orgasm quality is adversely affected in many men. Erectile dysfunction is immediate and recovery from it is slow. Initially, phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months for their effect to be maximized. Younger men who have had bilateral nerve-sparing procedures respond the best. Combination treatment with prostaglandin E1 or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5 inhibitor therapy has failed. [Rev Urol. 2005;7(suppl 2):S3-S10] © 2005 MedReviews, LLC Key words: Sexual dysfunction • Radical prostatectomy • Phosphodiesterase-5 inhibitors rostate cancer and its treatment invoke the fear of “castration” and death in many men. Every man is aware of the notoriety of the diagnosis of prostate cancer. Fear of the condition can lead to avoidance of physicians and screening. According to an American Urological Association (AUA) survey of more than 1000 men conducted in 2000 by Roper Starch Worldwide, 74% of men over age 50 felt that the fear of the side effects of treatment caused men to avoid being screened for prostate cancer. Twenty percent of men who were not being screened annually acknowledged that their avoidance was due to fear, both of learning that they had cancer and of the side effects of its treatment. Their wives thought the number was closer to 33%. P VOL. 7 SUPPL. 2 2005 REVIEWS IN UROLOGY S3 Post–Prostatectomy Sexual Dysfunction continued Table 1 Prevalence of Prostate Cancer,* Erectile Dysfunction,† and Hypogonadism‡ by Age 35–44 y 45–54 y 55–64 y 65–74 y 75–84 y 85
y Prostate cancer (%) 7.1 24.6 39.3 23.6 4.9 Erectile dysfunction (%) 4 0.4 26 40 60 60
— Hypogonadism (%) 10 30 45 70 — 2 Data from *Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review, 1975-2000 (available at seer.cancer.gov.csr/1975-2001), †Bacon et al,1 and ‡Morley et al.2 To make matters worse, prostate cancer usually affects men during a period in their lives of waning hormonal, sexual, and erectile function.1,2 More than 50% of men with prostate cancer are at risk for erectile dysfunction (ED), hypogonadism, or both (Table 1). In a study at the Cleveland Clinic, as many as 36% of the men with prostate cancer had ED at the time of diagnosis.3 In a community practice, where the average age at the time of diagnosis is higher, one can anticipate an even higher rate of sexual dysfunction. These fears, as well as the fears of death and incontinence, all surface with the words “Mr. Smith, your PSA level is elevated. I think we need to do a prostate biopsy.” Physical and Psychological Effects of Prostate Biopsy and Cancer Diagnosis The incorporation of prostate-specific antigen (PSA) measurement and the transrectal ultrasound (TRUS) biopsy probe into standard urologic practice had a dramatic impact on the incidence of prostate cancer in the United States and resulted in a trend toward earlier-stage disease at presentation. No longer were men presenting with late-stage disease or undergoing painful perineal biopsies. The biopsy no longer required an S4 VOL. 7 SUPPL. 2 2005 anesthetic or a hospitalization. Within a 7-year period (1986 to 1992), the annual number of cases diagnosed doubled. Most cases are now detected by PSA elevation, rather than by digital rectal examination. Though generally well-tolerated when done under a local anesthetic, cavernous nerves makes them susceptible to injury during extensive transrectal biopsies. The trend toward a greater number of biopsy samples and the increasingly liberal recommendation for prostate biopsy theoretically increase the risk of cavernous nerve injury. Experiencing hematospermia for 6 weeks after the biopsy can increase anxiety about sexual activity. Men who receive news of a positive biopsy result will usually go on to receive treatment that will invariably worsen their function. Men with negative biopsy results are so relieved that they may attribute their decreased function to the stress of the process. More prospective studies should be undertaken to objectively evaluate the risk of ED after prostate biopsy, since it may have some bearing on subsequent post-treatment function. The trend toward a greater number of biopsy samples and the increasingly liberal recommendation for prostate biopsy theoretically increase the risk of cavernous nerve injury. the TRUS biopsy is not without side effects or complications. In a prospective study of 211 men undergoing prostate biopsies, intraoperative pain was considered severe in 20% of the biopsy events. Preoperative anxiety was reported in 64% of biopsy events and was predictive of intraoperative pain. Anxiety continued post-biopsy and peaked before result disclosure. ED attributed to anxiety in anticipation of biopsy was reported in 7% of cases. The ED incidence doubled to 15% at days 7 and 30 after the biopsy, well after the anxiety associated with the biopsy resolved.4 Although it is tempting to attribute the increase in ED to the psychological stress and trauma of the biopsy, it should be remembered that the posterolateral location of the delicate REVIEWS IN UROLOGY Patients receiving the diagnosis of prostate cancer are devastated. The diagnosis is accompanied by a high incidence of anxiety, depression, insult to self-image, sexual dysfunction, and social isolation.5 The patient’s understanding of what is discussed is frequently different from the physician’s perception. Under favorable circumstances, we are lucky if patients remember 50% of what is communicated. In a prospective study of orthopedic patients who were repeatedly educated preoperatively about the risks and benefits of joint replacement until they could answer all questions correctly, postoperatively only 25% remembered the risk of infection, 2% remembered the risk of damage to a nerve or artery, 22% remembered the potential benefits for Post–Prostatectomy Sexual Dysfunction Table 2 Google™ Search Results Search Term Number of Sites Prostate cancer 1,550,000 Prostate cancer surgery 785,000 Prostate cancer radiation 354,000 Prostate cancer alternative approach 260,000 Prostate cancer observation 58,800 Radical prostatectomy 46,400 Prostate cancer cryosurgery 12,200 relief of pain and improved function, and 16% remembered the potential benefit of improved motion.6 Small wonder that a patient and his partner will fail to understand that nerve sparing does not necessarily mean preservation of potency or that, even if there is postoperative potency, it will not be comparable to the preoperative state and may require erectogenic aids. The patient’s concern about cancer cure, survival, and incontinence far outweigh his concern about sorting out details of semantics. After leaving the physician’s office, patients, their partners, or their families will turn to the most readily accessible information source, the Internet. The AUA survey conducted by Roper Starch Worldwide in 2000 found that only 19% of patients sought information on the Internet, but that number has undoubtedly increased. A GoogleTM search in February 2004 revealed more sites than can be investigated in a lifetime (Table 2). Patients are flooded with information and misinformation, and, unfortunately, many sites are purely commercial. There is no peer review or oversight of the Internet. By the time the patient comes to treatment, his understanding of the treatment and its risks and benefits is a combination of the physician’s advice (including possible conflicting second opinions), Internet-based information, and anecdotal information from family and friends. The treatment of prostate cancer invariably results in changes in sexual and erectile function. The degree to which a patient is distressed will depend on his level of pretreatment function and drive, his degree of functional impairment, and his sexual partner. Assuming that the man does not choose observation, his treatment choices are radical surgery, external-beam or interstitial radiation therapy with or without adjuvant hormonal therapy, and cryosurgery. This article focuses on the treatment of sexual dysfunction after radical prostatectomy. during follow-up. The disadvantages are that it is a major operation associated with low but definite mortality ( 0.3%) and significant morbidity: impotence ( 50%), ejaculatory dysfunction (100%), orgasmic dysfunction (50%), incontinence ( 5%-30%), pulmonary embolism ( 1%), rectal injury ( 1%), urethral stricture ( 5%), and transfusion (20%). Sexual dysfunction begins immediately after surgery, with virtually all men experiencing ED. Nocturnal, morning, and psychogenic erections disappear immediately. Although an occasional man will report erections with the indwelling catheter, this occurrence is clearly the exception. The profound loss of nocturnal erections has been reported in both retrospective and prospective series7-9 (Figure 1). The etiology of the immediate loss of nocturnal activity, though debated by experts in the past, is now considered to be the result of intraoperative neurapraxia. There is little evidence of arterial injury on such a large scale after radical prostatectomy.10 Over time, there does appear to be recovery of the nocturnal activity that corresponds with increase in natural erectile function7 (Figure 2). The recovery of erectile function is agonizingly slow, requiring as long as The recovery of erectile function is agonizingly slow, requiring as long as 18 to 24 months, consistent with a slowly resolving neurapraxia. Post-Surgery Erectile Dysfunction The advantages of surgery include definitive staging, possible cure if the tumor is pathologically confined, treatment of concomitant benign prostatic hyperplasia and lower urinary tract symptoms, reliable PSA suppression to unrecordable levels, easy monitoring for recurrent disease, and, arguably, decreased patient anxiety 18 to 24 months, consistent with a slowly resolving neurapraxia.11 As the neurapraxia resolves, the penis becomes increasingly responsive to sildenafil, as one might expect, given that the mechanism of sildenafil and the other phosphodiesterase-5 (PDE-5) inhibitors is dependent on the production of nitric oxide from the nerve endings. Success with sildenafil in the first 6 months can be expected VOL. 7 SUPPL. 2 2005 REVIEWS IN UROLOGY S5 Post–Prostatectomy Sexual Dysfunction continued surgery occurs.13,14 Patients again assume that bilateral nerve sparing is synonymous with preservation of potency, not realizing that few men experience potency that is as good postoperatively as it was preoperatively and that the term “potent” is increasingly defined as erection with the aid of the PDE-5 inhibitors.11 The initial euphoria of having survived the operation is replaced by the reality of incontinence, which resolves for the most part within the first 3 months. Concern over survival and continence is then replaced by concern about potency. Patients do not understand why they have not yet regained erectile function if their nerves were preserved, their PSA level is zero, and their continence is nearly perfect. To make matters worse, many men observe that their penises are shrinking; most of the reduction in penile circumference and length occurs in the first 3 months after surgery.15 These observations are supported with animal models of penile denervation.16,17 Age over 65 years and preoperative sildenafil use predict a poor postoperative recovery of function.18 Many patients and their physicians become discouraged by early unsuccessful attempts with PDE-5 inhibitors, not realizing that a rechallenge at 18 to Pre-op scan 100 0 15 5 Base 100 Rig % 0 Base 15 5 Start Time: 00:00 Cursor Time: 00:00:00 Interval Time: A Post-op scan 1 month 100 0 15 5 Base 100 Rig % 0 Base 15 5 Start Time: 00:00 Cursor Time: 00:00:00 Interval Time: B Figure 1. (A) Preoperative and (B) 1 month postoperative scans showing nocturnal penile tumescence (tum). The profound loss of nocturnal erections after radical prostatectomy is demonstrated. Rig, rigidity. some degree of certainty whether they will have a bilateral, unilateral, or non–nerve-sparing surgery before the 30 EF domain score 120 80 40 re Presurgery baseline S6 VOL. 7 SUPPL. 2 2005 * * * * 10 Postsurgery week 4 REVIEWS IN UROLOGY End of study week 48 48 e W ee k lin e lin se Ba Re A * * 20 0 de r sp N on o de nr Re sp on de r re sp N on o d nRe er sp on de r re sp N on o de nr 0 sp on Figure 2. (A) Nocturnal erection rigidity among study responders and nonresponders and (B) erectile function (EF) domain scores before and after radical prostatectomy. Reprinted with permission from Padma-Nathan et al.7 Duration of rigidity (min) to be very low.12 With increasingly accurate predictors of localized disease, most patients will know with se Tum cm Ba Tip Tum cm 48 % k Tum cm ee Tip Tum cm W % B Sildenafil Placebo Post–Prostatectomy Sexual Dysfunction 24 months postoperatively might result in a successful outcome.12 Experiencing repeated failure, many men lose interest in attempting sexual activity and withdraw from sexual intimacy, despite normal preoperative drive. In a longitudinally followed consecutive cohort of 130 men with intact preoperative erectile function and normal sexual desire at New York University, only 48% and 58% maintained their sexual desire at 3 and 24 months, respectively (data on file). Their partners, not wanting to pressure them or make them feel bad, withdraw sexually as well. The PDE-5 Inhibitors Ultimately, the response to the 3 PDE5 inhibitors seems to be similar, though no direct comparator trials exist for the radical prostatectomy patients. The efficacy of sildenafil was 100 mg. The dropout rate was 27%; 6 of 12 had discontinued because of the return of natural erections, 5 because of a loss of efficacy, and 1 because his spouse had died.20 In a double-blind placebocontrolled study, vardenafil was studied in 440 men after unilateral and bilateral nerve-sparing procedures, starting 6 months after surgery; 70% had severe ED. Among men with bilateral neurovascular bundle sparing, improved erections were reported by 71.1% and 59.7% of patients taking 20 mg and 10 mg of vardenafil, respectively, versus 11.5% of those taking placebo. The average intercourse success rate per patient receiving 20 mg of vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared with 49% and 4% for Many patients and their physicians become discouraged by early unsuccessful attempts with PDE-5 inhibitors, not realizing that a rechallenge at 18 to 24 months postoperatively might result in a successful outcome. first evaluated in the initial pivotal trials when patients who had had prostatectomy were included in the general trials. No stratification was made as to age or nerve-sparing status. An overall response rate of 43% was seen for improvement in erection quality, with a placebo response rate of 14%. In a nonrandomized, nonconsecutive, highly selected population of 91 men taking sildenafil after radical retropubic prostatectomy (RRP), Zippe and associates19 reported a 72% rate of “erections satisfactory for vaginal penetration” in patients who had bilateral nerve sparing versus 50% in men with unilateral nerve sparing. At 3 years, 31 (71%) of the 43 patients who had returned the surveys were still having response to sildenafil. Of these 31 respondents, 10 (31%) had augmented their dose from 50 mg to placebo, respectively. Sildenafil nonresponders were excluded from the studies; more than 50% of men had at least partial response to sildenafil before study entry. The inclusion of such a high proportion of sildenafil responders is reflected in the high response rate in the placebo group of men with mild to moderate ED. The exclusion of sildenafil nonresponders and enrichment with sildenafil responders must be taken into consideration when counseling patients about this medication.21 Tadalafil was studied similarly in a group of 303 men (mean age, 60 years) with preoperative normal erectile function who had undergone a bilateral nerve-sparing RRP 12 to 48 months pre-study, randomized 2:1 to receive tadalafil (n  201) or placebo (n  102).22 The 3 primary endpoints were changes from baseline in the International Index of Erectile Function (IIEF) erectile function domain score and the percentage of positive responses to Sexual Encounter Profile (SEP) questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary endpoints. A priori, a subgroup of patients (n  201) was identified who reported evidence of postoperative tumescence, defined as 50% or more “yes” responses to SEP question 1 (ability to achieve at least some erection) during baseline intercourse attempts, and randomization was stratified based on this criterion. During treatment, for all patients receiving tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence, these values were 69% and 52%, respectively. Sixty-two percent of all patients randomized to tadalafil and 71% of the subgroup patients randomized to tadalafil reported improved erections.22 Eighty percent of the men were previous sildenafil users, although failure to respond to sildenafil was not exclusionary, unlike in the vardenafil study. With overall success rates hovering around 50%, McMahon23 conducted research using high doses of sildenafil in 54 patients with chronic erectile failure. These men had previously failed to respond to a home trial of sildenafil (100 mg) with erections suitable for sexual intercourse. Each man was treated at home with sildenafil at escalating doses of up to 200 mg until either maximal response or intolerable adverse effects occurred. Erectile function was quantified using the erectile function VOL. 7 SUPPL. 2 2005 REVIEWS IN UROLOGY S7 Post–Prostatectomy Sexual Dysfunction continued domain of the IIEF before treatment with sildenafil 100 mg and with maximal dose of sildenafil, and using a global efficacy question after 4 weeks of treatment. The mean age of the study group was 59.6 years, with 11 (20%) of 54 having post-RRP ED. Thirteen (24.1%) of 54 responded to sildenafil at a median maximal dose of 200 mg; 4 required 150 mg, and 9 required 200 mg. Forty-one (76%) of 54 had no response to sildenafil. Mean scores for IIEF questions 3 and 4 were 1.5 and 1.4 at baseline, 2.2 and 1.9 with sildenafil 100 mg, 2.8 and 2.5 with sildenafil 150 mg, and 3.0 and 2.9 with sildenafil 200 mg, respectively. After 4 weeks, treatment was regarded as having improved Options After Initial PDE-5 Inhibitor Failure The options for nonresponders to PDE-5 inhibitors include injection therapy, intraurethral prostaglandin, vacuum erection devices, and penile implants. The concomitant use of the PDE-5 inhibitors is discouraged in the regulatory documents for all 3 PDE-5 inhibitors. Nonetheless, there is a rationale for combination therapy. Corpus cavernosum smooth muscle relaxation, and hence penile erection, is regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Intraurethral or intracorporeal prostaglandin E1 increases both second messengers. In men with failure of PDE-5 inhibition or prostaglandin therapy, a synergistic effect might occur with combination therapy. erections in 37%, 46.3%, and 68% of patients taking sildenafil 100 mg, 150 mg, and 200 mg, respectively. Thirty-four (63%) of 54 patients reported adverse effects with maximaldose sildenafil, including headache (19), facial flushing (32), dyspepsia (14), nasal congestion (11), dizziness (5), and visual disturbances (5). Four (31%) of 13 responders refused to continue treatment because of adverse effects. It was concluded that sildenafil at doses of up to 200 mg was an effective salvage therapy for 24.1% of previous sildenafil nonresponders but was limited by a significantly higher incidence of adverse effects and a 31% treatment discontinuation rate. Highdose studies have not been carried out for vardenafil or tadalafil. Currently the maximum doses approved by the U.S. Food and Drug Administration are 100 mg, 20 mg, and 20 mg for sildenafil, vardenafil, and tadalafil, respectively.23 S8 VOL. 7 SUPPL. 2 2005 Therefore, in men with failure of PDE-5 inhibition or prostaglandin therapy, a synergistic effect might occur with combination therapy. Nehra and coworkers24 studied 28 patients using sildenafil and the Medicated Urethral System for Erection (MUSE) (mean age, 59 years)—17 of whom had undergone radical prostatectomy and 11 of whom had a diagnosis of organic ED—for 30 months. Treatment with either 100 mg of sildenafil citrate and/or 1000 g of MUSE had failed in these patients. Combination therapy was initiated using 100 mg of sildenafil citrate orally 60 minutes before intercourse and 500 g of MUSE intraurethrally immediately before intercourse. At 30 months, all 28 patients reported erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. It was concluded that combination REVIEWS IN UROLOGY therapy, incorporating both pathways, cAMP and cGMP, might succeed when single therapies fail.24 Along those lines, in my practice, I also combine sildenafil with intracorporeal injections in men after radical prostatectomy who are experiencing failure of intracorporeal injection therapy. The combined use of sildenafil with injection or MUSE therapy, though logistically cumbersome, has allowed some patients to avoid implant therapy.25 At the AUA in 2003, we reported erectogenic aid usage longitudinally in 200 men with preoperative normal sexual function who had had bilateral nerve-sparing surgery.26 At 3 months, 52% were using sildenafil, although less than 10% were able to achieve and maintain erections satisfactory for intercourse, versus 35% in subsequent follow-up at 24 months. At 24 months, 50% of the men were still using sildenafil, 27% were using injection therapy, and 22% were using nothing. Thus, erectile function after surgery can still be improved. Post-Surgery Orgasmic Function Orgasmic function after radical prostatectomy is infrequently discussed or reported. In another prospective longitudinal study on quality of life after RRP at New York University, 230 consecutive patients completed questionnaires presurgery and at 3, 6, 12, and 24 months after surgery and were asked to rate their ability to achieve orgasms as very good, good, fair, poor, or very poor.27 The average age was 59 years; 31% were younger than 55 years, 45% were between 55 and 65 years, and 23% were older than 65 years. Seventy-six percent of men described good preoperative orgasmic function (n  173). Men with good or very good preoperative orgasmic quality suffered a loss in orgasmic quality that improved slightly at each time interval (34% Post–Prostatectomy Sexual Dysfunction had improved at 3 months, 40% at 6 months, 48% at 12 months, and 47% at 24 months). Approximately 15% of men with fair or poor preoperative orgasms had improved orgasmic quality at 24 months. Longitudinal orgasmic quality improvement correlated strongly with age, erectile function, sexual desire, and successful vaginal sex at virtually all time points (P  .05). Urinary control did not strongly affect orgasmic quality. Treatment with erectogenic aids (sildenafil or Trimix) was associated with improved orgasmic function during the first year, after which it had no impact. The cause of the decreased orgasmic function is undoubtedly multifactorial, since the man has to deal with the psychological stress of the diagnosis and the surgery as well his diminished sexual function. Summary Sexual function is unquestionably compromised after radical prostatectomy. Preoperative apprehension, misinformation, and misinterpretation lead to unrealistic expectations on the part of patients and their partners. Some patients misinterpret the loss of ejaculate as the inability to have an orgasm and do not even attempt sexual activity. The immediate loss of erectile function leads to sexual with- drawal and a decrease in libido. The lack of effectiveness of the PDE-5 inhibitors in the first 6 months postoperatively only exacerbates the problem. As nerve function recovers, patients increasingly respond to the PDE-5 inhibitors. Younger age, bilateral nerve sparing, and better preoperative function will result in better postoperative response to oral therapy. Combination treatment has a limited role. Early sexual rehabilitation may have a therapeutic role as well as a role in maintaining sexual intimacy during the postoperative period. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003;139:161-168. Morley JE, Kaiser FE, Perry HM 3rd, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997;46:410-413. Schover LR, Fouladi RT, Warneke CL, et al. Defining sexual outcomes after treatment for localized prostate carcinoma. Cancer. 2002;95: 1773-1785. Zisman A, Leibovici D, Kleinmann J, et al. The impact of prostate biopsy on patient well-being: a prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001;165:445-454. Turns D. Psychosocial issues: pelvic exenterative surgery. J Surg Oncol. 2001;76:224-236. Hutson MM, Blaha JD. Patients’ recall of preoperative instruction for informed consent for an operation. J Bone Joint Surg Am. 1991;73:160-162. Padma-Nathan H, McCullough A, Guiliano F, et al. Postoperative nightly administration of sildenafil citrate significantly improves the 13. 14. 15. 16. 17. return of normal spontaneous erectile function after bilateral nerve-sparing radical prostatectomy. J Urol. 2003;169:375. Fraiman M, Lepor H, McCullough A. Nocturnal penile tumescence activity in 81 patients presenting with erectile dysfunction after nerve sparing radical prostatectomy. J Urol. 1991; 161:179. McCullough A, Levine L, Padma-Nathan H. A prospective study of preoperative and postoperative nocturnal penile tumescence (npt) in men undergoing bilateral nerve sparing radical prostatectomy (BNSRRP). J Androl. 2002; 23:59. McCullough A, Woo K, Telegrafi S, Lepor H. Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP. Int J Impot Res. 2002;14:462-465. Walsh PC. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. J Urol. 2000;164:242. Hong EK, Lepor H, McCullough AR. Time dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP). Int J Impot Res. 1999;11(suppl 1):S15-S22. Partin AW, Kattan MW, Subong EN, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA. 1997;277:1445-1451. Blute ML, Bergstralh EJ, Partin AW, et al. Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer. J Urol. 2000;164:1591-1595. Fraiman MC, Lepor H, McCullough AR. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol. 1999;3:109-115. Klein LT, Miller MI, Buttyan R, et al. Apoptosis in the rat penis after penile denervation. J Urol. 1997;158:626-630. User HM, Hairston JH, Zelner DJ, et al. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol. 2003;169:1175-1179. Main Points • Although as many as 36% of men with prostate cancer have been shown to have erectile dysfunction (ED) at the time of diagnosis, prostate biopsy itself can worsen sexual function through its accompanying anxiety and by possible injury to the cavernous nerves. Both nerve-sparing and non–nerve-sparing procedures are associated with significant ED post-prostatectomy. • As post-surgery neurapraxia slowly resolves, patients’ response to phosphodiesterase-5 inhibitors increases. Initial failures of therapy might be followed by successful rechallenge at 18 to 24 months postoperatively. • Sildenafil, vardenafil, and tadalafil have similar efficacy in patients with ED, although no direct comparator trials exist for radical prostatectomy patients. • One study showed that maximizing the dose of sildenafil was effective in 24.1% of initial nonresponders to sildenafil treatment but was limited by a significantly higher incidence of adverse effects; other options for nonresponders include injection therapy, intraurethral prostaglandin E1, vacuum erection devices, and penile implants. Combination therapy has a limited role, but sildenafil used with prostaglandin E1 may have a beneficial synergistic effect in some patients with previous nonresponse. VOL. 7 SUPPL. 2 2005 REVIEWS IN UROLOGY S9 Post–Prostatectomy Sexual Dysfunction continued 18. 19. 20. 21. S10 McCullough A, Ip C, Lepor H. The effect of age at the time of surgery on potency after nerve sparing radical prostatectomy. Int J Impot Res. 2001;13:S68. Zippe CD, Jhaveri FM, Klein EA, et al. Role of Viagra after radical prostatectomy. Urology. 2000;55:241-245. Raina R, Lakin MM, Agarwal A, et al. Long-term effect of sildenafil citrate on erectile dysfunction after radical prostatectomy: 3-year follow-up. Urology. 2003;62:110-115. Brock G, Nehra A, Lipshultz LI, et al. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic VOL. 7 SUPPL. 2 2005 22. 23. 24. prostatectomy. J Urol. 2003;170:1278-1283. Montorsi F, Nathan HP, McCullough A, et al. Tadalafil in the treatment of erectile dysfunction following bilateral nerve-sparing radical retropubic prostatectomy: a randomized, double-blind, placebo-controlled trial. J Urol. 2003;172: 1036-1041. McMahon CG. High dose sildenafil citrate as a salvage therapy for severe erectile dysfunction. Int J Impot Res. 2002;14:533-538. Nehra A, Blute ML, Barrett DM, et al. Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring REVIEWS IN UROLOGY 25. 26. 27. noninvasive therapy. Int J Impot Res. 2002;14 (suppl 1):S38-S42. Mydlo JH, Volpe MA, Macchia RJ. Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil monotherapy. Eur Urol. 2000;38:30-34. McCullough A, Kau E, Kaci L, Lepor H. A 12 month longitudinal study of treatment seeking behavior in 200 men after radical retropubic prostatectomy. J Urol. 2000;169:379. McCullough AR, Kau E, Lepor H. A 24 month longitudinal study of orgasmic quality in 228 men after radical retropubic prostatectomy. J Urol. 2004;171:4, 39.