Currently, there are many well-established therapeutic options for early prostate cancer, and therefore, it is difficult for both urologists and patients to choose the optimal treatment. It is essential for urologists to counsel their patients according to reliable information about the advantages and disadvantages of each therapeutic option. We picked the topic for this issue, “Characteristics and management of erectile dysfunction after various treatments for prostate cancer,” because erectile dysfunction (ED) is one of the most frequent adverse events encountered in the management of prostate cancer. We invited six specialists to review each therapeutic option: radical prostatectomy, laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, external beam radiotherapy, brachytherapy, and androgen deprivation therapy (ADT). Among these modalities, surgical interventions tend to induce a quick drop in erectile function with slow postoperative recovery. Early postoperative rehabilitation has been introduced, aiming at the early recovery of ED. On the contrary, radiation therapy tends to maintain the patient's erectile function for a while after treatment but it gradually decreases. ADT may compromise not only the erectile function but also the libido level, and may result in significant deterioration of the patient's quality of life. We hope these reviews will help urologists to counsel their patients with regards to decision-making in the management of early prostate cancer. Jintetsu Soh md phd Deputy Editor Erectile dysfunction and urinary incontinence are major complications after radical prostatectomy (RP). While general health-related quality of life (QOL) usually recovers within about 6 months, sexual dysfunction remains and deteriorates patient QOL.1 To preserve sexual functions, a nerve-sparing procedure during RP, as initially described by Walsh et al.2 has become widely accepted and performed. In a 5-year follow-up study assessing the impact of nerve sparing on recovery of sexual function conducted in our institution, bilateral nerve-sparing RP is identified as showing better recovery and preservation in postoperative sexual functions than unilateral and non-nerve-sparing RP.1 The first thing we should do to preserve sexual function is thus try to perform nerve-sparing surgery, unless this interferes with oncological outcomes. Unfortunately, however, even when we have successfully performed bilateral nerve-sparing RP, only about 55% of subjects showed full return to baseline sexual function.1 At present, we would have to say that traditional nerve-sparing procedures have certain limits. We have recently reported that nerve fibers distributed on the prostate capsule, particularly those outside the neurovascular bundle, contribute to erection.3 Recent advances in surgical techniques for RP that pay increasing attention to preserving as many nerve fibers responsible for erectile function as possible may change the results of nerve-sparing RP. Penile rehabilitations for erectile dysfunction, such as oral phosphodiesterase type 5 inhibitors (PDE5i), intracavernous vasoactive injections, intra-urethral application of prostaglandin E1 (PGE-1) and vacuum constriction devices, have attracted attention. The purpose of penile rehabilitation is to preserve cavernosal tissue property, and thereby promote the chances of recovery of postoperative erectile ability. In these methods, we have used oral PDE5i as a first-line treatment for patients complaining of erectile dysfunction after RP, although the efficacy of PDE5i in penile rehabilitation programs has not yet been supported by definitive evidence in humans. Between June 2003 and July 2008, a total of 269 patients with newly diagnosed localized prostate cancer (T1–3N0M0) were treated with RP in our institution. Among these, 103 patients who underwent bilateral nerve-sparing RP confirmed by intraoperative electrophysiological testing were recruited (average age at the time of surgery was 63.2 years [47–76 years]). A PDE5i (sildenafil, vardenafil or tadalafil) was prescribed when patients complained of erectile dysfunction and demanded pharmacotherapy, and patients were instructed to take the medicine once a week. The 103 patients were then classified into two groups: a PDE5i group and a non-PDE5i group. Recovery of sexual function was assessed and compared between the groups. Sexual function was estimated using the sexual function domain of the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) until March 2006 and subsequently using the Extended Prostate Cancer Index Composite (EPIC) questionnaire preoperatively and at 1, 3, 6, 12, 18, 24 and 36 months after RP. Scores for the sexual function domain of the UCLA-PCI were translated into scores for the sexual function domain of the EPIC according to a previous article.4 Of the 103 patients, 100 (97.1%) returned the questionnaire and the collection rate was 91.5%. Mean follow-up period was 39.4 months. Among these, 58 patients took postoperative PDE5i (PDE5i group) and 45 did not (non-PDE5i group). In the PDE5i group, median interval until start of PDE5i after RP was 91 days (range: 1–1063 days). Figure 1 shows the longitudinal changes in sexual function score of the PDE5i and non-PDE5i groups, respectively. Scores for sexual functions that initially declined to the nadir by around 1 month after RP, gradually improved in both the PDE5i and the non-PDE5i groups. However, improvement of sexual function was significantly earlier and greater in the PDE5i group compared with the non-PDE5i group. Our data shows better recovery of sexual function after RP in the PDE5i group. PDE5i group showed better recovery of postoperative sexual function compared with non-PDE5i group. EPIC, Extended Prostate Cancer Index Composite. , phosphodiesterase type 5 inhibitors (PDE5i); , Non-PDE5i. The efficacy of PDE5i on recovery for erectile dysfunction after RP in humans remains controversial.5 Although further research is required to clarify this issue, our data suggest that PDE5i can promote recovery of sexual function after RP. Yasuhiro Kaiho md phd Department of Urology, Tohoku University School of Medicine,Sendai, Japan [email protected] Laparoscopic radical prostatectomy (LRP) is a widely used minimally-invasive surgical technique for localized prostate cancer. The use of this procedure continues to increase in many countries worldwide. In a nation-wide survey performed by the Japanese Association for Minimum-Incision Endoscopic Surgery with the support of the Japanese Urological Association, 13% of the institutions that responded to the survey were performing minimally invasive surgery, and more than half of them were aiming at introduction of the surgery in the near future.6 The goal of minimally invasive surgery such as LRP is to achieve a lower perioperative complication rate, earlier postoperative recovery, good oncological results, and better functional outcome including preservation of potency and earlier recovery of urinary continence. Previous reports have demonstrated that the 12-month potency rate after LRP ranges from 40% to 75%.7 The broad range in outcomes for erectile function (EF) rate after LRP is due to several study design factors, including differences in patient background, the surgical technique performed, the time from surgery to follow up, and the definition of potency.8 Furthermore, inconsistent methods of assessment, specifically whether validated instruments are used or not, also influence the reported postoperative ED rate. Unfortunately, most of the studies used non-validated questionnaires or an open interview. Mulhall pointed out the minimal requirements for adequate reporting of postoperative EF outcomes. These include comorbidity profile, patient selection process, data acquisition methods, questionnaires used, baseline EF data, long-term EF data, definition of adequate EF, proportion of men returning to normal, proportion of men returning to preoperative EF level, and erectogenic medications use.9 LRP allows better exposure of the surgical site. The magnifying effect of optical endoscopy leads to excellent identification of structures, resulting in minimized damage to the striated sphincter and better preservation of neurovascular structures. Thus it has been considered that laparoscopy offers a significant improvement of postoperative rates of potency if nerve-sparing surgery is performed. So far, there have been no randomized trials directly studying the open and laparoscopic approaches. Several uncontrolled cohort studies performed in a non-randomized fashion could not demonstrate any advantage in favor of LRP compared to the open approach in regard to the potency preservation rate.7 At this time, LRP and retropubic radical prostatectomy (RRP) are probably equivalent in sexual function outcomes if experienced surgeons perform these procedures. Therefore, the factors affecting the preservation of EF in LRP are thought to be similar to those in RRP, including preoperative potency rate, patient age, and technical aspects of nerve-sparing procedures. The use of a phosphodiesterase type 5 inhibitor also results in improved postoperative potency. Recently, Hu et al. conducted a population-based observational cohort study using US Surveillance, Epidemiology, and End Results Medicare linked data.10 In their study of approximately 9000 prostate cancer cases treated surgically, 22% were treated with minimally invasive radical prostatectomy including LRP and robotic-assisted radical prostatectomy and were compared with RRP. Patients undergoing minimally invasive radical prostatectomy experienced earlier recovery from surgery and fewer perioperative complications, but also a significantly worsening potency preservation rate, compared to RRP. Although their study had limitations with respect to evaluating the ED rate after surgery, including the use of non-validated instruments for the assessment and no information concerning the nerve-sparing procedure performed, the reported result is impressive and surprising because patients as well as some physicians believed that the improved and technically advanced procedure for prostate cancer would provide better results, even for functional outcome. One reason why minimally invasive radical prostatectomy had a worse outcome for the postoperative potency-preserving rate might be associated with the slow learning curve for mastering the technical aspects of LRP. In conclusion, the accumulated evidence is still insufficient to answer the question of whether LRP could provide a better outcome for erectile recovery. Eiji Kikuchi md phd and Mototsugu Oya md phd Department of Urology, Keio University School of Medicine,Tokyo, Japan [email protected] The emergence of robotic surgery using the daVinci surgical system (Intuitive Surgical, Sunnyvale, CA) has revolutionized the surgical management of prostate cancer. Robotic systems allow an intuitive laparoscopic approach with 10–12× visual magnification and a 7° range of motion without unfavorable hand-shake. The introduction of an anatomical dissection to preserve the neurovascular bundles (NVB), as first described by Walsh et al., has been one of the most significant achievements in urological surgical procedures for prostate cancer. However, preservation of sexual function continues to be a formidable quality-of-life issue with this surgery and maximizing the preservation of sexual function remains as a controversial and challenging topic. Because factors other than the surgeon's volume or the approach of nerve sparing (NS) have a significant effect on the recovery of potency, including patient age and use of postoperative medications, potency is one of the most difficult outcomes to evaluate after radical prostatectomy (RP). In addition, the assessment of postoperative potency is still not standardized due to non-validated questionnaires as well as open interviews, especially in Japan. Reports on robot-assisted laparoscopic radical prostatectomy (RALP) have given weighted mean potency rates of 38.4%, 61.1%, 71.2% and 94% at 3, 6, 12 and >18 months after RP, respectively. Different studies have addressed the importance of surgical technique during dissection of the NVB for preserving potency after RALP. In a prospective non-randomized study, Finley et al. showed that the adoption of a cautery-free technique for dissecting the NVB allowed significantly higher potency rates after surgery.11 Likewise, Coughlin et al. recently described the benefit of an athermal early retrograde release of the NVB during RALP, hybridizing the traditional open anatomical approach with those of the laparoscopic antegrade approach.12 In terms of the relation of nerve volume and potency preservation, it has been reported to be 47–80% for unilateral NS and 63.8–100% for bilateral NS. Many authors have reported similar outcomes of potency preservation in spite of various efforts for improved NS techniques (either unilateral or bilateral), and now this concept seems to be a common belief. Ahlering et al. showed that preservation of just the unilateral nerve resulted in similar potency recovery to that with bilateral nerves preserved in the majority of patients. They suggested that crossover innervation of the one nerve is favored over compensation and warned that techniques that increase nerve volume in exchange for the risk of positive surgical margins may need careful introspection.13 This finding has also been reported by both open and laparoscopic surgeons. Whether there exists some difference in the potency rates after open, laparoscopic or robotic RP is still not defined. It has been proposed that RALP might prevent damage to the NVB, as the 3-D magnified vision offered by the daVinci Surgical System allows more precise dissection and prevents inadvertent incision, traction or incorporation of the NVB into a suture or a clip. Rocco et al. reported higher potency rates after RALP than after open RP at 3, 6 and 12 months (RALP 31%, 43% and 61%, respectively; open RP 18%, 31% and 41%, respectively; P = 0.006, 0.045 and 0.003, respectively). Similarly, Tewari et al. reported earlier recovery of potency after RALP than after open RP. Patients with RALP showed earlier return of erections (50% at a mean follow up of 180 days, vs 440 days after open RP) as well as quicker return to intercourse (50% at 340 days, vs 700 days after open RP) than patients who had undergone open RP. In contrast to these results, Krambeck et al. showed comparable potency rates between RALP and open RP at the 1-year follow-up examination (RALP 70.0%, open RP 62.8%, P = 0.081). Table 1 lists the outcomes of RALP with different techniques for potency recovery. The American Urological Association Guideline Panel found that postoperative erectile dysfunction (ED) rates have varied from 9% to 86%. To date, penile rehabilitation has shown promise in helping men who undergo RP for prostate cancer to recover erectile function after surgery. The concept of penile rehabilitation is based on the research findings that the loss of daily and nocturnal erections after RP leads to poor corporal oxygenation with penile atrophy, veno-occlusive dysfunction and smooth muscle apoptosis. Due to the fact that the cavernous tissue counteracts these processes through the release of the inducible isoform of nitric oxide synthase, phosphodiesterase type 5 inhibitors (PDE5i) have been the main focus of interest supporting penile rehabilitation after RP. Several multicenter randomized, double-blinded trials of PDE5i therapy after RP reported that administration of PDE5i soon after nerve-sparing surgery can improve the rate of return of normal, spontaneous erectile function compared to a placebo.19 Although men who choose RALP may represent a unique patient cohort for individual expectations for recovery and may also be more motivated to achieve potency, only a few studies have been conducted to assess the effect of PDE5i following RALP so far. According to this limited information, long-term compliance of PDE5i seems to be one of the independent predictors of potency return after RALP, however, the high cost of medication remains a significant barrier to maintaining this therapy.20 Needless to say, surgical technique during RP seems to have the greatest impact on preserving erectile function. It is still difficult to give general recommendations for the management of ED in men undergoing RP because of limitations in the available studies conducted. As well as difficulties in defining and documenting erectile function, a number of factors limit accurate evaluation, such as inconsistencies in study design, variations of patient populations, and patient compliance with therapy. More rigorous studies are needed to define the exact impact of penile rehabilitation for a contribution to ED treatment. Kunihiko Yoshioka md phd, Yoshihiro Nakagami md phd, Tadashi Hatano md phd, Choichirou Ozu md phd, Yutaka Horiguchi md phd, Kazunori Namiki md phd and Masaaki Tachibana md phd Department of Urology, Tokyo Medical University,Tokyo, Japan [email protected] External beam radiotherapy (EBRT) has been one of the standard treatments for organ-confined or locally advanced prostate cancer. Other radiation therapies (RT), such as brachytherapy and intensity-modulated radiation therapy (IMRT), are available and treatment-related adverse events have dramatically decreased. Moreover, androgen deprivation therapy during and after radiotherapy is another standard method for maximizing cancer control and disease-specific survival. Erectile dysfunction (ED) is a major late complication following EBRT. Occurrence rates of ED after EBRT vary from 36% to 59% according to prospective studies.21 ED rates also vary at different time-points, and EBRT-related ED increases gradually after the treatment. The reported ED rate was 27% after 1 year, and it increased to 36% after 2 years.21 The rationale for the gradual increase of ED following EBRT is the progressive vascular damage induced by radiation. Goldstein et al. reported a milestone study on patients treated with EBRT for prostate cancer.21 They demonstrated normal neurological examinations and abnormal penile Doppler images in all patients. A selective pudendal arteriography revealed occlusive vascular disease within the pelvic RT field. In the limited number of animal experimental studies on EBRT-related ED, one study clearly demonstrated changes in the arteries of the rat penis after fractionated irradiation of the prostatic area.22 Arteries developed loss of smooth muscle, intimal thickening, and occlusions after five daily fractions of 7.4 Gy. The data suggested that ED after RT is caused by radiation damage to the arterial supply of the corpora cavernosa. A strong relationship was suggested by Fisch et al. between ED and the dose-volume on the penile bulb. Mulhall et al. also concluded that patients who received 70 Gy or more than 70% of the bulb appeared to be at a very high risk of ED. Moreover, of the patients who could undergo cavernosography, 80% had a venous leak, most commonly from the crura, which could be induced by the fibrosis of cavernous tissue.21 Thus, the etiology of EBRT-related ED is fundamentally vasculogenic but complicated, which includes both arterial and veno-occlusive dysfunction. Minimizing the radiation dose to the cavernous tissue close to the prostate is essential to prevent vascular damage, and the more focused irradiation onto the prostate is crucial. It is reported that large doses of radiation are being delivered to erectile tissue in the proximal penis, despite careful pretreatment planning for three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer.21 In the recent IMRT study, the mean proximal cavernous tissue and bulb doses were reduced by 40 and 50% at 81 Gy compared with 3D-CRT. This resulted in improved potency rates over the outcomes observed with 3D-CRT.21 Phosphodiesterase type 5 inhibitors (PDE5i) are well known as being effective as treatment for EBRT-related ED. There is a clear time-dependence for the response to this therapy with a stepwise decrease, which is similar to EBRT-related ED occurrence.21 The response rates in men who underwent RT were about 80% at 1 year and 40% at 3 years, respectively. The time-dependent decrease of PDE5i efficacy is considered to be due to the aforementioned venous leakage via the fibrosis of cavernous tissue. In the recent EBRT strategy, androgen deprivation therapy is crucial, especially for high-risk and locally advanced prostate cancer. However, there is serious concern regarding its use in erectile function (EF), because androgen deprivation itself has a deteriorating effect. For patients with RT, the PDE5i response, mean EF and percent who experienced EF normalization at each time-point were lower in those with vs those without androgen deprivation.23 However, because patients with androgen deprivation have less sexual desire, their level of bother regarding ED might be low, and they might not seek ED treatment. Thus, sufficient informed consent is needed from patients treated with EBRT and androgen deprivation. Several predictors for EBRT-related ED were suggested, such as a baseline EF, age, comorbid status of hypertension and diabetes. Pinkawa et al. reported in their prospective study that preoperative EF is well-correlated with EF 1 year after EBRT.24 They reported that patient age and diabetes were similarly independent risk factors for EBRT-related ED. The predictors for PDE5i efficacy are also similar to EBRT-related ED: baseline EF and age.21 We have to make every effort to obtain the best knowledge at that time and to have sufficient discussions with patients individually. EBRT has been developed step-by-step to maximize efficacy and to minimize adverse effects: conventional RT, 3D-CRT, and IMRT. The recent novel technology for prostate cancer is stereotactic body radiotherapy. Although the protective effect for EF is still not so high (baseline ED rate was 38% and increased to 71% after treatment),25 it is a promising modality for the future. In conclusion, there is no treatment without any influence on EF among EBRT for prostate cancer so far. However, we will definitely see further improvement in the management of EBRT-related ED in the future. Shin-ichi Hisasue md phd Department of Urology, Sapporo Medical University, School of Medicine,Sapporo, Hokkaido, Japan [email protected] Since low-dose-rate brachytherapy (BT) using iodine-125 seed was legally approved in Japan in 2003, the number of patients who underwent BT has increased, and more than 13 000 Japanese patients received BT until 2009. The short hospital stay, less-invasive procedure, and well-preserved postoperative quality-of-life (QOL) are the main advantages encouraging many patients with low-risk prostate cancer to accept BT. The oncological outcome of definitive radiation therapy such as external beam radiation therapy (EBRT) and BT is similar to that of radical prostatectomy in patients with early prostate cancer. The QOL outcome after therapy is an important factor to make the most preferable choice among various therapeutic modalities.26 Regarding sexual function, the patients who received BT showed relatively well-preserved erectile function. According to the meta-analysis by Robinson et al.,27 the probability of retaining erectile function at 1 year after BT was 76% in patients with prostate cancer. BT showed the highest probability of erectile function among the various definitive therapies for localized prostate cancer. However, the preservation rate of erectile function decreased significantly with aging.28,29 It may be considered that age and pretreatment status of erectile function are the most important factors that influence erectile function following BT. The cause of radiation-induced erectile dysfunction (ED) should be considered as multi-factorial. Mechanical injury by needle punctures, radiation toxicity on the neurovascular bundle, excessive radiation dose to the penile bulb, patient age, smoking, diabetes mellitus, and psychological factors are considered as important risk factors. Although many investigators tried to find out the most influential factor, now the conclusion is still controversial. Many investigators have assessed radiation-induced ED in patients who have received BT. Merrick et al.28 concluded that post-BT ED was more frequent in their study using the International Index of Erectile Function-5 (IIEF5) questionnaire than in previous reports. When the potency of erectile function was defined as an IIEF5 score of 11 or greater, the actuarial 2-, 3- and 6-year potency-preservation rates were 47%, 40%, and 39%, respectively. A multivariate analysis revealed that the potency score before BT, use of supplemental EBRT, and diabetes mellitus were significant independent predictors of potency preservation following BT. Solan et al.29 reported that the actuarial 3-year potency-preservation rate was 77% when they defined the potency of erectile function as an IIEF5 score of 16 or greater and the Mount Sinai Erectile Function Score of 2 or greater (Table 2). Between July 2004 and May 2008 at Nara Medical University, 128 hormonal-therapy-naïve patients underwent BT with or without supplemental EBRT. Fifty-seven patients (44%) had an IIEF5 score of 11 or greater (Group 1) and 38 patients (30%) had an IIEF5 score of 16 or greater (Group 2) before BT. The changes of IIEF5 scores after BT were assessed in 54 Group 1 patients and in 37 Group 2 patients. The mean ages of the two patient groups at BT were 65 and 64 years, respectively, and the median follow-up period was 24 months in both patient groups. In Group 1, the actuarial 1-, 2-, and 3-year preservation rates of erectile function were 50%, 41%, and 28%, respectively. In Group 2, the corresponding rates of erectile function were 46%, 39%, and 34%, respectively (Table 2). Our data showed that the preservation rate of erectile function of the Japanese patients was nearly equal to or less than that of the previously reported American patients. Interestingly, Namiki et al.30 found that the Japanese men with clinically-localized prostate cancer had poorer sexual function than the American men. Nevertheless, Japanese men seem not to be seriously bothered by deterioration of their sexual function. Similarly to our recent study,31 the sexual function score of the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) of the Japanese patients remarkably declined from 1 through 12 months after BT, whereas the sexual bother score of the UCLA-PCI showed no significant change. The subgroup analysis using a cut-off score of 17 revealed that the lower IIEF5 patient group (IIEF5 score of less than 17) and the higher IIEF5 patient groups (IIEF5 score of 17 or more) before BT showed a significant decrease in the IIEF5 score at 12 months after BT. On the other hand, the sexual function score of the UCLA-PCI in the higher IIEF5 patients significantly decreased from 1 to 12 months after BT, while the lower IIEF5 patients showed no significant change during 12 months after BT. The sexual bother score of both groups showed no significant change during the 12 months after BT. Taken together, although sexual function following BT deteriorates gradually and is likely to worsen significantly year by year, patients seem to be minimally bothered during follow up after BT. Sexual function after BT may depend not only on the degree of radiation-induced damage but also on the age and erectile potency before BT. It is well known that patients with radiation-induced ED highly respond to a potency aid such as phosphodiesterase type 5 inhibitors (PDE5i). Merrick et al.28 reported that 62 patients with BT-induced ED used sildenafil citrate after BT, and that 53 patients (85%) showed a favorable response. The response to sildenafil after BT significantly correlated with the potency score before BT. Therefore, a certain population of patients who choose BT in order to retain their sexual function should use PDE5i. In conclusion, the overall sexual function in patients who receive BT is preferentially preserved, while the chronological deterioration of sexual function is remarkably noticed in the long-term follow up after BT. Importantly, Japanese patients are usually not bothered by deterioration of their sexual function after BT. In a given younger-elderly patient with active sexual function who desires to preserve erectile function after BT, use of PDE5i should be taken into consideration at an early stage after treatment. Nobumichi Tanaka md phd1 and Isao Asakawa md phd2 Departments of 1 Urology and 2 Radiation Oncology, Nara Medical University,Kashihara, Japan [email protected] Androgen deprivation therapy (ADT) is the standard initial treatment for advanced prostate cancer. The concept of androgen deprivation for prostate cancer was first introduced in 1941 by Huggins and Hodges. They showed the beneficial effects of castration and estrogens administration in patients with metastatic prostate cancer. Since then, various approaches to reduce androgen activity have been introduced, such as bilateral orchiectomy or administration of estrogenic compounds. More recently, medical castration has been applied in the form of luteinizing hormone-releasing hormone (LHRH) analogues and in conjunction with androgen blockade by anti-androgens. Various adverse events of ADT have been reported such as loss of libido, hot flush, osteoporosis, erectile dysfunction (ED), anemia, depression, fatigue, gynecomastia, diabetes mellitus, metabolic syndrome, and altered body composition. Despite repeated reports of these adverse events of ADT, there is indeed little information about the incidence of sexual problems including loss of libido and ED, particularly the response to ED-targeted therapy. Patients with prostate cancer may suffer from ED just after surgical treatment, but they gradually recover their erectile function, especially the patients who undergo the bilateral nerve-sparing procedure or who have early rehabilitation by taking a phosphodiesterase type 5 inhibitor (PDE5i). On the contrary, the patients who undergo radiation therapy may maintain their erectile function for a while after initiation of the treatment, but they may gradually lose this function in the long run. For patients who undergo ADT, they may have impaired erectile function after initiation of the therapy, and their suffering lasts until termination of ADT. They may also suffer from a decrease in libido much more than patients undergoing surgery or radiation therapy because of the diminished circulating testosterone level. Regarding the medications that may cause ED, the Japanese Society for Sexual Medicine (JSSM) reported that anti-androgen (chlormadinone acetate) and LHRH analogue (leuprorelin) have moderate effects on the degree and frequency of causality of ED.32 The Prostate Cancer Outcomes Study of the Surveillance, Epidemiology, and End Results program examined the quality-of-life outcomes of 431 men with various stages of prostate cancer who received ADT and no other treatment within one year of the initial diagnosis.33 In this study, men reporting no sexual interest increased from 27.6% to 63.6% after orchiectomy and from 31.7% to 58.0% after gonadotropin-releasing hormone (GnRH) agonist. Regarding sexual function, the authors reported that men without sexual activity increased from 47.9% to 82.8% after orchiectomy and from 45.0% to 80.2% after GnRH agonist. Moreover, among the men with some interest in sex before treatment, 51% reported “no interest” after therapy. Approximately 73% of men ceased engaging in sexual activity after treatment, and 69% of men who were potent before treatment lost their potency after treatment, and no differences were observed between the types of ADT therapy. In another study, 91% of men were found to have ED after ADT. The Prostate Cancer Outcomes Study analyzed the treatment harms and patient satisfaction, and indicated that the inability to have an erection was higher in men undergoing active intervention, especially ADT (86%) or radical prostatectomy (58%), than in men undergoing watchful waiting (33%).34 In Japan, Marumo et al. reported that the patients who underwent ADT for prostate cancer also demonstrated reduction in serum testosterone concentrations with consequent suppression of sexual desire, sexual interest, and sexual intercourse, as well as significant reduction in the frequency, magnitude, duration, and rigidity of nocturnal penile tumescence. This study clearly demonstrates that testosterone concentration strongly correlates with erectile function, sexual interest, and activity.35 In a more recent study on 395 men undergoing ADT for prostate cancer with a mean follow up of 87.4 months, 57 (14.4%) reported ED after ADT and received target therapy. Of these, 40 (70%) had new-onset ED after ADT induction, while 17 (30%) reported ED before ADT induction. Despite the initiation of ADT and reduction in testosterone production, the success rates were 47% and 44% for combined ED therapy and PDE5i monotherapy, respectively.36 Multivariate analysis revealed that age < 70 years (odds ratio: 3.75, P < 0.001) and the absence of diabetes mellitus (odds ratio: 3.89, P = 0.024) significantly correlated with a higher probability of having ED after ADT when adjusting for other variables, such as body mass index, serum prostate-specific antigen level before ADT, race, and the method of ADT. Unfortunately, this study was retrospective and non-randomized, and therefore the evidence is still insufficient to conduct appropriate management of ED after ADT. In conclusion, post-ADT ED is reportedly very common, but because of the paucity of clinically important information derived from high-quality randomized trials, further investigation is required to find an accurate answer for the appropriate management of ED after ADT. Jintetsu Soh md phd Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine,Kyoto, Japan [email protected]
Search from 250 M+ research papersSearch from 250 M+ research papers
Mar 1, 2024
Kitty Y. Wu + 5
Open Access