Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Regret in men treated for localized prostate cancer

PURPOSE: We identify the predictors of medical regret in men treated for localized prostate cancer. MATERIALS AND METHODS: Patients previously treated for early stage prostate cancer were assessed for treatment regret using validated items. Univariate and multivariate analyses identified associations between regret and demographic characteristics, clinical outcomes, medical knowledge, and general and disease specific health related quality of life as measured by the general health perceptions domain of the RAND 36-Item Health Survey and a validated short form of the University of California, Los Angeles Prostate Cancer Index. RESULTS: Of 96 respondents (mean age 64 years, mean followup 2.8 years) 16% expressed regret with treatment decisions. Regretful men were almost twice as likely as nonregretful men to have less than a college education (60% versus 33%, p = 0.05) and worse current health related quality of life (p <0.05). In addition, regretful men tended to be unable to recall the most recent prostate specific antigen accurately (p = 0.06). Men with and without regret did not differ in other demographic characteristics, treatment choice or clinical outcomes. Regretful men were more likely to say they would choose a different treatment if they could. In multivariate analyses worse quality of life predicted regret but decline in quality of life with time was not associated with regret. CONCLUSIONS: Men expressing regret over treatment choice for localized prostate cancer have poorer health related quality of life. Further study is needed to identify factors that predict posttreatment regret. Such information will allow patients and physicians to individualize treatment decisions, optimize quality of life and avoid medical regret.     

Treatment of erectile dysfunction following therapy for clinically localized prostate cancer: patient reported use and outcomes from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study

PURPOSE: Erectile dysfunction (ED) persists for years following curative therapies for clinically localized prostate cancer. We report use and treatment outcomes in a 5-year interval in a population based cohort from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study. MATERIALS AND METHODS: A sample of 1,977 men with localized prostate cancer who received external beam radiation therapy or radical prostatectomy in 1994 to 1995 were surveyed for 5 outcome measures of ED treatment, namely treatment, perceived helpfulness, erectile sufficiency, sexual activity frequency and erection maintenance. Subjects were surveyed 6, 12, 24 and 60 months after prostate cancer diagnosis. RESULTS: Overall 50.5% of men ever used ED treatment. The use of ED treatments increased during the study course. Subject age, regular sexual partner and baseline sexual activity were factors positively associated with ED treatments. While it was used uncommonly (1.9%), a penile prosthesis was perceived as the most helpful ED treatment (helped a lot in 52% of respondents). Sildenafil helped a lot in 12% of respondents. Erectile fullness, erection maintenance and sexual activity frequency were modestly improved in men using ED treatment compared with those in men not using ED treatment. CONCLUSIONS: Approximately half of the patients in this population based cohort of men used ED treatment during the 5 years following prostate cancer diagnosis. Men using ED treatments had modest improvement in sexual function compared with men that in who did not receive ED treatment at 60 months. More effective treatments for ED following local therapy for prostate cancer are needed.     

Osteoporosis in men treated with androgen deprivation therapy for prostate cancer

PURPOSE: We surveyed the growing literature on osteoporosis secondary to androgen deprivation therapy and provide suggestions regarding its identification and treatment. MATERIALS AND METHODS: We reviewed pertinent studies of male osteoporosis, osteoporotic fracture incidence or bone mineral density loss as a possible side effect of prostate cancer treatment and potential therapies for this side effect. RESULTS: Hypogonadism is a well-known cause of secondary osteoporosis in men. There is evidence of decreased bone mineral density with all types of androgen deprivation therapy, presumably due to its anti-testosterone effect. Bone mineral density loss is 3% to 5% yearly in the first few years of androgen deprivation therapy with an increase in osteoporotic fracture incidence. There are little data on potential treatments, although bisphosphonates and intermittent androgen deprivation therapy may have salutary effects. CONCLUSIONS: Osteoporosis is an important and debilitating side effect of androgen deprivation therapy, although precise estimates of its incidence, degree and cost are not completely elucidated. Until more data are available, it is prudent for all men beginning androgen deprivation therapy to receive calcium and vitamin D, and maintain a moderate exercise regimen. Baseline and at least 1 followup bone density measurement seem appropriate with bisphosphonate treatment a possibility in those in whom osteoporosis develops. More research is needed to explore the effect of bisphosphonates, calcium and vitamin D supplementation, exercise, calcitonin, selective estrogen re-uptake inhibitors, estrogens and intermittent androgen deprivation therapy on the course of androgen deprivation therapy induced osteoporosis. The osteoporotic fracture incidence and bone mineral density should be regularly incorporated into studies involving the hormonal treatment of prostate cancer.     

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.     

Hyperbaric oxygen therapy for radiation induced proctopathy in men treated for prostate cancer

PURPOSE: Radiation proctitis is a common complication following external beam radiation therapy and brachytherapy for prostate cancer. While 95% percent of radiation induced proctitis is temporary and self-limiting, up to 5% of patients experience toxicities that are refractory to conservative management. Hyperbaric oxygen has a well-defined role in treating chronic wounds, osteomyelitis, hemorrhagic cystitis and necrotizing fasciitis. We reviewed our experience with hyperbaric oxygen therapy for radiation induced proctitis in patients undergoing radiation treatment for prostate cancer. MATERIALS AND METHODS: From October 1998 to December 2003, 27 patients with radiation induced proctitis secondary to brachytherapy (4), external beam radiation therapy (16) or combined modality (7) for prostate cancer were treated with hyperbaric oxygen therapy at Virginia Mason Medical Center in Seattle, Washington. In all patients primary medical or endoscopic management had failed. Patients received 100% oxygen in a multiplace hyperbaric chamber at a pressure of 2.4 atmospheres absolute for 90 minutes 5 to 7 days weekly for an average of 36 sessions (range 29 to 60). Data were collected from a retrospective review of medical records following approval by the Institutional Review Board at Virginia Mason Medical Center. RESULTS: All 27 men completed the planned course of therapy. Of patients with bleeding 48% showed complete resolution after therapy, while 28% reported significantly fewer bleeding episodes. Of patients 50% noted complete resolution of fecal urgency. Six of the 8 patients (75%) with pain noticed some improvement after therapy, although no patients reported complete resolution of rectal pain. Of patients with rectal ulceration 21% showed complete resolution of the ulcer on posttreatment endoscopy, while 29% showed evidence of improvement. Six patients (43%) had no change or worsening of rectal ulcers. Overall 67% of patients had a partial to good response, while 33% showed no response or disease progression. CONCLUSIONS: This series of patients showed a good overall response rate to hyperbaric oxygen for radiation induced proctopathy after other attempts at management had failed. Hyperbaric oxygen is generally well tolerated and it remains an important treatment option for managing this common and difficult disease.     

The patient's dilemma: prostate cancer treatment choices

PURPOSE: We summarize the literature addressing factors that influence treatment decisions made by men with prostate cancer. MATERIALS AND METHODS: A MEDLINE search of the English language literature published between 1969 and 2000, using the combined MESH key words "prostatic neoplasms," "patient participation," "Internet" and "decision making," generated 181 abstracts. Only 23 of these publications addressed factors influencing treatment decisions made by men with prostate cancer. Nine additional relevant studies were identified from references in the original 23 articles. Subsequently a search for the term "prostate cancer" using several popular Internet search engines yielded more than 1 million hits. A further search was performed using the key words "prostate cancer" and "prostate" within on-line archives of the United Kingdom television channels BBC, ITV, and channels 4 and 5, and newspapers The Sun, The Daily Mail, The Observer, The Guardian and The Times. RESULTS: When there is poor quality evidence or little professional consensus to support a particular treatment over another, no clinical guidelines regarding treatment are possible. Patients are faced with a series of options, and the data reveal that the process of choosing between these options is based on input from a large number of sources. These sources differ in the way that benefits of treatment are emphasized over harms and vice versa. We identified little evidence regarding which type of input exerts the greatest influence on patients. It may be that the sources associated with the most bias have the greatest influence. CONCLUSIONS: There is a paucity of information on how patients with prostate cancer use different types of input in the treatment decision making process. The physician, as principal caregiver, still appears to have the most direct influence on patient choice. Just how long this status will continue is uncertain.     

Ejaculatory disorders may affect screening for prostate cancer

PURPOSE: Ejaculatory disorders will be experienced in most men who are treated for localized prostate cancer. Baseline rates of ejaculatory disorders are unknown in men at risk for prostate cancer. Therefore, we explored the prevalence of those disorders and associated bother in men without evidence of prostate cancer who participated in an annual prostate cancer screening event. MATERIALS AND METHODS: A cohort of 1,273 men without clinical evidence of prostate cancer completed the self-administered Danish Prostate Symptom Score for sexual dysfunction. This questionnaire quantifies the rate of reduced ejaculatory volume, ejaculatory pain and the rate of coexistent erectile dysfunction. RESULTS: Mean age was 57.6 years (range 40 to 89). Of all men 46% (563) had reduced ejaculatory volume and 66% (356) of affected men were bothered by this condition. Ejaculatory pain was reported in 11% (134) and 89% (118) of these men reported associated bother. Finally, 45% (554) reported erectile dysfunction and 73% (403) reported associated bother. Reduced ejaculatory volume was associated with erectile dysfunction (p<0.001) and advanced age (p<0.001). Ejaculatory pain was not associated with one of these variables. CONCLUSIONS: Virtually all men will be affected by ejaculatory disorders after definitive treatment for localized prostate cancer. Therefore, it is important to observe that half of these individuals already have underlying reduced ejaculatory volume before treatment. Moreover, 1 of 10 men will be affected by ejaculatory pain. Both disorders are a significant source of bother and should be considered when treatment related quality of life is assessed.     

Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial

PURPOSE: We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP). MATERIALS AND METHODS: This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater "yes" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion. RESULTS: Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p <0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all randomized patients who received 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. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events. CONCLUSIONS: Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.     

Incidence of erectile dysfunction in Italian men with diabetes

PURPOSE: We determined the incidence of erectile dysfunction in Italian men with diabetes. MATERIALS AND METHODS: We estimated the incidence of erectile dysfunction, defined as failure to achieve and maintain erection sufficient for satisfactory sexual performance, after 2.8 years of followup in 1,010 men enrolled for a prevalence study of erectile dysfunction in diabetes. RESULTS: Of the 1,010 men 192 (19%) complained of erectile dysfunction. The crude incidence rate of erectile dysfunction was 68 cases per 1,000 person-years (95% confidence interval 59 to 77). The incidence of erectile dysfunction increased with increasing age (10-fold higher for ages 70 to 79 than for 19 to 29 years), duration of diabetes (1.6-fold higher a history of 11 years or greater than for less than 5) and deteriorating metabolic control (1.7-fold higher for hemoglobin A1c greater than 9% than less than 7.5%). Moreover, it was higher in type 2 than in type 1 diabetes (74 versus 45 cases per 1,000 person-years). The relative risk was 1.75, 2.02, 1.97, 1.16, 1.86, 3.79 and 1.52 for associated obliterative arterial disease of the lower legs, ischemic heart disease, renal disease, autonomic neuropathy, sensitive and motor neuropathy, diabetic foot and retinal disease, respectively. Of the characteristics at study enrollment patient age, duration of diabetes, renal disease and hypertension were multivariate predictors of the erectile dysfunction 2.8 years later. CONCLUSIONS: The incidence of erectile dysfunction in Italian men with diabetes at a mean followup of 2.8 years was 68 cases per 1,000 person-years, more than 2-fold that in the Massachusetts Male Aging Study of the general population. The knowledge of this incidence should promote specific preventive and therapeutic interventions for erectile dysfunction in men with diabetes.     

A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer

PURPOSE: Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer. We performed a prospective study which measured penile length before and after radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon. Repeat measurements were performed at 3-month intervals following surgery. Penile measurements (cm.) consisted of flaccid length, stretched length, depth of prepubic fat pad and circumference. Statistical analysis of penile measurements was performed using the paired samples and independent Student's t test, Pearson's correlation and analysis of variance. RESULTS: Mean patient age was 59.1 (range 42 to 76). No patient had a penile abnormality, for example Peyronie's disease, or history of penile or urethral surgery. The size of the penis was significantly smaller after prostatectomy, and there was a significant difference for flaccid (p <0.001), stretched (p <0.001), prepubic fat pad (p = 0.02) and circumference measurements (p <0.01). Twelve patients (19%) had a 15% or greater decrease in stretched penile length. When dichotomizing groups at the cut point of 15% decrease, the independent t test of prostate size was not significant (t[df 36.7] = -1.83, p = 0.076). Nerve sparing was not significant in relation to change in penile stretched length, (F[df 2, 62] = 0.501, p = 0.609). CONCLUSIONS: Our findings support observations of decreased penile length after radical prostatectomy. Men should be counseled before radical prostatectomy that penile shortening may occur.     

Incidence and management of gynecomastia in men treated for prostate cancer

PURPOSE: Gynecomastia is a potentially treatment limiting adverse event in men receiving hormone therapy for prostate cancer. MATERIALS AND METHODS: In large, randomized, placebo controlled studies approximately 50% or more of patients with prostate cancer experienced gynecomastia due to multiple mechanisms. Although its severity was mostly reported as mild to moderate, gynecomastia was cited as the reason for most premature withdrawals from therapy. In patients with advanced forms of prostate cancer bilateral orchiectomy was associated with the lowest incidence of gynecomastia, followed by nonsteroidal antiandrogen therapy, diethylstilbestrol and estrogen in rank order. RESULTS: It is important that gynecomastia is well managed in patients with prostate cancer who want to proceed with hormone therapy. Patients should be assessed for the likely etiology of gynecomastia and preventive therapy or treatment for established gynecomastia should be instituted. Prophylactic radiotherapy has been shown to decrease the incidence of hormone induced gynecomastia by more than 50%. An alternative course of action, which may be more convenient for the patient, is the prophylactic use of tamoxifen. Tamoxifen may also mitigate or resolve gynecomastia during its early or proliferative phase. In severe long-standing gynecomastia surgery is warranted since medical therapies are less likely to succeed. Aromatase inhibitors and 4-hydroxytamoxifen are investigational. CONCLUSIONS: Gynecomastia is a significant problem in men undergoing hormonal therapy for prostate cancer. It requires prompt recognition, evaluation and management.     

The prevalence of erectile dysfunction among Brazilian men screened for prostate cancer

OBJECTIVE

To determine the prevalence of erectile dysfunction (ED) in a large cohort of Brazilian men who were screened for prostate cancer, and to determine risk factors in this population, as there are large cultural differences among countries in reporting the frequency of ED, and it is likely that the prevalence of ED among men screened for prostate cancer cannot be generally applied across countries.

SUBJECTS AND METHODS

The analysis focused on the baseline characteristics of 1008 consecutive South American men from Brazil with no known prostate disease who had routine screening for prostate cancer by urologists. The variables analysed were patient age, urinary symptoms, patient health‐related quality of life (HRQL), prostate‐specific antigen (PSA) levels, prostate volume and erectile function. To assess lower urinary tract symptoms (LUTS) and HRQL, we used the American Urological Association symptom score and its appended eighth question, respectively. Benign prostatic hyperplasia was defined as a prostate volume of >30 g. Sexual function was assessed using the five‐item version of the International Index of Erectile Function questionnaire. Thus, ED was considered to absent for scores of 22–25, mild for 17–21, mild to moderate for 12–16, moderate for 8–11, or severe for 5–7. Obesity was defined by calculating the body mass index (BMI), and categorized as underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²) or obese (= 30 kg/m²). The mean (sd ) PSA level was 4.3 (6.7) ng/mL and the mean prostate volume 37.8 (21.8) mL. The correlation of ED with these variables was estimated using unconditional logistic regression models.

RESULTS

Information about erectile function was available for 908 patients. ED was considered to be absent, mild, mild to moderate, moderate and severe in 169 (18.6%), 210 (23.1%), 169 (18.6%), 138 (15.2%) and 222 (24.5%) patients, respectively. The ED was severe in 18.4%, 25.7% and 43.4% of patients with mild, moderate and severe LUTS, respectively (P < 0.001). The answer to the HRQL question was also significantly associated with ED; ED was severe in 16.5% of patients feeling delighted/pleased and in 35.8% of patients feeling unhappy/terrible (P < 0.001). The prostate volume was significantly related to ED. The BMI category showed that normal weight, overweight and obese patients had similar rates of ED (P = 0.415); ED was severe in about a quarter of the patients in each of these categories, and 50% and 24% of patients in the underweight and greater BMI groups had severe ED, respectively.

CONCLUSIONS

Of men screened for prostate cancer in Brazil, ≈40% have moderate or severe ED. Severe LUTS, higher HRQL scores, a large prostate volume, a low BMI and higher PSA levels might be associated with higher rates of ED. These variables should be considered when analysing the erectile function of patients screened for prostate cancer.     

Penile length changes in men treated with androgen suppression plus radiation therapy for local or locally advanced prostate cancer

PURPOSE: We determined penile length alterations in men treated with androgen suppression plus radiation therapy for local or locally advanced prostate cancer. MATERIALS AND METHODS: From November 2000 to November 2005, 47 patients were enrolled in this prospective study. After clinical staging all patients received hormonal therapy (luteinizing hormone releasing agonist, leuprolide acetate or goserelin every 3 months for a total of 3 injections) and at month 7 of hormonal therapy radiation therapy was begun (total 70 Gy) for 7 weeks. Stretched penile length measurements were performed before starting androgen suppression therapy and every 3 months thereafter with a paper ruler. RESULTS: With the initiation of therapy a gradual decrease in stretched penile length was observed. Penile shortening was statistically significant at a mean followup of 18 months (mean 14.2 to 8.6 cm, p <0.001). CONCLUSIONS: Our findings support observations of decreased penile length after neoadjuvant hormonal therapy plus external beam radiation therapy for local or locally advanced prostate cancer. Patients should be counseled before therapy that penile shortening may occur.