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PURPOSE - To assess whether BIO 300, a synthetic genistein nanosuspension, improves the therapeutic index in prostate cancer treatment by preventing radiation-induced erectile dysfunction (ED) without reducing tumor radiosensitivity.
METHODS AND MATERIALS - Male Sprague-Dawley rats were exposed to 25 Gy of 220-kV prostate-confined x-rays. Animals were randomized to receive sham radiation therapy (RT), RT alone, RT with daily BIO 300 at 2 experimental dosing regimens, or RT with daily genistein. Erectile response was evaluated over time. Penile shaft tissue was harvested for histologic analyses. Murine xenograft studies using prostate cancer cell lines determined the effects of BIO 300 dosing on RT efficacy.
RESULTS - Prostate-confined RT significantly decreased apomorphine-induced erectile response (P < .05 vs sham RT). Erection frequency in animals receiving prophylactic treatment with BIO 300 starting 3 days before RT was similar to sham controls after RT. Treatment with synthetic genistein did not mitigate loss in erectile frequency. At week 14, post-RT treatment with BIO 300 resulted in significantly higher quality of erectile function compared with both the RT arm and the RT arm receiving genistein starting 3 days before irradiation (P < .05). In hormone-sensitive and insensitive prostate tumor-bearing mice, BIO 300 administration did not negatively affect radiation-induced tumor growth delay.
CONCLUSIONS - BIO 300 prevents radiation-induced ED, measured by erection frequency, erectile function, and erection quality, when administered 3 days before RT and continued daily for up to 14 weeks. Data also suggest that BIO 300 administered starting 2 hours after RT mitigates radiation-induced ED. Data provide strong nonclinical evidence to support clinical translation of BIO 300 for mitigation of ED while maintaining treatment response to RT.
Copyright © 2019. Published by Elsevier Inc.
PURPOSE/OBJECTIVES - Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established. The cavernous nerves (CN) are postganglionic parasympathetic nerves located beside the prostate gland that assist in penile erection. This study was designed to investigate the role of CN injury, tissue damage, and altered signaling pathways in an RiED rat model.
METHODS AND MATERIALS - Male rats were exposed to a single dose of 25 Gy prostate-confined RT. Erectile function was evaluated by intracavernous pressure (ICP) measurements conducted both 9 and 14 weeks after RT. Neuronal injury was evaluated in the CN using quantitative polymerase chain reaction, conduction studies, transmission electron microscopy, and immunoblotting. Masson trichrome staining was performed to elucidate fibrosis level in penile tissues.
RESULTS - There were significant alterations in the ICP (P<.0001) of RT rats versus non-RT rats. TEM analysis showed decreased myelination, increased microvascular damage, and progressive axonal atrophy of the CN fibers after RT. Electrophysiologic analysis showed significant impairment of the CN conduction velocity after RT. RT also significantly increased RhoA/Rho-associated protein kinase 1 (ROCK1) mRNA and protein expression. In addition, penile tissue showed increased apoptosis and fibrosis 14 weeks after RT.
CONCLUSIONS - RT-induced CN injury may contribute to RiED; this is therefore a rationale for developing novel therapeutic strategies to mitigate CN and tissue damage. Moreover, further investigation of the RhoA/ROCK pathway's role in mitigating RiED is necessary.
Copyright © 2017 Elsevier Inc. All rights reserved.
Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.
BACKGROUND - The authors investigated the prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction in a contemporary, population-based prostate cancer cohort. They also explored the associations between baseline function and age, comorbidity, and timing of baseline survey completion with respect to treatment.
METHODS - The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a population-based, prospective cohort study that enrolled 3691 men with incident prostate cancer during 2011 and 2012. Pretreatment function was ascertained using the Expanded Prostate Cancer Index-26 (EPIC-26). Data were stratified by age, comorbidity, and timing of baseline survey completion with respect to treatment. Unadjusted and multivariable linear regression analyses were performed to evaluate the relations between exposures and pretreatment function.
RESULTS - After applying exclusion criteria, the study cohort comprised 3072 men. A strikingly high proportion of men reported inability to obtain erections satisfactory for intercourse (45%) and some degree of urinary incontinence (17%) at baseline. Sexual function was particularly age-sensitive, with patients aged ≤60 years reporting summary scores in excess of 30 points higher than patients aged ≥75 years (P < .001). Compared with the healthiest men, highly comorbid patients reported less favorable function in each domain, including urinary incontinence (summary score, 89.5 vs 74.1; P < .001) and sexual function (summary score, 70.8 vs 32.9; P < .001). Although statistically significant differences in summary scores were identified between patients who completed the baseline questionnaire before treatment (52%) versus after treatment (48%), the absolute differences were small (range, 1-3 points).
CONCLUSIONS - Patients with newly diagnosed prostate cancer exhibit a wide distribution of pretreatment function. The current data may be used to redefine the population "at risk" for treatment-related harms.
© 2014 American Cancer Society.
BACKGROUND - The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy.
METHODS - The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis. We used multivariable propensity scoring to compare functional outcomes according to treatment.
RESULTS - Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years.
CONCLUSIONS - At 15 years, no significant relative differences in disease-specific functional outcomes were observed among men undergoing prostatectomy or radiotherapy. Nonetheless, men treated for localized prostate cancer commonly had declines in all functional domains during 15 years of follow-up. (Funded by the National Cancer Institute.).
PURPOSE - We determined whether intensive glycemic therapy reduces the risk of erectile dysfunction in men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial.
MATERIALS AND METHODS - The Diabetes Control and Complications Trial randomized 761 men with type 1 diabetes to intensive or conventional glycemic therapy at 28 sites between 1983 and 1989, of whom 366 had diabetes for 1 to 5 years and no microvascular complications (primary prevention cohort), and 395 had diabetes for 1 to 15 years with nonproliferative retinopathy or microalbuminuria (secondary intervention cohort). Subjects were treated until 1993, and followed in the Epidemiology of Diabetes Interventions and Complications study. In 2003 we conducted an ancillary study using a validated assessment of erectile dysfunction in 571 men (80% participation rate), 291 in the primary cohort and 280 in the secondary cohort.
RESULTS - Of the participants 23% reported erectile dysfunction. The prevalence was significantly lower in the intensive vs conventional treatment group in the secondary cohort (12.8% vs 30.8%, p = 0.001) but not in the primary cohort (17% vs 20.3%, p = 0.49). The risk of erectile dysfunction in primary and secondary cohorts was directly associated with mean HbA1c during the Diabetes Control and Complications Trial, and Epidemiology of Diabetes Interventions and Complications combined. Age, peripheral neuropathy and lower urinary tract symptoms were other risk factors.
CONCLUSIONS - A period of intensive therapy significantly reduced the prevalence of erectile dysfunction 10 years later among those men in the secondary intervention cohort but not in the primary prevention cohort. Higher HbA1c was significantly associated with risk in both cohorts. These findings provide further support for early implementation of intensive insulin therapy in young men with type 1 diabetes.
Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
INTRODUCTION - Inflatable penile prostheses (IPPs) are a well-established and reliable treatment for medication refractory erectile dysfunction. The most serious complication with IPPs is infection, with the reported incidence after primary placement 1% to 3% and after revision surgery 8% to 18%.
AIM - The aim of this report is to describe an infected decommissioned IPP reservoir with Actinomyces neuii with successful preservation of a functioning implant.
METHODS - After 9 years of successful use with an IPP (AMS 700 CX) for Peyronie's disease and organic erectile dysfunction, a 79-year-old man underwent replacement with an AMS 700 LGX. The decommissioned reservoir was kept in the right prevesical space, and the new reservoir was placed in the left prevesical space. Three months later, he presented with right inguinal pain and swelling.
RESULTS - He was found to have an infected right reservoir with A. neuii, sparing his new IPP. After removal of the right reservoir, he had an uneventful recovery and has shown no evidence of infection in the new device.
CONCLUSION - Revision surgery for IPPs carries a higher risk for implant infection. This is the first report of a genitourinary implant infection with A. neuii. Aggressive surgical and medical treatment may allow preservation of the functioning implant, despite gross infection of the decommissioned reservoir.
© 2010 International Society for Sexual Medicine.
Treatment choices for metastatic prostate cancer are complex and can involve men balancing survival versus quality of life. The present study aims to elicit patient preferences with respect to the attributes of treatments for metastatic prostate cancer through a discrete choice experiment (DCE) questionnaire. Men with recently diagnosed localized prostate cancer were asked to envisage that they had metastatic disease when completing a survey. As expected, men with prostate cancer placed considerable importance on gains in survival; however, avoiding side effects of treatment was also clearly important. Survival gains should be considered alongside side effects when discussing treatment options in metastatic disease.
INTRODUCTION - The direction of the relationship between psychological adjustment and erectile dysfunction (ED) is unclear and may differ for different men, and few studies have examined psychological outcomes for men receiving ED treatment.
AIM - This study assessed the impact of ED therapy at baseline and 12-month follow-up, using standard psychological measures.
METHODS - Using an observational ED registry, we collected clinical and psychosocial data at baseline and 3, 6, and 12 months. Participants had (i) a patient-reported outcomes questionnaire at baseline and at least one follow-up; and (ii) data about ED treatments received during the study. Treated men were classified as responders based on improvements in International Index of Erectile Function scores from baseline to 12 months.
MAIN OUTCOME MEASURES - The main outcome measures were changes in psychological outcomes in relation to treatment status and baseline ED severity.
RESULTS - Of 153 patients, 40 responded to treatment, 49 did not respond to treatment, and 64 did not receive treatment. Treatment responders reported significant improvements in 12-month sexual self-efficacy but only small improvements or no change across five other psychological domains, whereas nonresponders reported small decrements. There was a trend for differences in sexual self-efficacy to vary by baseline ED severity, as well as by treatment response.
CONCLUSIONS - Diagnosing and successfully treating ED significantly affects patient psychological adjustment, so providers should actively diagnose and treat ED.