Life In Prostate Cancer Survivors Research Articles

Neighborhood greenness and long-term physical and psychosocial quality of life among prostate cancer survivors in the Health Professionals Follow-up Study

IntroductionNeighborhood greenness may benefit long-term prostate cancer survivorship by promoting physical activity and social integration, and reducing stress and exposure to air pollution, noise, and extreme temperatures. We examined associations of neighborhood greenness and long-term physical and psychosocial quality of life in prostate cancer survivors in the Health Professionals Follow-up Study. MethodsWe included 1437 individuals diagnosed with non-metastatic prostate cancer between 2008 and 2016 across the United States. Neighborhood greenness within a 1230m buffer of each individual's mailing address was measured using the Landsat satellite image-based Normalized Difference Vegetation Index (NDVI). We fit generalized linear mixed effect models to assess associations of greenness (in quintiles) with longitudinal patient reported outcome measures on prostate cancer-specific physical and psychosocial quality of life, adjusting for time-varying individual- and neighborhood-level demographic factors and clinical factors. ResultsThe greatest symptom burden was in the sexual domain. More than half of survivors reported good memory function and the lack of depressive signs at diagnosis. In fully adjusted models, cumulative average greenness since diagnosis was associated with fewer vitality/hormonal symptoms (highest quintile, Q5, vs lowest quintile, Q1: mean difference: 0.46, 95% confidence interval [CI]: 0.81, −0.12). Other domains of physical quality of life (bowel symptoms, urinary incontinence, urinary irritation, and sexual symptoms) did not differ by greenness overall. Psychosocial quality of life did not differ by greenness overall (Q5 vs Q1, odds ratio [95% CI]: memory function: 1.01 [0.61, 1.73]; lack of depressive signs: 1.10 [0.63, 1.95]; and wellbeing: 1.17 [0.71, 1.91]). ConclusionDuring long-term prostate cancer survivorship, cumulative average 1230m greenness since diagnosis was associated with fewer vitality/hormonal symptoms. Other domains of physical quality of life and psychosocial quality of life did not differ by greenness overall. Limitations included potential non-differential exposure measurement error and NDVI's lack of time-activity pattern.

(120) E-Mergir: Preliminary Efficacy of a Digital Psychological Intervention Program for Improving Mental Health, Sexual Health, and Quality of Life of Prostate Cancer Survivors

Abstract Introduction Introduction: Prostate cancer is one of the most common cancers affecting men worldwide. The diagnosis of prostate cancer and associated treatments have a negative impact on people's physical, emotional, and sexual health, compromising their overall well-being and quality of life throughout the course of the disease. Despite the decreased levels of sexual functioning and sexual satisfaction associated with this type of cancer (Quinta-Gomes et al., 2019), patients' access to specialized healthcare and support is still limited. Given their flexibility and convenience, smartphone-based digital interventions can contribute to bridging this gap and constitute an important way to access specialized and personalized supportive care on emotional and sexual health for people with prostate cancer. Objective Objective: The present study aims to evaluate the preliminary efficacy of a digital psychological intervention program using smartphones aimed at improving the mental health, sexual health, and quality of life of prostate cancer survivors. Methods Methods: A randomized controlled pilot study is underway involving 30 prostate cancer survivors randomly assigned to an experimental group (with access to the program) and a waiting list control group (treatment as usual). The program was structured in five modules to be completed by the participants in a maximum period of 6 weeks while receiving support from a psychologist. The study was approved by an institutional Ethical Board. Acceptability, usability, feasibility, and preliminary efficacy (overall improvement in sexual and relational satisfaction, sexual pleasure, sexual distress, psychopathology, and quality of life) were defined as the main outcomes of this study. Participants' assessments will take place in two moments, before and after the implementation of the program. Results Expected results: It is expected that the program and the experimental design adopted will prove to be adequate and have good acceptability by the participants. Improvements in sexual and relational satisfaction, sexual pleasure, sexual distress, psychopathology, and quality of life are also expected for participants using the program compared to those in the waiting-list group. Conclusions Conclusions: As a future empirical-based digital psychological intervention program focused on patients' unmet sexual needs, E-mergir will significantly contribute to addressing the emotional and sexual health and quality of life of people with prostate cancer. Funding: Horizon Europe, NORTE-01-0145-FEDER-000057, CCDRN Disclosure No.

Plant-based diet associated with better quality of life in prostate cancer survivors.

Plant-based diets have many health benefits, including a lower risk of fatal prostate cancer, and greater environmental sustainability. However, less is known regarding the impact of plant-based diets on quality of life among individuals diagnosed with prostate cancer. The authors' objective was to examine the relationship between plant-based diet indices postdiagnosis with quality of life. This prospective cohort study included 3505 participants in the Health Professionals Follow-Up Study (1986-2016) with nonmetastatic prostate cancer. Food-frequency questionnaires were used to calculate overall and healthful plant-based diet indices. Quality-of-life scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations over time between plant-based diet indices and quality-of-life domains (sexual functioning, urinary irritation/obstruction, urinary incontinence, bowel functioning, hormonal/vitality), adjusted for demographics, oncologic history, body mass index, caloric intake, health-related behaviors, and comorbidities. The median age at prostate cancer diagnosis was 68years; 48% of patients underwent radical prostatectomy, and 35% received radiation as primary therapy. The median time from diagnosis/treatment to first the quality-of-life questionnaire was 7.0years. A higher plant-based diet index was associated with better scores for sexual function, urinary irritation/obstruction, urinary incontinence, and hormonal/vitality. Consuming more healthful plant-based foods was also associated with better sexual and bowel function, as well as urinary incontinence andhormonal/vitality scores in the age-adjusted analysis, but not in the multivariable analysis. This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with modestly higher scores in quality-of-life domains among patients with prostate cancer.

Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors

Purpose To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). Materials and methods Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010–2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined ‘persistent’ if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0–100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. Results The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. Conclusions The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Financial hardship and psychosocial well-being and quality of life among prostate cancer survivors in the United States.

Prostate cancer is the most common cancer diagnosis among men in the United States and the prevalence of prostate cancer survivors is growing. Cancer treatment and lasting or late effects of disease and treatment can adversely affect financial health, psychosocial well-being, and health-related quality of life for prostate cancer survivors, even many years after cancer diagnosis and treatment. These outcomes are important, especially because most men live for many years following a prostate cancer diagnosis. In this essay, we describe health care spending associated with prostate cancer, including patient out-of-pocket costs, and summarize research examining medical financial hardship and associations of financial hardship and psychosocial well-being and health-related quality of life among cancer survivors. We then discuss implications for health care delivery and opportunities to mitigate financial hardship for patients with prostate cancer and their families.

Surgery for climacturia following radical prostatectomy: slight modifications necessary in real clinical practice

Adverse events following radical prostatectomy include erectile dysfunction and stress urinary incontinence. However, there are other possible complications potentially affecting quality of life in prostate cancer survivors. Climacturia, or orgasm-associated urinary incontinence, is often overlooked. We used a modified Andrienne's technique to place a compressing graft on urethra in patients who previously underwent radical prostatectomy. One patient (71 years) had moderate erectile dysfunction and total stress urinary incontinence. He was satisfied with wearing a condom catheter, so he declined artificial urinary sphincter placement surgery. Erectile dysfunction and climacturia were bothersome to him, so we performed a three-piece penile implant placement with a «mini-jupette» of porcine dermal collagen, which is a deviation from technique originally described by Andrienne. Another patient (69 years) had severe erectile dysfunction following radical prostatectomy. He was completely continent, so climacturia became evident only after penile implant surgery and «mini-jupette» wasn't placed simultaneously, as originally proposed by Andrienne. We performed treatment for climacturia 1 year later and placed the compressing graft more distally to avoid accidental damage to implant tubing. First patient was successfully treated for erectile dysfunction by implantation of an inflatable device. There was no orgasm-associated urinary incontinence and patient was completely satisfied with his sexual function on follow-up. He continues to use condom catheters, but on some occasions achieves partial inflation of a penile implant, so that «mini-jupette's» tension prevents urinary incontinence. Second patient is also completely satisfied with his sexual function, as climacturia was managed successfully despite distal positioning of «mini-jupette». Penile implant continues to function properly. There are no signs of device failure or infection. Compressing graft can be placed on urethra in patients with three-piece penile implants to prevent climacturia, which is possible after radical prostatectomy. However, slight technical modifications may be required in given cases. Authors have no conflict of interest.

Mapping disadvantage: identifying inequities in functional outcomes for prostate cancer survivors based on geography

BackgroundProstate cancer is the most common internal malignancy in Australian men, and although most patients have good survival outcomes, treatment toxicities can impair function, leading to diminished quality of life for prostate cancer survivors. Socioeconomic disadvantage and geographical remoteness have been shown to be related to worse oncologic outcomes, and it is expected that they would similarly influence functional outcomes in prostate cancer.MethodsUsing data from the Victorian Prostate Cancer Outcomes Registry (n = 10,924), we investigated functional outcomes as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC-26) following prostate cancer treatment, focusing on associations with socioeconomic status and geographical remoteness and controlling for clinicopathologic characteristics. A single composite score was developed from the five separate EPIC-26 domains for use in geo-mapping.ResultsA total of 7690 patients had complete EPIC-26 data, allowing mapping hotspots of poor function using our composite score. These hotspots were observed to relate to areas of socioeconomic disadvantage. Significant heterogeneity in outcomes was seen in urban areas, with hotspots of good and poor function. Both socioeconomic disadvantage and geographical remoteness were found to predict for worse functional outcomes, although only the former is significant on multivariate analysis.ConclusionsGeo-mapping of functional outcomes in prostate cancer has the potential to guide health care service provision and planning. A nuanced policy approach is required so as not to miss disadvantaged patients who live in urban areas. We have demonstrated the potential of geo-mapping to visualise population-level outcomes, potentially allowing targeted interventions to address inequities in quality of care.

Quality of Life of Prostate Cancer Survivors Participating in a Remotely Delivered Web-Based Behavioral Intervention Pilot Randomized Trial.

Background:Following a prostate cancer (PC) diagnosis, treatment-related symptoms may result in diminished quality of life (QoL). Improved diet and increased exercise may improve QoL in men with PC.Methods:We conducted a 4-arm pilot randomized trial to assess feasibility and acceptability of a 3-month web-based diet and exercise intervention, among men (>18 years of age) with PC (reported elsewhere). The purpose of this study is to describe the change in QoL measured by surveys (eg, QLQ-C30, PROMIS Fatigue) at enrollment and following the intervention. Men were randomized 1:1:1:1 to increasing levels of web-based behavioral support: Level 1: website; Level 2: Level 1 plus personalized diet and exercise prescription; Level 3: Levels 1-2 plus Fitbit and text messages; Level 4: Levels 1-3 plus 2 30-minute coaching calls. T-tests were used to compare pre-post change in mean QoL scores between each Level and Level 1.Results:Two hundred and two men consented and were randomized (n = 49, 51, 50, 52 for Levels 1-4, respectively). Men were predominantly white (93%), with a median age of 70 years (Intra-quartile Range [IQR]: 65,75) and 3 years (IQR: 1,9) post primary treatment for mostly localized disease (74% with T1-2). There were no meaningful changes in QoL, but there were notable trends. Level 3 participants had small improvements in QLQ-C30 Global Health (5.46; 95% CI: −0.02, 10.95) compared to Level 1. In contrast, Level 2 participants trended toward decreasing Global QoL (−2.31, 95% CI: −8.05, 3.42), which may reflect declines in function (eg, Cognitive: −6.94, 95% CI: −13.76, −0.13) and higher symptom burden (eg, Diarrhea: 4.63, 95% CI: −1.48, 10.74).Conclusions:This short, web-based intervention did not appear to have an impact on PC survivors’ QoL. Most men were several years past treatment for localized disease; the potential for this approach to reduce symptoms and improve QoL in men who have worse health may still be warranted.

EDITORIAL COMMENT

The authors present a well written analysis on the development of comorbidities in patients awaiting surgery for post-prostatectomy urinary incontinence (PPI). They hypothesize that incontinence my limit physical activity, leading to the development of new health issues. Alterations in both continence and erectile function have a profound influence on the quality of life in prostate cancer survivors.1 Similar studies have shown that incontinence in women leads to decreased physical activity and is a barrier to exercise.

Quality Of Life Of Prostate Cancer Survivors In A Web-based Behavioral Intervention Pilot Trial

Quality Of Life Of Prostate Cancer Survivors In A Web-based Behavioral Intervention Pilot Trial

Effect of the exercise programme on the quality of life of prostate cancer survivors: A randomized controlled trial.

The aim of this study was to investigate the effect of the exercise programme on the quality of life of prostate cancer (PCa) survivors. A randomized controlled, parallel trial was conducted from April 2017 to January 2018 on 80 PCa survivors. They were randomly assigned to intervention and control groups (n = 40 in each group). The exercise programme was designed based on the self-management approach (SMA). The intervention group participated in a 12-week exercise programme consisting of one session of group exercise and three sessions of individual exercise per week using exercise facilities in the community. Data were collected using the quality of life questionnaires and the follow-up checklist. In the intervention group, statistically significant improvements in physical, role, emotional, social and sexual functions were reported. Also, the patients in this group reported reduced fatigue, insomnia, constipation, diarrhoea, urinary, bowel and hormonal treatment-related symptoms in comparison with before the exercise programme (p < 0.05). Nurses are suggested to plan for improving the participation of PCa survivors in exercise programmes using exercise facilities in the community in order to reduce the complications of treatment and improve their quality of life.

The short-term effects of resistance training on quality of life, cancer related fatigue, body composition, and physical function in men with advanced and metastatic prostate cancer receiving androgen deprivation therapy: a pilot study

Background: Prostate cancer, a disease of aging, is the most common cancer for men living in the developed world. Androgen Deprivation Therapy is effective at slowing the progression of prostate cancer cell growth; however, a myriad of musculoskeletal side effects can result from the long-term use. Resistance exercise training has been shown to have a positive effect on quality of life and physical function in cancer survivors.Objective: To measure the short-term effects of an eight-week resistance training program utilizing low cost non-machine based resistive exercise in men with advanced and metastatic prostate cancer.Major Finding: A significant impact on body composition, physical function, and emotional well-being was found after 8 weeks of training.Conclusions: Results suggest that low-cost resistance exercise training conducted in a group setting is effective in improving strength, balance and health-related quality of life in prostate cancer survivors with advanced and metastatic disease.

Psychological distress among prostate cancer survivors in South Korea: A nationwide population-based, longitudinal study.

This time-dependent study aimed to analyze the prevalence of psychological distress in prostate cancer survivors by using claims data in South Korea. In a nationwide cohort, 32005 patients were identified who were diagnosed with prostate cancer between January 2010 and December 2014. We referred the diagnostic codes of mental disorders as psychological distress. We categorized the prevalence of psychological distress based on age and specific times before and after the cancer diagnosis. The median age at diagnosis of prostate cancer was 70 years. Among 32005 patients, 3074 (9.6%) were diagnosed at least once with a mental disorder between 1 year before the cancer diagnosis and the last follow-up. Among the first diagnoses of each patient, the common mental disorders were anxiety (39.1%) and depression (33.0%). In the total cohort, there were 54666 claims for mental disorders and over 48.0% (26256) were for depression. The frequency of psychological distress peaked just before cancer diagnosis. Anxiety was frequent before diagnosis of prostate cancer, whereas depression was frequent after diagnosis. Although stress reaction/adjustment disorders were relatively high in the younger group, depression was relatively high in the elderly group. Psychological distress in prostate cancer survivors showed different patterns of prevalence between before and after cancer diagnosis, as well as between age groups. Timely diagnosis and intervention for mental health could promote quality of life for prostate cancer survivors.

Urological cancers and mental wellbeing: are we helping our patients? A systematic review of current interventions to support patients

Urological cancers and mental wellbeing: are we helping our patients? A systematic review of current interventions to support patients

Physical activity counselling and referrals by general practitioners for prostate cancer survivors in Australia.

Physical activity is an important component of standard care to ensure quality of life for prostate cancer survivors. This paper describes the frequency of physical activity management (physical activity counselling or referrals) by GPs for prostate cancer survivors. A secondary aim is to explore GP characteristics that may influence physical activity recommendations, such as GP or patient age, GP gender and GP geographical location. Analysis was conducted using the longitudinal survey data from the Bettering the Care and Evaluation of Health (BEACH) study. Consultations where prostate cancer was managed, but not classified as a new problem or associated with palliative care, were included. GPs provided physical activity recommendations at 2.0% (n = 58/2882) of prostate cancer survivorship management contacts. The physical activity management provided was physical activity counselling on 39 occasions and a physical activity referral on 19 occasions. All physical activity referrals were made to physiotherapy. After controlling for potential confounding factors, results showed that younger GPs used physical activity management at four-fold the rate of older GPs, and that GPs in major cities used physical activity management at twice the rate of rural GPs. No patient characteristics influenced physical activity management. Australian GPs rarely incorporate physical activity management as part of their management of prostate cancer. Strategies are needed to increase the frequency with which GPs recommend physical activity for prostate cancer survivors.

Expecting the worst? The relationship between retrospective and prospective appraisals of illness on quality of life in prostate cancer survivors.

Despite a generally good prognosis, many prostate cancer survivors have poor quality of life (QOL). A greater understanding of how psychological appraisals influence QOL is merited given their potentially modifiable nature. In this study, we considered how elements of survivors' retrospective and prospective appraisals relate to QOL. A total of 1229 prostate cancer survivors between 2 and 5years post-diagnosis, identified from a population-based National Cancer Registry, were asked questions on their socio-demographics, health, treatment received, and adverse-effects using a cross-sectional design. QOL was assessed using the EORTC QLQ-C30. Retrospective appraisals were assessed by asking survivors to reflect on their experience of treatment-related adverse-effects compared with their prior expectations. A fear of recurrence scale assessed prospective appraisals of future disease course. A multiple regression model explored the impact of psychological appraisals on QOL, after controlling for socio-demographic, treatment, and health-related factors. The model was significant explaining 37% of variance in QOL. The strongest associate with QOL was fear of recurrence (β=-.29; P<.001). Survivors who experienced side effects that were worse than expected had significantly lower QOL (β=-.10; P=.002). Other significant correlates of lower QOL were presence of comorbidities, having undergone a less invasive treatment, and having more advanced disease. Working at diagnosis and having a higher level of education were significantly associated with higher QOL. Results suggest both retrospective and prospective appraisals are independently related to QOL in prostate cancer. Providing survivors with more information about possible adverse effects of treatment, as well as providing appropriate information regarding future disease progression, may improve QOL.

Machine Learning on a Genome-wide Association Study to Predict Late Genitourinary Toxicity After Prostate Radiation Therapy

Late genitourinary (GU) toxicity after radiation therapy limits the quality of life of prostate cancer survivors; however, efforts to explain GU toxicity using patient and dose information have remained unsuccessful. We identified patients with a greater congenital GU toxicity risk by identifying and integrating patterns in genome-wide single nucleotide polymorphisms (SNPs). We applied a preconditioned random forest regression method for predicting risk from the genome-wide data to combine the effects of multiple SNPs and overcome the statistical power limitations of single-SNP analysis. We studied a cohort of 324 prostate cancer patients who were self-assessed for 4 urinary symptoms at 2years after radiation therapy using the International Prostate Symptom Score. The predictive accuracy of the method varied across the symptoms. Only for the weak stream endpoint did it achieve a significant area under the curve of 0.70 (95% confidence interval 0.54-0.86; P=.01) on hold-out validation data that outperformed competing methods. Gene ontology analysis highlighted key biological processes, such as neurogenesis and ion transport, from the genes known to be important for urinary tract functions. We applied machine learning methods and bioinformatics tools to genome-wide data to predict and explain GU toxicity. Our approach enabled the design of a more powerful predictive model and the determination of plausible biomarkers and biological processes associated with GU toxicity.

Predictors of Patient and Partner Satisfaction Following Radical Prostatectomy.

The diagnosis and treatment of prostate cancer adversely affects the physical and emotional well-being of patients and partners and has been associated with sexual dysfunction in patients and their intimate partners. To identify predictors of sexual satisfaction in prostate cancer survivors and their partners based on a review of the current literature. We performed a comprehensive review of the PubMed database from January 2000 to May 2017 focused on the (i) prevalence of patient and partner sexual dysfunction related to radical prostatectomy, (ii)differences in patient and partner perspectives of sexual function and dysfunction, and (iii) predictors of patient and partner sexual satisfaction after radical prostatectomy. Patient- and partner-reported sexual satisfaction. There is a paucity of published data examining sexual satisfaction in prostate cancer survivors and their partners. Patients and partners can have different expectations of sexual outcomes after radical prostatectomy and different attitudes toward the relative importance of recovery of sexual function after surgery. Available data suggest that patients' and partners' mental and physical health and the quality of communication between them are important contributors to their sexual satisfaction. Patient-perceived partner support also is associated with better patient-reported erectile function and greater relationship satisfaction. Mental health, physical health, quality of interpersonal communication, and patient-perceived partner support appear to be the most important predictors of sexual satisfaction for patients and partners in the post-prostatectomy period. There is a definite need for further research on this topic to develop interventions to improve sexual function and quality of life for prostate cancer survivors and their intimate partners. Guercio C, Mehta A. Predictors of Patient and Partner Satisfaction Following Radical Prostatectomy. Sex Med Rev 2018;6:295-301.

The role of the built environment in a randomized controlled trial to increase physical activity among men with prostate cancer: the PROMOTE trial.

The purpose of the study was to examine the association between the built environment and physical activity (PA) in prostate cancer survivors (PCS), as well as whether built environment factors (walkability, count of sports complexes) were effect modifiers of a PA intervention. Our study included 165 PCS residing in Edmonton, Alberta, from the PROMOTE trial. The PROMOTE trial was a randomized controlled trial of a behaviour change intervention to increase PA and quality of life in PCS. In the PROMOTE trial, 423 PCS were randomly assigned to a standard physical activity recommendation, self-administered implementation intention, or telephone-assisted implementation intention group. PA and quality of life outcomes were assessed at baseline, 1, and 3months. To explore the role of the built environment, this study examined walkability and count of sport complexes. Linear regression analyses revealed that the self-administered intervention group had an increase in self-reported PA minutes/week (β=133.4, 95% CI=-18.9 to 285.6); however, none of the built environment variables were found to be significantly associated with PA. The logistic regression showed that the self-administered intervention group had a significantly greater likelihood of meeting the PA guidelines (OR=2.1, 95% CI=0.9 to 4.9), though no built environment variables were associated with PA levels. Our findings suggest that the built environment was not associated with PA and was not an effect modifier in a PA behaviour change intervention for PCS. Further research is needed before clear conclusions can be generated ( ClinicalTrials.gov number NCT01410656).

MP45-09 RADIATION INCREASED APOPTOSIS OF NITRERGIC NEURONS CULTURED FROM THE MAJOR PELVIC GANGLIA

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2017MP45-09 RADIATION INCREASED APOPTOSIS OF NITRERGIC NEURONS CULTURED FROM THE MAJOR PELVIC GANGLIA Elena Pak, Bridget Koontz, and Johanna Hannan Elena PakElena Pak More articles by this author , Bridget KoontzBridget Koontz More articles by this author , and Johanna HannanJohanna Hannan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1427AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A third of men diagnosed with prostate cancer will undergo radiation therapy (RT) which frequently results in erectile dysfunction (ED). Prostatic radiation is presumed to cause damage to the vasculature and the nerves supplying the penis. There are no effective treatment strategies to prevent or recover radiation-induced ED which significantly impacts the quality of life of prostate cancer survivors. This study examined the impact of low and high radiation on neurite growth, branching and survival of sympathetic and nitrergic neurons cultured from the major pelvic ganglia (MPG). METHODS MPGs collected from male Sprague-Dawley rats (n=6) were dissociated and neurons plated on laminin coated glass cover slips. After 24 hours, neurons were irradiated at 2Gy or 8Gy, grown for an additional 48 hours and then compared to time-matched control neurons. Neurons were fixed and stained with immunofluorescence for neuron-specific class III beta-tubulin to measure axon length and branching, neuronal nitric oxide synthase (nNOS, nitrergic), tyrosine hydroxylase (TH; sympathetic) or TUNEL assay for apoptosis. Images were taken of all neurons on each cover slip at a magnification of 100x. RESULTS Neurite length was unchanged with radiation, however, neurite branching significantly decreased with both doses of radiation (CON: 3.0±0.11, 2Gy: 2.6±0.16, 8Gy: 2.5±0.16; p<0.005). There was a 3 to 4-fold increase in the percentage of apoptotic TUNEL positive neurons in both groups following radiation (p<0.0001). There was no change in the relative number of sympathetic TH positive neurons with radiation. In contrast, a marked decrease in nNOS positive neurons increased with the dose of radiation (CON: 45±4.4%, 2Gy: 20±3.1%, 8Gy: 5±0.7%; p<0.0001). CONCLUSIONS These data demonstrate that RT stimulates an increase in neuronal cell death and a substantial decrease in the number of erectile promoting nitrergic neurons. Although there is no change in neurite length, neurite branching which is essential for the establishment of appropriate neuronal connections and regeneration was impaired. Future studies will examine the impact of prostatic RT in an animal model to determine if these neuronal impairments contribute to ED in order to elucidate the pathological mechanisms to lead to new therapeutic radioprotection strategies for prostate cancer survivors. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e614 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Elena Pak More articles by this author Bridget Koontz More articles by this author Johanna Hannan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...