IGF-1 and hyperglycaemia-induced FOXA1 and IGFBP-2 affect epithelial to mesenchymal transition in prostate epithelial cells.

Localized prostate cancer (PCa) is a manageable disease but for most men with metastatic disease, it is often fatal. A western diet has been linked with PCa progression and hyperglycaemia has been associated with the risk of lethal and fatal prostate cancer. Using PCa cell lines, we examined the impact of IGF-I and glucose on markers of epithelial-to-mesenchymal transition (EMT), migration and invasion. We examined the underlying mechanisms using cell lines and tumour tissue samples. IGF-I had differential effects on the process of EMT: inhibiting in normal and promoting in cancer cells, whereas hyperglycamia alone had a stimulatory effect in both. These effects were independent of IGF and in both cases, hyperglycaemia induced an increase IGFBP-2(tumour promoter) and FOXA1. A positive correlation existed between levels of IGFBP-2 and FOXA1 in benign and cancerous prostate tissue samples and in vitro and in vivo data indicated that FOXA1 strongly interacted with the IGFBP-2 gene in normal prostate epithelial cells that was associated with a negative regulation of IGFBP-2, whereas in cancer cells the level of FOXA1 associating with the IGFBP-2 gene was minimal, suggesting loss of this negative regulation. IGF-I and hyperglycaemia-induced FOXA1/IGFBP-2 play important roles in EMT.

Prostate cancer survivors' preferences on the delivery of diet and lifestyle advice: a pilot best-worst discrete choice experiment.

BACKGROUND: Lifestyle factors, including diet and physical activity, are associated with prostate cancer progression and mortality. However, it is unclear how men would like lifestyle information to be delivered following primary treatment. This study aimed to identify men's preferences for receiving lifestyle information. METHODS: We conducted a cross-sectional pilot best-worst discrete choice experiment which was nested within a feasibility randomised controlled trial. Our aim was to explore men's preferences of receiving diet and physical activity advice following surgery for localised prostate cancer. Thirty-eight men with a mean age of 65 years completed best-worst scenarios based on four attributes: (1) how information is provided; (2) where information is provided; (3) who provides information; and (4) the indirect cost of receiving information. Data was analysed using conditional logistic regression. Men's willingness to pay (WTP) for aspects of the service was calculated using an out-of-pocket cost attribute. RESULTS: The combined best-worst analysis suggested that men preferred information through one-to-one discussion ß = 1.07, CI = 0.88 to 1.26) and not by email (ß = - 1.02, CI = - 1.23 to - 0.80). They preferred information provided by specialist nurses followed by dietitians (ß = 0.76, CI = 0.63 to 0.90 and - 0.16, CI = - 0.27 to - 0.05 respectively) then general nurses (ß = - 0.60, CI = - 0.73 to - 0.48). Three groups were identified based on their preferences. The largest group preferred information through individual face-to-face or group discussions (ß = 1.35, CI = 1.05 to 1.63 and 0.70, CI = 0.38 to 1.03 respectively). The second group wanted information via one-to-one discussions or telephone calls (ß = 1.89, CI = 1.41 to 2.37 and 1.03, CI = 0.58 to 1.48 respectively), and did not want information at community centres (ß = - 0.50, CI = - 0.88 to - 0.13). The final group preferred individual face-to-face discussions (ß = 0.45, CI = 0.03 to 0.88) but had a lower WTP value (£17). CONCLUSIONS: Men mostly valued personalised methods of receiving diet and physical activity information over impersonal methods. The out-of-pocket value of receiving lifestyle information was important to some men. These findings could help inform future interventions using tailored dietary and physical activity advice given to men by clinicians following treatment for prostate cancer, such as mode of delivery, context, and person delivering the intervention. Future studies should consider using discrete choice experiments to examine information delivery to cancer survivor populations.

Phase II randomised control feasibility trial of a nutrition and physical activity intervention after radical prostatectomy for prostate cancer.

OBJECTIVE: Dietary factors and physical activity may alter prostate cancer progression. We explored the feasibility of lifestyle interventions following radical prostatectomy for localised prostate cancer. DESIGN: Patients were recruited into a presurgical observational cohort; following radical prostatectomy, they were offered randomisation into a 2×3 factorial randomised controlled trial (RCT). SETTING: A single National Health Service trust in the South West of England, UK. PARTICIPANTS: Those with localised prostate cancer and listed for radical prostatectomy were invited to participate. RANDOMISATION: Random allocation was performed by the Bristol Randomised Trial Collaboration via an online system. INTERVENTIONS: Men were randomised into both a modified nutrition group (either increased vegetable and fruit, and reduced dairy milk; or lycopene supplementation; or control) and a physical activity group (brisk walking or control) for 6 months. BLINDING: Only the trial statistician was blind to allocations. PRIMARY OUTCOME MEASURES: Primary outcomes were measures of feasibility: randomisation rates and intervention adherence at 6 months. Collected at trial baseline, three and six months, with daily adherence reported throughout. Our intended adherence rate was 75% or above, the threshold for acceptable adherence was 90%. RESULTS: 108 men entered the presurgical cohort, and 81 were randomised into the postsurgical RCT (randomisation rate: 93.1%) and 75 completed the trial. Of 25 men in the nutrition intervention, 10 (40.0%; 95% CI 23.4% to 59.3%) adhered to the fruit and vegetable recommendations and 18 (72.0%; 95% CI 52.4% to 85.7%) to reduced dairy intake. Adherence to lycopene (n=28), was 78.6% (95% CI 60.5% to 89.8%), while 21/39 adhered to the walking intervention (53.8%; 95% CI 38.6% to 68.4%). Most men were followed up at 6 months (75/81; 92.6%). Three 'possibly related' adverse events were indigestion, abdominal bloating and knee pain. CONCLUSIONS: Interventions were deemed feasible, with high randomisation rates and generally good adherence. A definitive RCT is proposed. TRIAL REGISTRATION NUMBER: ISRCTN 99048944.

TReatIng Urinary symptoms in Men in Primary Healthcare using non-pharmacological and non-surgical interventions (TRIUMPH) compared with usual care: study protocol for a cluster randomised controlled trial.

BACKGROUND: Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. In men, the prevalence and severity of LUTS increases with age, with a significant impact on quality of life. The majority of men presenting with LUTS are managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as the initial treatment. However, the provision of conservative therapies in primary care is variable and can be time and resource limited. GPs require practical resources to enhance patient engagement with such interventions. TRIUMPH aims to determine whether a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for LUTS versus usual care. METHODS/DESIGN: TRIUMPH is a two-arm, cluster randomised controlled trial (RCT) being conducted in 30 National Health Service (NHS) general practices in England. The TRIUMPH intervention comprises a standardised LUTS advice booklet developed for the trial with patient and healthcare professional (HCP) consultation. The booklet is delivered to patients by nurses/healthcare assistants following assessment of their urinary symptoms. Patients are directed to relevant sections of the booklet, providing the manualised element of the intervention. To encourage adherence, HCPs provide follow-up contacts over 12 weeks. Practices are randomised 1:1 to either deliver the TRIUMPH intervention or a usual care pathway. The patient-reported International Prostate Symptom Score (IPSS) at 12 months post consent is the primary outcome. Secondary outcomes include cost-effectiveness, patient-reported outcomes on LUTS, quality of life, and patient and HCP acceptability and experience of the intervention. Primary analyses will be conducted on an intention-to-treat basis. DISCUSSION: It is unclear whether conservative therapies for male LUTS are effectively delivered in primary care using current approaches. This can lead to men being inappropriately referred to secondary care or experiencing persistent symptoms. Primary care, therefore, holds the key to effective treatment for these men. The TRIUMPH intervention, through its standardised and manualised approach, has been developed to support GP practices in delivering effective conservative care. This pragmatic, cluster RCT should provide robust evidence in a primary-care setting to inform future guidelines. TRIAL REGISTRATION: ISCRTN registry, ID: ISRCTN11669964 . Registered on 12 April 2018.

Body image issues and attitudes towards exercise amongst men undergoing androgen deprivation therapy (ADT) following diagnosis of prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is an established treatment for prostate cancer (PCa), but its side-effects can affect body appearance and functioning. However, research into the impact of ADT on body image is limited. Exercise can help patients to counterbalance some side-effects, potentially improving body image too. However, adherence to exercise recommendations is low. Therefore, we explored body image after ADT and attitudes towards exercise. METHODS: Twenty two semi-structured interviews were conducted with PCa patients receiving ADT (Mage = 67.9 years old, SD = 9.99). RESULTS: Participants expressed appearance dissatisfaction focusing on body feminization. Participants exercised to counterbalance ADT side-effects and improve mood. Exercise also helped them to re-establish a sense of control over their body and experience a sense of achievement. However, some men described being worried that their appearance and physical performance would be judged by others, so they often exercised alone or gave up exercise. Time management and fatigue were also identified as exercise barriers. CONCLUSION: These findings highlight the need to further investigate body image concerns and exercise barriers in PCa patients undergoing ADT. These results could also inform support groups and health care professionals on the topic. However, further research should explore the most effective and acceptable ways to provide support to PCa patients on body image issues.

Health behaviours of young mothers: Implications for health promotion and cancer prevention.

OBJECTIVE: Evidence suggests that younger mothers engage in poorer health behaviours, resulting in increased cancer risk. We aimed to better understand the health behaviours of younger mothers and the factors that influence their lifestyle choices, in order to improve cancer prevention within this population. METHODS: A multiple focus group, photo-elicitation-aided approach was used, in which young mothers (n = 27; aged 16-24 years) were provided with cameras and asked to capture 'a week in your life'. Photographs were developed and participants invited to an initial focus group where photographs were used to elicit discussion, exploring participants' health behaviours. Data were thematically analysed particularly identifying themes relating to barriers and facilitators of positive health behaviours. Participants were later invited to participate in a second focus group, to explore and validate identified themes further. RESULTS: Themes emerged from the data relating to (1) the mothers' personal perceptions of health, (2) health-related behaviours and (3) beliefs about cancer and its causes. Barriers to positive health behaviours included a lack of money, childcare and cookery skills; facilitators included the social media, commercial weight loss programmes and local community organisations. CONCLUSION: Study findings provide insight into the health behaviours and life choices of young mothers. They help illustrate health perceptions in relation to cancer risk, providing an understanding of how their daily routine and circumstance influence young women's decisions and lifestyle behaviour choices and highlighting barriers to, and facilitators of, positive health behaviours. Data hold potential to inform future health-related research among young mothers, particularly relating to cancer prevention intervention.

Acceptability of dietary and physical activity lifestyle modification for men following radiotherapy or radical prostatectomy for localised prostate cancer: a qualitative investigation.

BACKGROUND: The experience and acceptability of lifestyle interventions for men with localised prostate cancer are not well understood, yet lifestyle interventions are increasingly promoted for cancer survivors. We explored the opinions, experiences and perceived acceptability of taking part in nutritional and physical activity interventions amongst men with prostate cancer and their partners; with the ultimate plan to use such information to inform the development of nutritional and physical activity interventions for men with prostate cancer. METHODS: Semi-structured interviews with 16 men, and seven partners, undergoing curative surgery or radiotherapy for prostate cancer. Interviews explored experiences of lifestyle interventions, acceptable changes participants would make and perceived barriers and facilitators to change. Interviews were thematically analysed using the framework approach. RESULTS: Men were frequently open to lifestyle modification and family support was considered vital to facilitate change. Health beneficial, clinician endorsed, understandable, enjoyable interventions were perceived as attractive. Barriers included 'modern' digital technology, poor weather, competing commitments or physical limitations, most notably incontinence following radical prostatectomy. Men were keen to participate in research, with few negative aspects identified. CONCLUSIONS: Men are willing to change behaviour but this needs to be supported by clinicians and health professionals facilitating lifestyle change. An 'intention-behaviour gap', when an intended behaviour does not materialise, may exist. Digital technology for data collection and lifestyle measurement may not be suitable for all, and post-surgery urinary incontinence is a barrier to physical activity. These novel findings should be incorporated into lifestyle intervention development, and implemented clinically.

The feasibility of the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) dietary and physical activity modifications: a qualitative study.

BACKGROUND: There is increasing evidence that low levels of physical activity and diets low in fruit and vegetables and high in meat and dairy products are risk factors for prostate cancer disease progression. The Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) aimed to assess a diet and physical activity intervention in men undergoing radical prostatectomy for localized prostate cancer. The trial included a qualitative component to explore the experiences of men participating in the trial in order to understand the acceptability of the intervention and data collection methods. We report the qualitative findings of the trial and consider how these can be used to inform future research. METHODS: PrEvENT involved randomizing men to either a dietary and/or physical activity intervention. Semi-structured interviews were conducted with a purposive sample of 17 men on completion of the 6 month trial. Interviews took place in clinic or as telephone interviews, if requested by the participant, and were audio recorded, transcribed, and analyzed using the thematic-based framework approach. Analysis was conducted throughout the data collection process to allow emergent themes to be further explored in subsequent interviews. RESULTS: Three overarching themes were identified: acceptability of the intervention, acceptability of the data collection methods and trial logistics. Participants were predominantly positive about both the dietary and physical activity interventions and most men found the methods of data collection appropriate. Recommendations for future trials include consideration of alternative physical activity options, such as cycling or gym sessions, increased information on portion sizes, the potential importance of including wives or partners in the dietary change process and the possibility of using the pedometer or other wearable technology as part of the physical activity intervention. CONCLUSIONS: We provide insight into the opinions and experiences of the acceptability of the PrEvENT diet and physical activity intervention from the participants themselves. The interventions delivered were acceptable to this sample of participants, as were the data collection methods utilized. We also highlight some considerations for further behavioural change interventions in prostate cancer and other similar populations. TRIAL REGISTRATION: ISRCTN, ISRCTN99048944 . Registered on 17 November 2014.

The provision of dietary and physical activity advice for men diagnosed with prostate cancer: a qualitative study of the experiences and views of health care professionals, patients and partners.

PURPOSE: To explore the views and experiences of health care professionals (HCPs), men diagnosed with localised prostate cancer and their partners about the provision of advice on diet and physical activity after diagnosis and treatment for localised prostate cancer. METHODS: Semi-structured in-depth interviews with ten HCPs (Consultant Urological Surgeons, Uro-Oncology Clinical Nurse Specialists and Allied Health Professionals: see Table 1) and sixteen men diagnosed with localised prostate cancer and seven of their partners. Data from interviews were thematically analysed using the Framework Approach. RESULTS: The men and their partners provided differing accounts to the HCPs and sometimes to each other concerning the provision of advice on diet and physical activity. Some men were unable to recall receiving such advice from HCPs. Factors impacting upon advice-giving included the perceived lack of an evidence base to support dietary and physical activity advice and the credibility of advice providers. The timing of advice provision was a contentious issue as some HCPs believed that patients might not be willing to receive dietary and physical activity advice at the time of diagnosis, whilst others viewed this an opportune time to provide behaviour change information. Patients concurred with the latter opinion. CONCLUSIONS: Men and their partners would value nutritional and physical activity advice from their HCP, after a localised prostate cancer diagnosis. Men would prefer to receive this advice at an early stage in their cancer journey and may implement behaviour change if the received advice is clear and evidence-based. HCPs should receive suitable training regarding what information to provide to men and how best to deliver this information.

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

BACKGROUND: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. METHODS/DESIGN: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). DISCUSSION: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality.

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions.

Physical activity, alcohol consumption, BMI and smoking status before and after prostate cancer diagnosis in the ProtecT trial: opportunities for lifestyle modification.

Associations between certain lifestyle characteristics and prostate cancer risk have been reported, and continuation post-diagnosis can adversely affect prognosis. We explored whether men make spontaneous changes to their physical activity and alcohol intake, body mass index (BMI) and smoking status, following a diagnosis of localised prostate cancer. A detailed diet, health and lifestyle questionnaire was completed by 511 participants within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial, both before and 9 months after a diagnosis of prostate cancer. Of 177 men who were insufficiently active before their diagnosis (median 0 activity units/week; IQR 0-9), 40.7% had increased their activity by a median of 22 U week(-1) (IQR 15-35) 9 months later, and there was weak evidence that men were more active after diagnosis than before (p = 0.07). Men categorised as "working" occupational social class and who were insufficiently active before diagnosis were 2.03 (95%, CI = 1.03-3.99, p = 0.04) times more likely to have increased their physical activity levels compared to men classified as "managerial or professional." Similarly, men who were insufficiently active pre-diagnosis and with T-stage 2 compared with T-stage 1 prostate cancer were 2.47 (95%, CI = 1.29-4.71, p = 0.006) times more likely to be sufficiently active post-diagnosis. Following diagnosis, there was an overall reduction in alcohol intake (p = 0.03) and the proportion of current smokers (p = 0.09), but no overall change in BMI. We conclude that some men spontaneously change certain lifestyle behaviours on receiving a diagnosis of prostate cancer. For many men, however, additional support through lifestyle interventions is probably required to facilitate and maintain these changes.