The study is intended to evaluate the efficacy of a 6 month dietary and physical activity intervention for prostate cancer survivors receiving ADT. The outcomes of interest are body composition, fatigue and quality of life.

We will also describe the nutritional status, dietary intake and physical activity level among prostate cancer survivors in Northern Ireland. The effect of the intervention on dietary intake, level of physical activity, quality of life, fatigue, and psychological stress will be assessed by comparing the intervention group with the controls. Moreover the stages of readiness to change lifestyle behaviours in prostate cancer survivors after diagnosis and during ADT will be measured using the transtheoretical model.

We hypothesize that a diet and physical activity intervention will prevent or reduce weight gain, and minimize the increase in body fat mass typically found in patients treated with ADT in the intervention group compared with the controls. We also hypothesize that the intervention patients will experience less fatigue and will have a better quality of life score compared with the controls.

The dietary advice is developed based on the patients' usual dietary intake, measured at baseline using a 7-day food diary. They are provided with individually tailored advice to encourage them to adopt a diet that is commensurate with current dietary guidelines [¹⁹] and, specifically, to meet the following criteria;

a) Eat 5 or more servings of vegetables and fruits per day

b) Reduce total fat intake to 30%-35% of total energy, with < 10% of energy from saturated fat

c) Limit polyunsaturated fat intake to 10% of daily total energy intake

d) Limit consumption of processed meats

e) Eat fibre-rich foods. Aim to consume 25 to 35 g of fibre daily

f) Limit alcohol intake ≤ 28 units/week

g) Limit intake of foods high in salt and/or sugar

Brisk walking at least 30 min per day, in addition to usual activities on 5 or more days of the week.

The diet and physical activity intervention is tailored to each patient based on the information collected during their baseline interview. The nutritionist meets each patient to discuss their calculated energy and nutrient requirements. Dietary recommendations are based on the information collected on weight, physical activity levels and baseline dietary intake. Energy is calculated based on actual body weight; however, 500 kcal/day reduction is advised to the overweight/obese patients to prevent or reduce weight gain. Each patient in the intervention arm receives an individualised guidebook with tips and guidelines to help adherence to the diet. The guidebook includes; a sample menu to provide an example of the amounts and type of foods that can be included for breakfast, lunch, dinner and snacks; a list of portion sizes for foods typically eaten; tips to incorporate more fruit, vegetables and fibre, and reduce total fat, saturated fat, sugar and salt; a list of healthier foods choices and a list of foods that should be chosen less frequently from all food groups; examples of healthy alternative menus for breakfast, snacks, lunch and dinner.

The physical activity intervention is also tailored to each patient based on their baseline physical activity level. As a minimum, each patient is asked to walk at a brisk pace for at least 30 minutes per day, 5 times or more per week. However, men who are already physically active are advised to increase the duration and frequency of walking each week. They are also asked to set a goal of increasing the number of steps by at least 10% every week. A pedometer is provided to each participant in an effort to encourage them to comply with the physical activity intervention and as an independent measure of physical activity levels during the intervention period.

Men in the control group will receive standard care during the intervention period but will be offered the same guidelines at the end of the 6 month intervention.

Measures of body composition include percentage body fat (assessed from skin fold thickness measured at 4 sites; triceps, biceps, subscapular and suprailiac using a Harpenden Skinfold Calipers), height, (measured to the nearest centimetre using SECA Leicester Height Measure), weight (SECA 704 Electronic Column Scale), body mass index (BMI) (Kg/M²), waist and hip circumference as a measure of central adiposity and mid upper arm circumference as a measure of lean body mass. A standard protocol is used to conduct all anthropometric measurements [²⁰].

The Fatigue Severity Scale (FSS) is a self-reported scale and has been used previously in prostate cancer patients treated with ADT [²¹] and in patients with advanced stage cancer of the prostate [²²]. Patients are asked to report their degree of agreement (on a seven-point scale) with nine items related to fatigue. Therefore, scores can range between 9 (indicating minimum fatigue) and 63 (indicating maximum fatigue). The validity of this scale is supported by its good correlation with both the EORTC Fatigue scale (Spearman Rank Correlation Coefficient r = 0.83) and the bi-dimensional fatigue scale (r = 0.62). A previous study of cancer related fatigue reported that 95% of an elderly control population without cancer scored less than 42 on the FSS scale [²²]. Therefore, in this study 'severe fatigue' for cancer patients was defined as a score of 42 or greater based on the results of a study by Stone et al in prostate cancer patients treated with ADT [²¹].

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) is used to assess prostate cancer related quality of life [²³]. The FACT-P is a 40-item self-reported questionnaire assessing a range of quality of life domains: physical, social/family, emotional, and functional well being. In addition, a 12-item prostate cancer subscale (PSC) which is specific to the symptoms and side effects associated with prostate cancer treatment such as body image, pain, urinary and sexual functioning is also used. Responses to questions use a five-point Likert-type scale ranging from 0 (not at all) to 4 (very much). The scores are summed to produce a subscale score for each domain assessed. The subscale scores range from 0 to 28 for the physical, social/family, and functional well being scales, 0 to 24 for the emotional well being scale, and 0 to 48 for the PSC, and higher scores represent better quality of life. The scores of these four domains are summed to calculate the FACT-G (Functional Assessment of Cancer Therapy-General) and total scores of FACT-G and PSC are added up to produce a FACT-P score. An additional score, the Trial Outcome Index (TOI) is created by summing the physical well-being, functional well-being and PCS scores. This instrument has been used previously in prostate cancer patients receiving ADT [²⁴]. It has been considered a reliable instrument with sensitivity to change in prostate specific antigen (PSA) scores and performance status [²³].

To reduce the possibility of memory recall problems for this older patient group a 7-day food diary (7DD) is used to assess food and nutrient intake. The patients are asked to record, in as much detail as possible, all food and beverages consumed over a 7-day period. The food diary contains instructions for completion, one page to record foods and drinks eaten during seven time points (before breakfast, breakfast, before lunch, lunch, before dinner, dinner, after dinner) and alcohol over a 7 day period. The instructions included the provision of typical portion sizes to help the patients to indicate the amount of each food consumed. Patients are also encouraged to describe the portion size consumed using other measures if they wish, such as weight in grams or ounces, or in household units, such as tablespoons, cups, slices etc. At the time of the patients' visit the trained nutritionist clarified any omissions and collected additional information if required such as the cooking methods used, brands of foods consumed and portion sizes if these were unclear. The 7DD has been used in the UK EPIC (European Prospective Investigation of Cancer and Nutrition) study [²⁵] amongst others and is a manageable method for our population. It has been demonstrated that a 7DD provides a better estimate of average intake than a food frequency questionnaire or a 24 hour-recall [²⁵,²⁶]. A computer based software programme (WISP) will be used to interpret the food intake data to provide nutrient and food group intake estimates. The total number of servings of fruit and vegetable consumed will be calculated using the Food Standard Agency guidelines [¹⁹].

A fasting blood sample is collected for analysis of serum ferritin, antioxidant vitamins, dietary lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), C-reactive protein and albumin. A total of 30 ml of blood is collected and following appropriate processing for serum and plasma are stored in -80°C freezer.

Physical activity is assessed with 7-Day Physical Activity Recall (7-DPARQ) [²⁷,²⁸]. This is an interviewer-administered measure assessing current and recent past physical activity from the last 7 days. Information on moderate, hard and very hard activities and time spent sleeping is gathered from the interview and light activities is imputed from the time remaining. Additionally, patients report how typical the week's activity is compared to their activity in the previous three months. The 7-DPARQ measures energy expenditure and yields a summery score in kcal/kg^-1/day^-1 for the previous week. It has been validated and used for prostate cancer patients in previous studies [¹²,²⁹].

Functional capacity is measured using a 6-min Walk Test [³⁰,³¹], which was used in previous studies of prostate cancer patients [⁹,²⁹]. This test includes a measure of the distance walked, to the nearest metre in 6 minutes. This functional measure was chosen rather than a measure of physiological fitness as it appears to be a more suitable outcome for an elderly population [²⁹]. The 6-min walk test has a high test-retest reliability over a 2-week time frame (r = 0.87) [³²].

Psychological stress is assessed using the Perceived Stress Scale (PSS-10), which is the most widely used psychological instrument for measuring the perception of stress among prostate cancer survivors [^33-35]. The PSS-10 is a 10-item questionnaire designed to measure the perceived stress and the degree to which patients found their lives unpredictable, uncontrollable, or overloaded in last 1 month. Questions are rated on a 4-point Likert scale with responses ranging from 0 = "never" to 4 = "very often." [³⁶]

The transtheoretical model (TTM) is used to assess a patients' readiness to change their lifestyle behaviour [³⁷]. Patients will be categorised according to their stage of readiness to change and this information will be taken into consideration in the analysis and interpretation of the impact of the intervention. Patients are asked, 'on average do you - eat at least 5 servings of vegetables and fruits each day; avoid eating too much fat; walk 30 minutes every day at a brisk pace, 3 to 5 times/week?'. Responses include: Yes - 'more than six months' (interpreted as maintenance), 'less than six months' (interpreted as action); No - 'intend to in the next 30 days' (interpreted as preparation), 'intend to in the next 6 months' (interpreted as contemplation) and not intending to in the next 6 months (interpreted as pre-contemplation). Stage of readiness to change is also considered in the delivery of the intervention. For example, the potential benefit of a dietary and physical activity intervention is really emphasised to those men who are in a stage of contemplation/precontemplation with respect to making diet and physical activity changes.

A structured questionnaire is used to collect information on age, socioeconomic status, education, family and social support, tobacco and alcohol intake, barriers to exercise and diet, supplementation use and family history of prostate cancer. A clinical history, including the date of diagnosis, stage of disease and treatment details is recorded from the patient's medical notes during screening. Data related to adverse events are collected continuously via follow-up phone call.