Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol

Prostate cancer has become the most significant major malignancy of men, severely impacting disease-specific morbidity and mortality [1–3]. Advances in treatment of the disease, particularly through the use of Androgen Deprivation Therapy (ADT; a primary and mainstay treatment of prostate cancer), has seen prostate cancer 5-year survival rate increase to 92% [2]. Despite ADT’s efficacy in disease control, the physiological alterations resulting from ADT have profound adverse effects, including increased fatigue [4, 5], metabolic risk [6–8], cardiovascular risk [6, 9], change in body composition (increased fat mass and decreased muscle mass) [10, 11], and reduced functional capacity [12]; the amalgamation of these side effects severely reduces quality of life [13–15]. Cancer-related fatigue (CRF) is a distressing, persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning [16]. CRF is the most common adverse effect of ADT, with up to 74% of men treated with ADT experiencing symptoms of CRF [4]. Incidence of CRF can be seen as early as 12 weeks after treatment initiation, and may last for longer than 12 months post-treatment in men treated with ADT [4, 5, 17]. Given the widespread use of ADT in managing prostate cancer progression, many men are living with ADT-related side effects during the course of treatment, and longer into prostate cancer survivorship. Current management strategies of CRF are predominantly through pharmacological therapy [16, 18]; yet more recently, natural therapies such as diet and exercise have demonstrated clinically significant reductions of CRF symptoms in men with prostate cancer treated with ADT [19, 20].

The benefits of aerobic exercise (performed at 65–80% age predicted maximum heart rate [APMHR] three times per week) and progressive resistance training (8–12 exercises, 2–4 sets of 8–12 repetitions performed 2–3 times per week) in isolation, or when prescribed together, are well established for improving CRF in men with prostate cancer [21–25]. Recently, there has been particular interest in the use of high intensity interval training [85–95% peak heart rate (HR_peak) interspersed with period of active recovery] for improving CRF, body composition, and quality of life in oncological populations for managing treatment-related side effects [26–28]. In colorectal cancer survivors, 12 supervised high intensity interval training sessions (4×4 min bouts of cycling at 85–95% HR_peak, interspersed with 3 min of active recovery at 50–70% HR_peak) performed over 4 weeks showed greater improvements in cardiorespiratory fitness and total body mass, when compared to 12 supervised moderate intensity exercise sessions (50 min of cycling at 50-70% HR_peak) [29]. Thus, high intensity interval training may provide an optimal exercise prescription for improving various aspects of health that are typically impaired with ADT; however exercise at this intensity is yet to be conducted in men with prostate cancer.

Combined nutrition therapy and exercise prescription has the potential to optimize management for CRF and other ADT related side effects. Aerobic exercise (55–80% APMHR) performed 2-3 times per week for 12-weeks, with healthy eating group based seminars every 2 weeks, has demonstrated clinically significant improvements in CRF and quality of life in sedentary men treated with ADT [19, 20]. In contrast individual nutrition advice to meet the United Kingdom Dietary guidelines [30] with 30 min per day of brisk walking for 24 weeks demonstrated no significant changes in CRF or quality of life compared to usual care [31]. Thus it appears CRF may be better managed with structured exercise prescription and concurrent healthy eating. Whilst Bourke and colleagues [19, 20] demonstrated significant improvements in CRF, the nutrition consults were group-based, which fails to consider individual dietary requirements and is not representative of standard dietetic practice. Thus the effects of tailored nutrition therapy beyond the healthy eating guidelines, with adjunctive structured exercise prescription on the burden of CRF remains to be elucidated.

Dietary manipulation has been identified to be an important lifestyle factor to alleviate ADT related side effects [32–34]; yet the efficacy of dietary interventions in isolation during treatment or into prostate cancer survivorship are limited for supporting the adverse side effects seen from ADT. Importantly, prostate cancer-specific dietary guidelines provide limited support and guidance for alleviating adverse treatment-related side effects, including CRF [35, 36]. In non-oncological populations, structured individualized nutrition therapy by an Accredited Practising Dietitian is recommended for adults who are overweight, obese, insulin resistant, and have altered lipid and triglyceride metabolism [37–39]; all notable adverse side effects from ADT. Yet the translation of this nutrition therapy in prostate cancer is yet to be elucidated. Recently, a Mediterranean-style diet pattern has been shown to improve metabolic and cardiovascular parameters in men at risk of prostate cancer [40]. Adherence to an anti-inflammatory properties of a Mediterranean diet have shown small reductions in hypertension (reduced systolic blood pressure; SE?=?– 1.44mm Hg [95% CI, -2.88 – 0.01]; and diastolic blood pressure; SE?=?-0.70mm Hg [95% CI, -1.34 – 0.07) [41], and risk of type 2 diabetes (RR?=?0.93; 95% CI, 0.89 – 0.98) [42]; thus showing plausible metabolic and cardiovascular effects on known ADT related side effects. Yet practical application of the Mediterranean-style diet pattern to men treated with ADT for management of CRF and improving quality of life is yet to be ellucidated.

Literature to date has encompassed general healthy eating guidelines for the management of prostate cancer treated related side effects [19, 20, 31], however general guidelines do not take into account the specific dietary requirements needed to manage the ADT-related side effects. Therefore, the role of specific individualized nutrition therapy tailored to alleviate the side effects of ADT, particularly CRF, and improve quality of life warrants investigation.

This study aims to:

1. 1.

   Investigate whether 12-weeks of nutrition therapy, compared to 12 weeks of usual care, can improve prostate CRF and quality of life in men treated with ADT.

2. 2.

   Assess the combined benefits of 20-weeks of nutrition therapy with 8-weeks of high intensity exercise (weeks 12–20), compared to 20 weeks of usual care, on CRF and quality of life in men treated with ADT.

We hypothesized that 12-weeks of nutrition therapy, compared to 12 weeks of usual care, will improve CRF and quality of life in men with prostate cancer treated with ADT. It is further hypothesized a 20-week nutrition therapy intervention with 8 weeks of high intensity interval training, compared to 20 weeks of usual care, will improve CRF and quality of life in men with prostate cancer treated with ADT. Secondary measures of body composition, functional capacity, metabolic syndrome and biomarkers such as prostate specific antigen, insulin like growth factor [43]-1, IGF-2, IGF binding protein-3, interleukin [IL]-6, and IL-8), will be measured and analyzed between and within groups. We hypothesis nutrition therapy alone, and with high intensity exercise will improve body composition, functional capacity, and biomarkers of metabolic syndrome and prostate cancer progression.