Prostate cancer is the most common cancer diagnosed in men in Ireland, with the exception of non-melanoma skin cancer. Approximately 2,750 new cases were diagnosed in 2007, accounting for 29.7% of all new male cancer cases in Ireland.¹

Developments in screening and the introduction of prostate-specific antigen (PSA) testing have contributed to this increase in prostate cancer incidence. In addition, improvements in detection and treatment have led to greater numbers of prostate cancer survivors. Recent statistics suggest that, in the absence of any other competing causes of death, 88% of men diagnosed with prostate cancer can expect to be alive in five years.¹

The use of hormone therapy in prostate cancer treatment has also risen dramatically over the past 20 years. Androgen deprivation therapy (ADT) is used as a neoadjuvant therapy prior to other treatments such as radical prostatectomy, external beam radiotherapy and brachytherapy in patients with localised prostate cancer.

ADT is also used in advanced stage metastatic disease, as a monotherapy or as adjuvant therapy after a radical treatment. Indeed, medical suppression of testosterone with ADT, or with anti-androgens, is now more common than surgical suppression via orchiectomy. In Ireland, for example, 34% of prostate cancer patients were treated with hormone therapy between 2004 and 2008¹ and the number of prescriptions for ADT increased in the UK from 33,000 in 1987 to 470,000 in 2004.

Side-effects of androgen deprivation therapy

Androgens, in particular testosterone, are required to maintain muscle strength and bone mineralisation. The reduction in testosterone to castrate levels by androgen deprivation therapy leads to a number of adverse physiological and psychological side-effects. These include changes in body composition, such as an increase in fat mass as well as a decrease in muscle mass and strength; a reduction in bone mineral density with increased risk of osteoporosis; gynaecomastia (development of breast tissue); sexual dysfunction and impotence; and a reduction in haemoglobin levels, which can result in increased fatigue. 

Indeed, a recent systematic review and meta-analysis, carried out by our own research group, highlighted the body composition changes associated with ADT.² This study showed that over the course of ADT treatment, body fat mass will increase on average by 7.7% and lean muscle mass will decrease by 2.8%.²

More worryingly, this increase in fat mass tends to accumulate around the abdomen, predisposing these prostate cancer patients to a higher risk of other comorbid conditions, such as diabetes and cardiovascular disease. In fact, the decline in lean muscle mass will only exacerbate this problem further as a reduction in lean muscle mass results in a lower metabolic rate and lower energy requirements. 

Strategies aimed at conserving lean muscle mass and reducing fat mass are therefore essential to minimise the adverse effects associated with ADT in prostate cancer patients. 

As survival rates increase, the number of prostate cancer patients on long-term ADT is also likely to increase and this is worrying as duration of ADT is positively associated with weight gain. 

Diet and exercise interventions

Pekmezi and Demark-Wahnefried recently carried out a review of the literature on the role of diet and exercise interventions in cancer survivors.³ Although research specific to prostate cancer patients is limited, a number of randomised controlled trials (RCTs) have been completed in the USA. These include the RENEW study (Reach out to ENhancE Wellness), which showed a beneficial effect of a home-based multi-behaviour intervention focused on exercise, and including a low saturated fat, plant-based diet, at reducing the functional decline and improving the quality of life of prostate cancer patients. 

In addition, prostate cancer patients who completed a six-month home-based diet and exercise intervention in Project LEAD (Leading the way in Exercise and Diet) had improved physical functioning.^4,5

These studies demonstrated the beneficial effects of diet and exercise in a mixed group of cancer patients (breast and prostate cancer) but they did not specifically investigate the impact of their interventions in prostate cancer patients on ADT, a subgroup of cancer patients who are most likely to benefit from such an intervention. 

There have been a number of exploratory studies that have investigated the impact of exercise alone in reducing some of the modifiable side-effects associated with ADT. It has been shown, for example, that a 10-20 week exercise intervention is beneficial in helping to alleviate the psychological consequences, such as the fatigue, depression and quality of life changes associated with ADT. Patients also saw improvements in strength and physical fitness. 

At 20 weeks, physical activity interventions have been shown to help prevent weight gain and preserve lean muscle mass in this population of cancer survivors. It is likely that a combined intervention that addresses both dietary intake as well as physical activity could minimise the adverse side-effects of ADT even further, however, no study to date has evaluated the effect of combined dietary and physical activity in ADT patients. 

As a result, we conducted a randomised controlled trial to evaluate the efficacy of a six-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition, fatigue and quality of life typically associated with ADT.⁶

Six-month dietary and physical activity trial

Ninety-four prostate cancer patients were recruited to participate in this six-month study (see Figure 1) and 47 were randomised to receive the diet and physical activity intervention, while 47 were assigned to the control group and received standard care. 

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Table 1 describes the inclusion and exclusion criteria for patients participating in the study. Data collection to test the efficacy of the intervention were collected at baseline, at a three-month follow-up and at a six-month follow-up visit. During baseline and follow-up visits, a number of measurements were taken to evaluate the efficacy of the intervention. These included body composition measurements, such as weight, height, body mass index, waist-hip ratio and % fat mass, as well as fatigue severity scores and a questionnaire to evaluate changes in quality of life.⁶

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Patients in the intervention arm received dietary counselling to help them achieve UK dietary guidelines as described in Table 2. The intervention was individually tailored to the food preferences of the patient and was delivered to the patient’s home. Patients were also encouraged to meet guidelines for physical activity: a minimum of 30 minutes of moderate exercise five days per week in the form of brisk walking.

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Results of the study are currently being analysed and will be published in the near future. However, analyses of baseline body composition data have highlighted the need for a dietary and physical activity intervention in this group of patients.

For example, the average BMI in the study was 30kg/m2 compared to a recommended healthy BMI of 20-25kg/m2. The mean waist circumference was 107cm (42 inches), compared to an ideal waist measurement of 96.5cm (38 inches) as advocated by the International Diabetes Federation, and percentage body fat mass was 32.47% compared with a recommended value of ≤⊇28% for men aged 50-72 years of age. 

As cancer survivors are at a higher risk than the general population of developing other comorbid conditions, these baseline data suggest that dietary and physical activity interventions at the time of ADT initiation are essential in this population. 

Patient guidelines

The World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) concluded in 2007 that there is currently insufficient research to provide evidence-based guidelines on the role of diet and physical activity specifically for cancer survivors.⁷ Instead, they concluded that cancer survivors should follow the same guidelines as for cancer prevention and this is supported by the American Cancer Society (ACS) guidelines for cancer survivors. 

Both groups stress the importance of maintaining a healthy body weight, avoiding excessive weight gain throughout life and following healthy eating and physical activity guidelines.⁸

More recently, the American College of Sports Medicine (ACSM) stressed the importance of remaining physically active after a diagnosis of cancer specifically for prostate and breast cancer survivors.⁹ Although the individual treatment modality will be the deciding factor on the functional abilities of patients, the ACSM suggests that post-surgery patients should return to normal activities as soon as possible. 

The guidelines recommended for our intervention were developed from both the ACS guidelines and the UK healthy eating and physical activity guidelines. Results from our six-month diet and physical activity intervention in prostate cancer patients on ADT will be published shortly and will add to the research supporting the benefits of a healthy lifestyle in prostate cancer survivors, particularly those receiving ADT.

Conclusion 

As the population continues to age and as detection, treatment and management of prostate cancer continues to improve, incidence rates will continue to rise and the number of people living with a prostate cancer diagnosis will continue to grow. As a result, more men with prostate cancer treated with ADT will be at risk of weight gain, increased fat mass and decreased muscle, adding to their risk of other comorbid conditions. It would be prudent to offer prostate cancer patients, at the time of initiation of ADT, some simple dietary and physical activity advice to minimise the side-effects of treatment and to reduce their risk of developing other comorbid conditions, such as diabetes, obesity and coronary heart disease, as well as improving their quality of life. 

References

1. National Cancer Registry Ireland. Cancer in Ireland 2011: Annual report of the National Cancer Registry
2. Haseen F, Murray LJ, Cardwell CR et al. The effect of androgen deprivation therapy on body composition in men with prostate cancer: systematic review and meta-analysis. J Cancer Survivorship 2010; 4(2): 128-139
3. Pekmezi DW, Demark-Wahnefried W. Updated evidence in support of diet and exercise interventions in cancer survivors. Acta Oncologica 2011; 50: 167-178
4. Morey MC, Snyder DC, Sloane R et al. Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial. JAMA 2009; 301(18): 1883-1891
5. Demark-Wahnefried W, Clipp EC, Morey MC et al. Lifestyle intervention development study to improve physical function in older adults with cancer: Outcomes from project lead. J Clin Oncol 2006; 24: 3456-3473
6. Haseen F, Murray LJ, O’Neill RF et al. A randomised controlled trial to evaluate the efficacy of a six-month dietary and physical activity intervention for prostate cancer patients receiving androgen deprivation therapy. Trials 2010; 11: 86
7. WCRF/AICR. Food, Nutrition and the prevention of cancer: A global Perspective Expert Report 2007
8. Doyle C, Kushi LH, Byers T et al. Nutrition, Physical Activity and Cancer Survivorship Advisory Committee; American Cancer Society: Nutrition and physical activity during and after cancer treatment. An American Cancer Society Guide for informed choices. CA Cancer J Clin 2006; 56: 323-353
9. Schmitz KH, Courneya, KS, Matthews C et al. American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors. Med Sci Sports Exer 2010; 42: 1409-1426