Obesity is a major epidemic in the Western world and in developing countries. In the United States, one in three adults is considered obese, a rate that has doubled over the past 20 years and is predicted to double again in the next two decades. While it’s widely recognized that there are many causes of obesity, the two most important are poor eating habits and a sedentary lifestyle — both modifiable factors. Obesity contributes to numerous chronic diseases including coronary artery disease, hypertension and diabetes, all of which are, in turn, associated with other (comorbid) medical conditions. Current international trends indicate that prostate cancer incidence is increasing in countries that have adopted Westernized lifestyles and have higher rates of obesity, suggesting that obesity might be a risk factor for prostate cancer.
The exact association between obesity and prostate cancer is complex and studies in this area are still fairly recent. Hormonal alterations in obesity undoubtedly play an important role in prostate cancer tumour biology. As well, new studies have begun to show that obesity impacts unfavourably on the detection, treatment and progression of this disease, and might contribute to poorer outcomes, including the risk of death.
BMI and risk of mortality
Body mass index (BMI), calculated in weight(kg)/ height(m)2, is the international standard used to classify obesity. Overweight is defined as BMI of 25 to 29.9 kg/m2, obesity is BMI of 30 kg/m2 or more, and normal weight is BMI ranging from 18.5 to 24.9 kg/m2. An important study from the American Cancer Society enrolled 900,000 cancer-free adults and followed them for 16 years to assess their risk of death from cancer. Patients with category I and category II obesity (see box, page 11) were, respectively, 20% and 34% more likely to die from prostate cancer than men of normal weight, showing a positive association between BMI and risk of death from this disease. Other studies have reported that a higher BMI is associated with higher-grade prostate tumours, increased rates of biochemical recurrence after radical prostatectomy (determined by rises in prostate-specific antigen or PSA), and risk of metastasis (spread of cancer) up to 70% higher than in non-obese men.
Difficulties with screening
Screening for prostate cancer may be biased against obese men. Physicians report that the difficulty of performing a proper digital rectal exam in obese men may lead to the possibility of missing a cancer. In addition, obese men have larger prostates, making it more difficult to feel a tumour and harder to find the cancer at the time of biopsy. Third, despite their larger prostate size, obese men generally have lower circulating PSA levels due to hormonal influences associated with obesity. Taken together, these factors might lessen the likelihood that obese men will undergo biopsy before their disease has progressed to a later, more aggressive stage with a poorer prognosis.
Treatment complications
Standard treatment options for localized prostate cancer include radical prostatectomy and external beam radiation therapy (EBRT). Surgeons are often reluctant to operate on obese men because of the risks from obesity-related comorbidities. Moreover, radical prostatectomy can present technical challenges in obese patients. Tumour excision is often poorer than in non-obese patients, contributing to the risk of prostate cancer recurrence.
During conventional EBRT, moderately to severely obese men are prone to large positional shifts of the prostate gland. These “prostate shifts” can result in insufficient dosage delivery at the tumour site, destruction of healthy surrounding tissue, and poorer treatment outcomes with higher risks of recurrence.
Obesity, hormones and prostate cancer
Obesity results in marked alterations in circulating levels of numerous hormones, notably, in relation to prostate cancer, testosterone and insulin. For reasons that are unclear, obesity is linked to lower levels of free circulating testosterone. While testosterone is associated with a higher risk of low-grade disease, recent studies indicate that decreased serum testosterone levels may promote higher tumour grades and more aggressive, poorly differentiated prostate cancers at diagnosis. It’s possible that the lower testosterone levels in obese men may predispose them to develop advanced prostate cancer and may contribute to the higher mortality from the disease.
Obesity is also frequently associated with increased circulating insulin and glucose levels, a condition known as insulin resistance. A recent Harvard/McGill University study reported that prostate cancer patients who were overweight, or had elevated C-peptide levels (indicating abnormally high insulin levels) in their blood before diagnosis are at significantly greater risk of dying from the disease. Patients who were both overweight/obese and had elevated C-peptide levels had a four-fold higher risk of mortality than their non-obese counterparts. Because prostate cancer cells have insulin receptors on their surfaces, it’s possible that insulin acts as a growth factor for prostate cancer.
Fat tissue-specific hormones
Hormones that are specific to adipose (fat) cells play a key role in regulating energy intake/expenditure and other metabolic processes, and are emerging as potential contributors to prostate cancer. Levels of two such hormones, leptin and adiponectin, are increased and decreased, respectively, in obesity. In men with prostate cancer, high leptin and low adiponectin levels in the blood were correlated with higher-grade, larger and more advanced tumours. Further research on how these hormones might contribute to prostate cancer is needed.
Technological advances in screening and treatment
Novel prostate cancer markers: Augmentations in PSA levels are often masked in obese patients and changes in serum PSA levels may reflect prostate diseases other than cancer. New blood biomarkers, more accurate for prostate cancer than PSA, are actively being sought using genomic and proteomic profiling. These exciting new technologies examine the differential expression of genes and proteins in normal and cancer tissues, and it’s anticipated that better diagnostic and treatment measures for prostate cancer will soon emerge.
Image-guided radiation therapy (IGRT): Obese prostate cancer patients may have improved outcomes when treated with IGRT. IGRT uses normal external beam radiation, but with guidance from an imaging system (such as CT scans, ultrasound or X-rays)
just before the patient’s daily radiation session. Doctors compare images taken during the planning process with those taken before each treatment and adjust the dose if needed. This step corrects for prostate shifts prior to radiation delivery, thus leading to improved control in obese patients.
Brachytherapy: Radioactive “seeds” implanted directly into the prostate gland, a treatment known as brachytherapy, may be safer and more beneficial than surgery or EBRT in obese prostate cancer patients. An analysis of patients who underwent brachytherapy found that the six-year PSA failure rates (an indication of recurrence) were no higher for overweight and obese men compared to non-obese men.
PC survivors set an example
Increasing rates of obesity in both the Western world and developing countries make it likely that the risk of prostate cancer related to this epidemic will increase. Vital research is ongoing, but many issues still remain unresolved about the biologic link between these two conditions. Among the most crucial of these for men with prostate cancer are questions like: What role do nutrition and lifestyle play? What impact do obesity and/or weight gain at a particular time in a man’s life have on his risk profile? Once diagnosed with prostate cancer, does losing weight improve his chances of survival?
The problem is urgent, and the hope is that this message will motivate men to adhere to better diets and be more physically active. But a 2008 study by a Canadian research team that analyzed data from a community health survey of more than 114,000 adults offers some encouraging observations. The study reported that while about 18% of cancer survivors were obese (62% of these were males), and only about 21% of cancer survivors were physically active (compared to about 25% of Canadians overall), men who’ve had prostate cancer had the highest levels of physical activity and lowest obesity levels — perhaps a contributing factor in their survival?
Christian Band, PhD, is a medical writer and researcher with training in pharmacology and a broad knowledge
of the cellular and molecular mechanisms of disease. He has extensive experience in academia and the biotech/pharmaceutical industry.
