Endometrial cancer is the most common gynecologic cancer in the United States and obesity is the most significant risk factor. A recent prospective study reported that nearly 70% of women with early endometrial cancer were obese.1 In general, most patients with early-stage disease do well; however, those who are obese are at significant risk for comorbidity. Single-institutional studies suggest that endometrial cancer survivors suffer from obesity-related comorbidities including diabetes, hypertension, and cardiovascular disease.2–4 In addition, obese endometrial cancer patients have a higher mortality from causes not related to cancer.5 Therefore, it is imperative to study this patient population after treatment to design intervention strategies to improve their morbidity and mortality.
The American Cancer Society in 2006 recommended that survivors maintain a healthy lifestyle that includes a normal weight, not smoking, being physically active, and maintaining a healthy diet to improve prognosis and well-being.6 Unfortunately, the majority of cancer survivors do not engage in a healthy lifestyle.7 Research has shown that in endometrial cancer survivors, exercise and body weight are independent factors in quality of life (QOL).8 Quality of life is correlated with overall survival in some survivor groups.9 Therefore, if a patient's QOL is purposely improved, it may be possible to increase overall survival.
We previously reported on the feasibility of a 6-month lifestyle intervention in overweight endometrial cancer survivors.4 The intervention resulted in behavior change and weight loss over a 1-year period. We are presently completing a multi-institutional prospective lifestyle study to measure outcomes in a larger population with an enhanced intervention. This current ancillary study was conducted to examine lifestyle behaviors in survivors that may contribute to their morbidity and QOL. We hypothesized that the majority of endometrial cancer survivors would not be meeting healthy lifestyle guidelines and that the failure to meet these guidelines would be associated with poorer QOL.
MATERIALS AND METHODS
Baseline data from two prospective, randomized, lifestyle intervention trials conducted in early-stage endometrial cancer survivors were merged. The studies were funded by the Lance Armstrong Foundation (2005–2007) and the American Cancer Society (2008–current). The studies were conducted at University Hospitals Case Medical Center and the Cleveland Clinic in Cleveland, Ohio, and approved by the University Hospitals and Case Cancer Institutional Review Boards. Results of the first completed study (Lance Armstrong Foundation) are reported elsewhere4 and the American Cancer Society trial is currently ongoing. Eligibility criteria for both studies included 1) stage I–II (early stage), endometroid (type I) endometrial cancer diagnosis with primary surgical staging procedure with or without adjuvant radiation therapy, 2) recurrence-free at the time of recruitment, 3) body mass index (BMI) of 25 or greater, 4) performance status of 0–2, and 5) diagnosis within the previous 5 years.
Demographic data were collected by a research assistant and from medical record chart review. Patients completed questionnaires on comorbidities, smoking status, physical activity, and fruit and vegetable intake. Lifestyle behaviors were compared with American Cancer Society guidelines for cancer survivors (150 min/wk of moderate to strenuous physical activity, five servings fruit or vegetables per day, no smoking).6
Patient demographic and clinical data were obtained at baseline enrollment in either the Lance Armstrong Foundation or the American Cancer Society study. All patients recruited to the trial were considered “early survivors” and were within 5 years of their diagnosis. Physical activity was measured with the Leisure Score Index of the validated Godin Leisure-Time Exercise questionnaire.10 The participant was asked to complete a four-item query of leisure-time habits. Average frequency of mild (minimal effort, no perspiration), moderate (not exhausting, light perspiration), and strenuous (heart beats rapidly, sweating) physical activity during a typical week was assessed along with average duration in number of minutes. Minutes of physical activity was assessed by multiplying the frequency by the duration and combining the minutes of moderate and strenuous activity together. Reliability and validity of the Leisure Score Index is comparable with other self-report measures,11 and the questionnaire has been used in previous trials of physical activity in cancer survivors.12 Fruit/vegetable intake was assessed using the National Cancer Institute (NCI) All-Day Fruit and Vegetable Screener.13 This was completed only for the American Cancer Society trial.
The Short Form Medical Outcomes (SF-36) survey was used to measure functional health and well-being.14 It consists of 36 questions scored on a Likert scale, producing overall physical and mental component summary measures. The SF-36 has proven useful in monitoring general and specific populations, comparing the burden of different diseases, and differentiating the health benefits produced by different treatments. Reliability estimates range from 0.89 to 0.94 for physical and 0.84 to 0.91 for mental summary measures, and scores vary with age, sex, presence of disease, or other conditions.14 The Functional Assessment of Cancer Therapy–General (FACT-G) version 4 is a 27-item questionnaire evaluating physical, functional, family-social, and emotional well-being QOL domains. Subscale scores range from 0 to 28 for all domains except for emotional well-being (0–24), and total FACT-G score range is from 0 to 108.15 A fatigue subscale is validated (range 0–52).16
Participants were weighed in street clothes without shoes and weight was recorded to the nearest 0.1 kg. Height was measured on a stadiometer and recorded to the nearest 0.1 cm. BMI was computed (weight in kilograms divided by square of their height in meters) and categorized according to National Heart, Lung and Blood Institute guidelines: 25.0 to 29.9 was considered overweight, 30 to 39.9 obese, and morbid obesity was 40.0 kg/m2 or higher.17 Anthropometric measures of waist/hip circumference were also done. A patient was considered as having metabolic syndrome, if three of the following five criteria were met: waist circumference more than 35 inches, current medication use for elevated triglycerides, reduced HDL-C level, hypertension, or elevated glucose level.18
Demographic, clinical, and baseline variables were summarized overall. The percentage of participants meeting each lifestyle behavior recommendation was calculated and a 95% confidence interval (CI) was computed. Behaviors were examined by BMI status (BMI less than 40 compared with 40 or higher) and time since diagnosis (less than 1 year, 1–2 years, and more than 2 years since diagnosis) by χ2 test. To examine the associations between lifestyle behaviors and QOL, median scores for the SF-36 physical and mental composite summary score and FACT-G total score and domains (well-being scores and fatigue module) were compared by nonparametric Mann-Whitney test. Effect sizes (d) were calculated for the difference in means as d=(Mean1−Mean2)/SDpooled. Effect sizes of d=0.2 are considered small, d=0.5 moderate, and d=0.8 large.19 Lifestyle clusters were formed using the following categories: those who met no lifestyle behavior, met the smoking-only behavior, met the physical activity plus smoking behavior, met the five-a-day plus nonsmoking recommendations, or met all three lifestyle behaviors as in previous research.7,20 Clusters were compared by nonparametric Kruskal-Wallis test and effect sizes for the difference in means between clusters were computed. Mean scores were adjusted for age, BMI, education, and marital status. SPSS 14.0 was used for analysis.
One hundred-twenty patients were enrolled in both studies, 45 patients in the Lance Armstrong Foundation study and 75 patients in the American Cancer Society study. Recruitment procedures and feasibility of the Lance Armstrong Foundation study have been previously reported.4 Similar recruitment methods are being used for the American Cancer Society study. Participant characteristics for the two studies were similar and are presented in Table 1. Mean age of participants overall was 56.8 (SD=9.5) years and 36% received adjuvant radiation treatment after surgery. Forty-three percent of participants had hypertension, 35% osteoarthritis, 33% metabolic syndrome, and 21% type 2 diabetes mellitus. Ninety percent of participants were at very or extremely high risk for development of type 2 diabetes, hypertension, and cardiovascular disease according to national guidelines.17 Participants used a mean of 2.5 medications and had an average Beck depression score of 9.8 (SD=7.9) at baseline.
Mean participant BMI was 38.6 (SD=9.0) kg/m2 (Table 2). More than 40% of participants had a BMI higher than 40 (corresponding to morbid obesity) at baseline. Ninety-three percent of participants had abdominal obesity (waist circumference more than 35 inches) with a mean waist circumference of 41.8 (SD=5.3) inches; 75% had waist-to-hip ratio more than 0.80. Excess fat in the abdomen is an independent predictor of risk for chronic disease such as hypertension, cardiovascular disease, and diabetes mellitus.21
At baseline, 80% of women reported no strenuous exercise and 54% no moderate exercise; only 12% were meeting the physical activity guidelines of at least 150 minutes of moderate to strenuous physical activity per week (Table 3). Forty-one (34%) participants reported 60 minutes or more of moderate to strenuous exercise per week and only 58 (48%) reported any moderate to strenuous physical activity at all. Median number of minutes of any physical activity (including mild activity) was 70 minutes (interquartile range=167). Fifteen percent reported consuming five or more servings of fruit or vegetables or both per day, mean intake was 2.6 servings per day with 0.9 servings of fruit per day and 1.5 servings of vegetables per day. Seventy-four percent of patients were nonsmokers. There were differences noted between patients meeting lifestyle behavior guidelines by BMI status. For smoking, 60/73 (82%) of patients with BMI lower than 40 were nonsmokers compared with 29/47 (62%) of patients with a BMI higher than 40 (P=.018). For physical activity, 11/73 (15%) of patients with BMI lower than 40 were meeting the guideline compared with 3/47 (6%) of patients with a BMI higher than 40 (P=.243). No differences were noted based on time since diagnosis.
When dividing survivors into lifestyle clusters (Table 3), eighteen participants (15%) met the physical activity plus smoking recommendation or the five-a-day fruit or vegetable servings plus smoking recommendation, 68 (57%) met the nonsmoking behavior recommendation only, 26 (22%) met no behaviors, and only 1% met all three American Cancer Society lifestyle guidelines. Seven (6%) participants who were smokers but met either the physical activity or five-a-day fruit or vegetable servings goal were excluded from the lifestyle cluster analysis as this group (n=7) was too small to be included.
Quality of life scores for participants meeting compared with not meeting each of the three lifestyle behaviors are presented in Table 4. Results reveal small to moderate differences in QOL among individual lifestyle behaviors. With regard to physical activity, notable effect sizes were observed in the FACT domains of physical (d=0.35), mental (d=0.31), and functional well-being (d=0.30) and fatigue (d=0.36) and SF36 PCS (d=0.57). There was no relationship between five-a-day fruit or vegetable servings and QOL nor with social well-being and any of the lifestyle behaviors (data not shown). The effect of following nonsmoking guidelines on QOL was limited to physical well-being (d=0.20), emotional well-being (d=0.53), and fatigue (d=0.47).
We found small to moderate differences in QOL scores when combining lifestyle behaviors into clusters (Table 5). There was no association between meeting physical activity guidelines with nonsmoking or five-a-day fruit or vegetable servings with nonsmoking. There were small to moderate effects for the clustering for meeting nonsmoking recommendation only and meeting no behaviors. The largest effect sizes were for meeting no behaviors and emotional well-being (d=0.66) and fatigue (0.62).
The obesity epidemic in the United States has changed the patient demographics for obstetrician, gynecologists. Treating the obese patient is problematic in obstetrics–gynecology and in cancer. There are more than 1 million gynecologic cancer survivors in the United States and endometrial cancer survivors are the most common.22 These patients have multiple comorbidities resulting in higher mortality from causes not related to cancer. In this series hypertension, metabolic syndrome, diabetes, and central adiposity were common. In addition, 90% of participants were at high risk for development of cardiovascular disease. Participating in one positive lifestyle behavior may serve as a stimulus for another healthy lifestyle.20 Unfortunately, only 1% of participants met all three American Cancer Society lifestyle guidelines, less than what is described in the literature for other cancer survivor groups.7 Visceral obesity, measured by waist circumference or waist-to-hip ratio, has been recognized as an important pathogenic factor for cardiovascular disease.23 Many metrics of measurement, including BMI, anthropometrics, and medical history support that these patients are at risk for premature death.1,3,5
The majority of endometrial cancer survivors do not have an active lifestyle, and research has shown that survivors who engage in healthier lifestyles have better outcomes.24–27 The Nurses' Health Study revealed that those who walked more than 3 hours a week had improved overall survival.27 Other studies have concluded that physical activity improved patient outcomes.25,26 An analysis of lifestyle and survival in the Women's Healthy Eating and Living trial found that improving nutrition quality (five or more daily servings of vegetables-fruits) along with walking 30 minutes 6 days per week was associated with a significant survival advantage.28,29 The breast cancer literature indicates better outcomes for women who improve the quality of their diet after diagnosis. In the Women's Intervention Nutrition Study, there was a lower incidence of recurrence in those on a lowfat diet.30 Another study of breast cancer patients indicated that women following a high-quality diet had a significant decreased risk of overall death and death from non–breast cancer causes.31 Fifteen percent of endometrial cancer survivors in this study are eating five servings of fruits and vegetables a day, less than other survivorship groups.
Blanchard et al analyzed six different types of cancer patients enrolled in the American Cancer Society's Study of Cancer Survivors.7 Their endometrial cancer group included long-term survivors, advanced disease, and patients receiving chemotherapy. We chose to focus our studies on the most common endometrial cancer group, those with type I (obesity driven). In addition, we focused on survivors within 5 years to engage the “teachable moment” for health change.32 In their endometrial cancer patients, 30% met physical activity, 20% five-a-day fruit or vegetable servings, and 91% nonsmoking, compared with our 12%, 15%, and 74%, respectively.7 In addition, it is quite concerning that 26% of the patients, the majority of whom are obese, are smokers, as this further increases their risk for cardiovascular disease.
Physical activity has been correlated with QOL in endometrial cancer survivors.7,8 Global QOL scores did not differ with physical activity in this study. This could be related to sample size or it could be that the largest effect is in the physical domain of QOL and not seen in the mental domains. Research is less clear with regard to smoking and nutrition, and there has been no research in specific domain QOL effects. Meaningful differences in QOL have been defined as 2–3 points for FACT-G subscales and 3–4 points for fatigue.33 In this study, differences in QOL between those meeting lifestyle guidelines were small, but did approach 2–3 points for functional well-being, emotional well-being, and fatigue for physical activity and smoking behaviors. The negative effect between smoking and physical well-being and fatigue is not surprising. However, the effect between smoking and emotional well-being is intriguing and should be targeted in future interventions.
There are several limitations to the study including those inherent to ancillary analyses. Patients recruited were all overweight and therefore, there is not a comparative normal weight control group. Although it may not be surprising that overweight endometrial cancer patients have an unhealthy lifestyle, it is necessary to study the lifestyle variables to design appropriate interventions. Lifestyle modification may have occurred in patients who were further out from their diagnosis or there may not have been adequate time for change to occur in patients enrolled closer to diagnosis; however, this is unknown. Racial minorities were underrepresented despite focused recruitment strategies. Our study is also limited by small sample size, and the exclusion of extreme elderly. Subgroups were small as there was a limited number of patients meeting the American Cancer Society guidelines. Recall and response bias may have been a factor as patients were asked to recall number of fruit or vegetable servings knowing that their health care providers recommend five servings. Other potential unknown confounders include education, race, and marital status.
Every cancer survivorship group has unique and unmet needs with inherent patient characteristics, biology of disease, and treatment effects. Endometrial cancer survivors are unique in that they are usually obese and have multiple medical comorbidities. Most have early-stage and grade disease and are told they are “cured.” However, clinicians should educate their patients on the significant risk for morbidity and mortality related to their lifestyle behaviors.
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