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The roles of diet, physical activity, and body weight in cancer survivors

The roles of diet, physical activity, and body weight in cancer survivors
Authors:
Jennifer Ligibel, MD
Jeffrey A Meyerhardt, MD, MPH
Section Editor:
Patricia A Ganz, MD
Deputy Editor:
Sonali Shah, MD
Literature review current through: Jun 2022. | This topic last updated: May 31, 2022.

INTRODUCTION — With advances in early detection and treatments for cancer, there are approximately 32.6 million people alive globally with a history of cancer (within five years of diagnosis), as of 2012 [1]. Novel methods to improve outcomes, especially those that are also associated with improvements in quality of life and other health benefits, may offer attractive additions to the currently available treatment options.

Obesity and other factors related to energy balance have been linked to outcomes in several cancers, including breast cancer, endometrial cancer, prostate cancer, and colorectal cancer. We will provide an overview of the many studies that have looked at the feasibility and potential benefits of energy balance interventions in survivors of these cancers. In addition, we provide consensus-based recommendations for cancer survivors.

Weight, diet, and physical activity, as they relate to survivors of other cancers, including lung cancer, ovarian cancer, and head and neck cancers, are discussed separately:

(See "Overview of approach to lung cancer survivors", section on 'Addressing risk behaviors'.)

(See "Approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma", section on 'Promoting a healthy lifestyle'.)

(See "Overview of approach to long-term survivors of head and neck cancer", section on 'Diet and exercise'.)

An overview of cancer survivorship is also discussed separately. (See "Overview of cancer survivorship care for primary care and oncology providers".)

Topics addressing diet, physical activity, and weight in patients without a history of cancer are discussed separately:

(See "Healthy diet in adults" and "Obesity in adults: Dietary therapy".)

(See "Physical activity and exercise in older adults" and "The benefits and risks of aerobic exercise" and "Obesity in adults: Role of physical activity and exercise".)

(See "Overweight and obesity in adults: Health consequences" and "Obesity: Genetic contribution and pathophysiology" and "Obesity in adults: Prevalence, screening, and evaluation" and "Obesity in adults: Overview of management".)

(See "Overview of cancer prevention".)

(See "Factors that modify breast cancer risk in women", section on 'Alcohol use and smoking'.)

ENERGY BALANCE IN CANCER — Diet, physical activity, and weight are collectively considered energy balance factors because they describe the relationship between energy consumed (diet), energy expended (physical activity), and energy stored (adiposity). Obesity, inactivity, poor dietary quality, and the metabolic syndrome are linked to decreased overall and cancer-specific survival in individuals with cancer [2-6]. A positive energy balance results from excess of energy intake relative to the energy expended, which results in increases in the storage of energy and weight gain [7].

The definition of metabolic syndrome is discussed elsewhere. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Definition'.)

Studies have demonstrated that interventions targeting weight, diet, and physical activity are feasible, can improve quality of life (QOL), and may minimize disease and treatment-related side effects for cancer survivors [3,8,9]. Some preliminary evidence suggests that lifestyle change may also improve prognosis in individuals with early stage cancers [10], but much work still needs to be done to validate this and to determine which types of lifestyle change are most important.

Diet — Prospective studies of diet and chronic diseases have facilitated major advances in our understanding of the contribution of diet to the pathogenesis of disease [11]. They suggest that changes in dietary patterns might help reduce the risk of many common diseases in the United States, including some cancers. The potential impact of dietary patterns upon prognosis in patients with cancer has also been widely studied and is discussed in the sections below, according to disease type. (See 'Breast cancer' below and 'Prostate cancer' below and 'Colorectal cancer' below.)

In a meta-analysis of 117 cohort studies enrolling 209,597 cancer survivors, adherence to a high-quality diet and a prudent, healthy dietary pattern was inversely associated with overall mortality among cancer survivors, whereas a Western dietary pattern was positively associated with overall mortality in this population [12].

The role of specific dietary regimens as a complementary or alternative treatment for cancer is discussed separately. (See "Complementary and alternative therapies for cancer".)

Weight — Obesity is a well-established risk factor for many cancers including multiple myeloma, breast, gastrointestinal (eg, colorectal, gastric, liver, pancreatic, gallbladder), kidney, uterine, and ovarian cancers [13-19]. A number of studies have also linked obesity to an increased risk of cancer recurrence and mortality [7,20,21].

The morbidity and mortality associated with being overweight or obese have been known to the medical profession for more than 2000 years [22]. "Overweight" refers to a weight above the "normal" range, which is determined by calculating the body mass index (BMI, defined as the weight in kilograms divided by height in meters squared). Overweight is defined as a BMI of 25 to 29.9 kg/m2, and obesity as a BMI of >30 kg/m2. (See "Definition, epidemiology, and etiology of obesity in children and adolescents" and "Obesity in adults: Prevalence, screening, and evaluation".)

Given the increasing evidence linking obesity and cancer, the American Society of Clinical Oncology made Obesity and Cancer one of its core initiatives in 2013 to 2014 [23]. The Initiative focuses on building awareness of the links between obesity and cancer within the oncology community, building a robust research agenda in this area, and advocating for access to weight management programs for oncology patients.

Physical activity — Exercise is associated with improved survival and patient reported outcomes in most cancer survivors, and it is safe to perform in both the adjuvant and posttreatment settings.

Exercise and prognosis — Observational studies have reported a link between exercise and improved survival in cancer survivors, with most of the data coming from survivors with breast, colorectal, or prostate cancers [2,5,24-31].

Growing evidence also suggests that sedentary behavior, time spent engaged in activities such as TV-watching and computer use, may be an independent risk factor for poor prognosis in cancer survivors as well as for cancer risk in the general population [32,33]. For example, a meta-analysis of 14 studies including individuals with and without cancer demonstrated that sedentary behavior was associated with an increased risk of all-cause mortality (22 percent), cardiovascular mortality (15 percent), cancer mortality (14 percent), and incidence of type 2 diabetes (91 percent) [32]. Some cancer survivors may benefit from physical activity [34] and exercise rehabilitation to prevent or mitigate such risks. (See "Physical rehabilitation for cancer survivors", section on 'Cardiotoxicity'.)

Data for the association between increased physical activity and lower cancer risk in the general population are discussed separately. (See "Overview of cancer prevention", section on 'Physical activity'.)

Exercise and outcomes in cancer survivors — The American College of Sports Medicine (ACSM) has reviewed data from multiple randomized trials and concluded that exercise could safely be performed in both the adjuvant and posttreatment settings [24,29].

Additionally, the ACSM evaluated data on the impact of exercise interventions on patient-reported outcomes in cancer survivors [29]. They concluded that there was strong evidence that exercise (optimally combined aerobic exercise and resistance training) led to reductions in anxiety, depressive symptoms, and cancer-related fatigue, and improvements in health-related QOL and physical function [24,25,29,35-39]. While the exercise regimens from trials for each outcome differ slightly, general recommendations would be at least 30 minutes of aerobic exercise three times per week and resistance training twice a week. Additionally, supervised resistance training led to reductions in lymphedema symptoms in breast cancer survivors. Notably, the majority of the data were derived from studies in breast cancer survivors. (See "Cancer-related fatigue: Treatment", section on 'Exercise'.)

EVIDENCE RELATED TO SPECIFIC CANCERS

Breast cancer

Diet — Some evidence suggests that reducing dietary fat intake after a cancer diagnosis could improve breast cancer outcomes in cancer survivors, but the data have not been consistent, and dietary modification is not a standard part of adjuvant therapy for women with breast cancer at this time.

Studies have focused both upon intake of specific dietary nutrients as well as on broader dietary patterns (eg, ingestion of a fruit and vegetable-based diet versus a diet high in processed foods, red meat, and fat) [40]. However, any relationships between breast cancer outcomes and any dietary pattern or intake of a particular nutrient have been inconsistent, especially after adjustment for body weight and other related factors. Examples of meta-analyses and large-scale reviews are summarized below:

A 2016 meta-analysis of 41 observational studies found an association between ingestion of a prudent dietary pattern (a diet rich fruits, vegetables, and whole grains and low in red and processed meats) and decreased risk of overall mortality (relative risk [RR] 0.76, 95% CI 0.71-0.89) [12]. Conversely, the analysis showed ingestion of a Western-pattern diet (a diet rich in red meat, processed foods, and sugary snacks) was associated with a significantly higher risk of overall mortality (RR 1.44, 95% CI 1.17-1.77). Alcohol use after breast cancer diagnosis was also associated with an increased risk of breast cancer recurrence (RR 1.21, 95% CI 1.06-1.39) but not overall mortality (RR 0.94, 95% CI 0.85-1.04).

The World Cancer Research Fund (WCRF) reviewed the evidence and concluded that lower fat intake, particularly saturated fat, and higher intake of food containing fiber and soy are associated with lower breast cancer mortality. However, the group concluded that it was not possible to determine whether these effects were causative. WCRF therefore did not generate specific dietary recommendations for breast cancer survivors, instead suggesting that breast cancer survivors follow the WCRF dietary recommendations for cancer prevention [41].

Two large-scale randomized trials have examined the impact of dietary modification on disease outcomes in early stage breast cancer but with differing results:

The Women's Interventional Nutrition Study (WINS) randomized 2437 women with stages I to IIIa breast cancer to a low-fat dietary intervention or usual care control group [10]. After a median follow-up of 5.6 years, dietary intervention improved disease-free survival (DFS; hazard ratio [HR] 0.76, 95% CI 0.60-0.98), although with longer follow-up, the difference was no longer significant [10]. A survival analysis presented after 383 deaths demonstrated no benefit of the dietary intervention in the study population overall, but exploratory subgroup analysis suggested that patients with hormone receptor-negative cancers continued to experience benefits from the intervention (HR for mortality 0.46, 95% CI 0.27-0.78).

In the Women's Healthy Eating and Living (WHEL) study, women with stages I to IIIa breast cancer were randomly assigned to low-fat, high-fruit and vegetable diet or to a control group [42]. Those assigned to the dietary intervention increased intake of fruits and vegetables and decreased percentage of dietary calories from fat, but there was no difference in the rate of recurrence between the groups at a median follow-up for 5.6 years (16.7 versus 16.9 percent).

The reason for the differences in outcomes of these studies is not clear. Many experts have attributed the improvements in DFS seen in the WINS trial to the weight loss experienced by participants; this hypothesis is currently being tested in a number of randomized trials. Given the discrepancies in findings of WINS and WHEL, dietary change has not been widely adopted as a part of the adjuvant treatment of breast cancer patients. For a discussion of the effect of weight loss interventions on outcomes in breast cancer survivors, please refer to the separate section within this topic. (See 'Effects of weight loss on cancer outcomes' below.)

Low-fat dietary patterns in postmenopausal women (who may be at risk for breast cancer) and healthy diet in the general population (not specifically in cancer survivors) are discussed separately. (See "Healthy diet in adults" and "Factors that modify breast cancer risk in women", section on 'Low-fat dietary pattern in postmenopausal women'.)

Weight — Obesity at diagnosis appears to be a risk factor for worse outcomes after a diagnosis of breast cancer. However, the impact of weight gain following diagnosis and the influence of interventions aimed at weight loss on outcomes require further study.

Weight at diagnosis — Obesity at the time of breast cancer diagnosis has been linked to worsened outcomes, both in clinical trials as well as in observational studies.

As examples of these data:

A meta-analysis presented by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) including 80,000 women in 70 different adjuvant trials demonstrated a 5 percent absolute increase in mortality in obese versus normal-weight premenopausal women with hormone receptor-positive disease [43].

In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial, women who had a body mass index (BMI) ≥35 kg/m2 had a 60 percent higher risk of recurrence as compared with women with a BMI <25 kg/m2 [44]. A similar result was noted among obese premenopausal women treated with ovarian suppression and anastrozole in the Austrian Breast Cancer Study Group 12 (ABCSG-12) study [45]. (See "Adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Obese women'.)

Obese women with hormone receptor-positive tumors treated with chemotherapy (doxorubicin, cyclophosphamide, and a taxane) in the Eastern Cooperative Oncology Group E1199 trial had a 20 percent higher risk of recurrence as compared with leaner women [46]. (See "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer", section on 'Obese women'.)

Observational studies also consistently link obesity at the time of breast cancer diagnosis to higher rates of breast cancer recurrence, cancer-related mortality, and overall mortality [20,47,48]. Several meta-analyses of observational studies demonstrated that women who were obese at diagnosis had a higher risk of breast cancer mortality and overall mortality compared with leaner women [47,48]. This increased risk of mortality was seen in both pre- and postmenopausal women [47] and across various breast cancer subtypes [48].

The etiology of the poor outcomes seen in obese women with breast cancer is not well understood. Some older observational studies did not take treatment factors into consideration, introducing potential bias into these reports. Historically, many oncologists used ideal body weight or capped the absolute doses of chemotherapy administered to obese patients due to fears of increased toxicity. Studies subsequently demonstrated that these practices resulted in inferior outcomes [49,50], leading the American Society of Clinical Oncology to develop guidelines recommending the use of full, weight-based doses of chemotherapy for obese individuals. This topic is discussed separately. (See "Dosing of anticancer agents in adults", section on 'Overweight/obese patients'.)

Weight after diagnosis — Weight gain after a breast cancer diagnosis may be associated with an increased risk of recurrence, although the available data do not consistently report this association [51]. As examples:

In the Nurses' Health Study (NHS), nonsmoking women previously treated for breast cancer who gained 0.5 to 2 kg/m2 and women who gained more than 2 kg/m2 had an increased risk of breast cancer death compared with women who maintained a stable weight (RR 1.35, 95% CI 0.93-1.95 and RR 1.64, 95% CI 1.07-2.51, respectively) [52].

In a combined analysis of 3215 women from the Life After Cancer Epidemiology (LACE) cohort and the WHEL study control group, weight gain after diagnosis was not associated with an increased risk of recurrence, even in individuals who gained >10 percent of body weight [53].

Effects of weight loss on cancer outcomes — Despite the abundant data linking obesity and poor prognosis in early breast cancer, there have been relatively few studies evaluating the efficacy and potential benefits of weight loss interventions in breast cancer survivors [54,55]. Several trials have demonstrated that weight loss programs can be successfully implemented in breast cancer survivors and that weight loss can be achieved through a number of different approaches [9,56-61]. However, more research is needed to determine whether purposeful weight loss after breast cancer diagnosis leads to improvements in the risks of breast cancer recurrence and related mortality.

Several large-scale trials have evaluated the feasibility and benefits of weight loss in women with breast cancer. Data are as follows:

The Lifestyle Intervention Study for Adjuvant Treatment of Early Breast Cancer (LISA) randomly assigned 338 postmenopausal women with hormone receptor-positive breast cancer to a two-year telephone-based weight loss intervention or to usual care [9]. LISA demonstrated that women randomized to the intervention lost more weight than controls at one and two years post-randomization as compared with controls (loss of 5.4 percent of baseline weight versus 0.7 percent at one year; and loss of 3.7 percent of baseline weight versus 0.4 percent at two years). Patients in the intervention group also reported significant improvements in physical functioning scores as compared with control participants [9]. Long-term follow-up demonstrated that women who had been randomized to the weight loss group had a nonsignificant reduction in breast cancer recurrence, but the study lacked power to evaluate this endpoint.

The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial randomized 692 women with a history of breast cancer to a group-based weight loss program or to a less intensive control group that received two meetings with a dietitian and nontargeted print materials [61]. Individuals randomized to the group-based intervention group lost more weight at one and two years post-randomization compared with controls (loss of 6.0 versus 1.5 percent at one year and 3.7 versus 1.3 percent at two years). Intervention participants also had lower blood pressure at one and two years post-randomization compared with controls.

Preliminary findings from the German SUCCESS C trial did not demonstrate benefit from a telephone-based weight loss program on disease outcomes in a subset of overweight and obese women with breast cancer taking part in an adjuvant chemotherapy trial [62]; however, interpretation of these findings is complicated by a high dropout rate (approximately 52 percent of intervention participants dropped out during the two-year intervention period, versus 19 percent of controls) and modest weight loss in the intervention arm. In this study, 2292 patients were randomized to either telephone-based, lifestyle-interventional (LI) counseling or general recommendations for healthy lifestyle. In the intention-to-treat analyses, there were no differences in DFS (HR 0.91, 95% CI 0.70-1.18) or overall survival (HR 0.90, 95% CI 0.63-1.28) between the study arms.

More work is needed to determine if weight loss of the magnitude seen in LISA and ENERGY will result in improvements in breast cancer-specific and overall mortality [61]. A number of ongoing large-scale efforts will provide more information about the impact of lifestyle intervention upon breast cancer outcomes in the coming years:

The Italian DIANA-5 trial tests the impact of a Mediterranean diet in combination with increased physical activity on breast cancer outcomes and serum biomarkers in women with early breast cancer [63].

The Breast cancer WEight Loss (BWEL) trial will test the impact of a telephone-based weight loss intervention on invasive DFS in 3136 overweight and obese women with stage II to III breast cancer in the United States and Canada [64].

Physical activity — Although there is no clear consensus on the "best" type of physical activity for breast cancer survivors, benefits have been seen with a number of types of exercise, and the safety of moderate-intensity exercise has been shown [65]. Data from observational studies show that women who participate in a moderate amount of physical activity after diagnosis have improved outcomes as compared with less active women [2,5,66-68]. However, randomized trials of interventions aimed at increasing physical activity have not been large enough to evaluate whether such interventions improve breast cancer outcomes among survivors.

A meta-analysis of 16 prospective observational studies in breast cancer survivors demonstrated a 48 percent reduction in overall mortality (95% CI 0.42-0.64) and a 28 percent reduction in breast cancer mortality (95% CI 0.60-0.85) in the most versus least active breast cancer survivors. There was a 24 percent (95% CI 11-36 percent) reduction in overall mortality for each 10 metabolic equivalent task-hour/week increase in postdiagnosis physical activity (equivalent to current recommendations of 150 minutes/week of at least moderate intensity activity). Breast cancer survivors who increased their activity after diagnosis relative to prediagnosis levels also had a lower risk of overall mortality (RR 0.61, 95% CI 0.42-0.80) compared with survivors who decreased levels of activity or were inactive at both time points [69].

Numerous randomized trials have tested the feasibility and potential benefits of increasing exercise after diagnosis in breast cancer patients [24,29,70-75]. Although data are limited for the impact of physical activity upon breast cancer outcomes, they suggest that exercise improves multiple clinical outcomes in breast cancer survivors including mental health (anxiety, depression), cancer-related fatigue, physical function and aerobic fitness, strength, health-related quality of life (QOL), body image, body size, and body composition. General exercise recommendations from the American College of Sports Medicine (ACSM) for cancer survivors, including breast cancer, are discussed above. (See 'Exercise and outcomes in cancer survivors' above.)

The impact of upper body strength training on symptoms, such as lymphedema, is discussed separately. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Diet and exercise'.)

Prostate cancer

Diet — There appears to be an association between dietary fat intake and outcomes for men with prostate cancer. However, the impact of dietary interventions aimed at reducing fat intake on cancer outcomes has not been tested in the setting of large-scale clinical trials. Therefore, dietary change has not been uniformly recommended as part of the treatment strategy for men with prostate cancer.

A number of reports have evaluated the relationship between dietary factors and prognosis in men with prostate cancer [65,76-78]. One review suggested that soy intake or consuming a low-fat, vegan diet may have a favorable impact on prostate-specific antigen (PSA) or PSA doubling time [79]. Other studies suggest that high intake of saturated fat may be associated with worsened outcomes (eg, recurrence or PSA failure), while a plant-based diet could be linked to a lower risk of progression [78,80-82]. In one of these studies, higher BMI and higher intake of saturated fat were both independent predictors of biochemical failure, whereas total caloric intake was not associated with prognosis [82]. Other notable findings were that men who were both obese and consumed a diet high in saturated fat had the shortest biochemical failure-free survival (19 months), while those who were not obese and who consumed a diet low in saturated fat had the longest biochemical failure-free survival (46 months).

Several studies have looked at dietary interventions in prostate cancer survivors [79]. These studies have been unable to draw definitive conclusions and have instead focused on decreasing dietary fat and increasing intake of vegetables, tomatoes/lycopene, and soy products.

The Prostate Cancer Lifestyle Trial (PCLT) enrolled 93 patients with early stage low-grade cancer undergoing watchful waiting and then randomly assigned them to treatment with usual care (controls) or to a multifactorial intervention arm that included counseling and group-based support sessions designed to lower fat to 10 percent of total calories, consume a plant-based diet, increase exercise, and practice stress management. At one year, the multifactorial intervention decreased the PSA by 4 percent, while the PSA rose in 6 percent in those in the control arm. By two years of follow-up, 27 versus 5 percent of patients in the control and experimental arm, respectively, had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation) [83,84]. These differences were statistically significant.

Based on data from the Men's Eating and Living (MEAL) study (CALGB 70807), telephone-based dietary counseling for increased vegetable consumption did not reduce the risk of disease progression in men with prostate cancer. This randomized clinical trial was conducted in 478 men (aged 50 to 80 years) with biopsy-proven prostate adenocarcinoma (International Society of Urological Pathology grade group 1 in those <70 years and ≤2 in those ≥70 years). Tumors were stage cT2a or less, and serum PSA levels were less than 10 ng/mL. Patients were randomly assigned to a counseling behavioral intervention by telephone promoting consumption of seven or more daily vegetable servings or a control group, which received written information about diet and prostate cancer. At two-year follow-up, time to progression was similar between the two intervention groups (HR 0.96, 95% CI 0.75-1.24). [85].

Weight — Obesity is associated with worse outcomes among men at diagnosis with clinically localized prostate cancer. However, whether changes in weight following a diagnosis of prostate cancer can modify prognosis is unknown and is an area of active investigation.

As illustrated by the following studies, compared with leaner men, obese men are at a greater risk for:

More aggressive disease – A study of 1866 men undergoing prostate biopsy showed that the risk of a high-grade prostate cancer (ie, Gleason score ≥7) increased with an increasing BMI [86]. However, there was no relationship between BMI and incidence of lower-grade prostate cancer. In addition, data from the SELECT trial suggest that the relationship between BMI and aggressive prostate cancer at diagnosis varies by ethnicity [87]. Other data suggest a link between BMI at diagnosis and several molecular factors such as the presence of TMPRSS-ERG fusion and chromatin remodeling [88,89].

More advanced disease – A meta-analysis demonstrated a linear relationship between BMI and incidence of advanced prostate cancer (RR 1.09, 95% CI 1.02-1.16 for each 5 kg/m2 increase) and an inverse relationship between BMI and the development of localized prostate cancer (RR 0.94, 95% CI 0.91-0.94 for each 5 kg/m2 increase in BMI) [76].

Less responsive disease – A report of 287 men treated with radical prostatectomy followed by androgen deprivation therapy demonstrated an increased risk for distant metastasis and a nonsignificant trend toward an increased risk of prostate-specific mortality in men with a higher BMI [90].

Higher mortality – A meta-analysis of 22 reports demonstrated a 20 percent increase in the risk of prostate-specific mortality (RR 1.20, 95% CI 0.99-1.46) and a 21 percent increase in the risk of biochemical progression (RR 1.21, 95% CI 1.11-1.31) for each 5 kg/m2 increase in BMI [21].

By contrast, higher BMI may be associated with better overall survival in men with metastatic, castration-resistant prostate cancer [91-93].

Physical activity — There are limited data on the relationship between physical activity patterns and prostate cancer prognosis, although it remains an area of active interest. Two studies illustrate the potential benefits of exercise in this population:

In a study of 1455 men with localized prostate cancer, men who walked for at least three hours/week at a brisk pace had a 57 percent lower rate of disease progression compared with men who walked at an easy pace for less than three hours/week (HR 0.43, 95% CI 0.21-0.91) [94].

In a second report looking at physical activity patterns and outcomes in 2705 men taking part in the Health Professionals Follow-Up Study, men who walked for at least 90 minutes per week at a moderate-to-brisk pace had a 46 percent lower risk of all-cause mortality as compared with men who performed less or slower-paced walking (HR 0.51, 95% CI 0.36-0.72) [95].

One ongoing study, the INTERVAL trial, will test the impact of high-intensity interval training on overall survival in men with castrate-resistant metastatic prostate cancer, providing some of the first evidence regarding the potential risks and benefits of physical activity interventions in individuals with advanced cancer.

Colorectal cancer

Diet — Data suggest that dietary factors may influence outcomes in some patients with colorectal cancer (CRC). However, there are scant data on whether changes in diet after a diagnosis of CRC would be beneficial to CRC survivors. Furthermore, many CRC survivors do not adhere to dietary recommendations. As an example, 84 percent of survivors were not following the American Cancer Society recommendations regarding fruit and vegetable intake [96].

General dietary pattern — Observational studies of patients with colon cancer suggest that dietary pattern may affect prognosis [97-100]. For example:

In one study, the dietary status of 1009 patients with stage III colon cancer enrolled in a clinical trial was assessed at enrollment, four months after surgery (midway through eight months of adjuvant chemotherapy), and 14 months after surgery [97]. Outcomes were analyzed according to the extent to which patients followed both a "prudent" diet (high in fruits, vegetables, fish, poultry, whole grains) and a "Western-style" diet (increased amounts of red and processed meats, sweets, desserts, refined grains).

Compared with patients in the lowest quintile of Western diet consumption, those in the highest quintile had a greater risk of recurrence (HR 2.85, 95% CI 1.75-4.63) and death (HR 2.32, 95% CI 1.36-3.96) on multivariate analyses. By contrast, there were no differences in these outcomes between the highest and lowest quintile of the prudent dietary pattern. In a separate analysis from this study, patients in the highest quintile of dietary glycemic load had a higher risk of recurrence compared with those in the lowest quintile (HR for DFS 1.79, 95% CI 1.29-2.48) [98]. A higher glycemic load was also associated with worse DFS among overweight or obese participants (BMI ≥25 kg/m2; HR 2.26, 95% CI 1.53-3.32), but not in those patients with a lower BMI. In addition, higher total carbohydrate intakes were associated with lower DFS and overall survival.

In a separate study of 529 newly diagnosed CRC patients identified through a familial CRC registry, CRC patients with a high processed meat dietary pattern had worsened DFS (the highest versus the lowest quartile: HR 1.82, 95% CI 1.07-3.09). No associations were observed with the prudent-vegetable or the high-sugar patterns and DFS [99].

Although these analyses controlled for known factors that influence prognosis in CRC, these data should be interpreted cautiously because dietary differences may have antedated the diagnosis of cancer, influencing the subsequent natural history of disease.

Healthy diet in the general population, not specifically in cancer survivors, is discussed separately. (See "Healthy diet in adults".)

Specific dietary factors — Several specific dietary factors have been reported with associations to outcomes in CRC survivors. None have been studied in randomized trials to date. The mechanism associating these factors with CRC biology is not known, these factors have been associated with insulin regulation as well as inflammation, which may influence growth and spread of CRC cells. As these are initial reports and observational, it may be early to incorporate in clinical practice [98,101].

Coffee consumption – Although some evidence suggests that higher levels of coffee consumption may be associated with reduced cancer recurrence and death, causality is not established.

Stage III colon cancer – In one cohort of stage III (node-positive) colon cancer patients who participated in a trial comparing two different adjuvant chemotherapy regimens, patients consuming four or more cups per day of caffeinated coffee during and six months after adjuvant chemotherapy experienced a reduced cancer recurrence or mortality risk compared with abstainers (HR 0.48, 95% CI 0.25-0.91) [102]. The association persisted even after controlling for known or suspected predictors of patient outcomes, including physical activity, dietary glycemic load, and other dietary patterns. The authors postulated that coffee might reduce the risk of colon cancer recurrence and death through improved insulin sensitization and decreased hyperinsulinemia, on the basis of previous studies supporting the role of high-energy balance states in promoting colon cancer recurrence and mortality. However, it is possible that the observed association was related to confounding variables.

A beneficial impact of postdiagnosis coffee consumption was also reported in an analysis of data from the NHS and the Health Professionals Follow-up Study, which followed 1599 patients diagnosed with stage I to III CRC [103]. Higher total coffee intake was associated with reduced risk for both CRC-specific and all-cause mortality, with the strongest correlation among those with stage III CRC. Among these patients, every cup per day increase in total coffee intake was associated with an 18 percent lower risk of CRC-specific mortality (HR 0.82, 95% CI 0.68-1.0) and a 20 percent lower all-cause mortality (HR 0.80, 95% CI 0.68-0.91). By contrast, no association was found for patients with stage I or II CRC for either CRC-specific or all-cause mortality.

Metastatic colon cancer – Data also suggest an association between coffee (both caffeinated and decaffeinated) and survival in patients with advanced colorectal cancer. As an example, in a prospective observational cohort study of 1171 patients with treatment-naïve metastatic CRC who participated in a randomized trial of different chemotherapy and biological therapy combinations, increased consumption of coffee was associated with decreased risk of cancer progression (HR for 1 cup/day increment 0.95, 95% CI 0.91-1.00) and death (HR for 1 cup/day increment 0.93, 95% CI 0.89-0.98) [104]. Compared with participants who did not drink coffee, the study also demonstrated improved OS for those who consumed two to three (HR 0.82, 95% CI 0.67-1.00) and four or more cups of coffee per day (HR 0.64, 95% CI 0.46-0.87).

Fiber intake – A benefit for higher postdiagnosis fiber intake on CRC outcomes was suggested in a study of 1575 health care professionals with stage I to III CRC who were derived from two cohorts, the NHS and Health Professionals Follow-Up Study [105]. Patients who increased their fiber intake after diagnosis had a lower mortality, and each 5-g/day increase in intake was associated with a 19 percent lower CRC-specific mortality (95% CI 7 to 28 percent), and a 14 percent reduction in all-cause mortality (95% CI 8 to 19 percent). Notably, increased intake of cereal fiber was associated with both CRC-specific and all-cause mortality, while no association was found for fruit fiber.

Despite these data, there have been no randomized trials that have tested the impact of dietary interventions in individuals with early stage CRC.

Nuts – Diets rich in nuts may be associated with reduced rates of cancer recurrence and death in patients with stage III colon cancer. In a prospective, observational study of 826 patients with stage III colon cancer who reported dietary intake on food frequency questionnaires, those who consumed two or more servings of nuts per week experienced improved DFS (HR 0.58, 95% CI 0.37-0.92) and overall survival (HR 0.43, 95% CI 0.25-0.74) relative to those who consumed fewer than two servings of nuts per week [106]. In exploratory multivariate analyses of DFS adjusting for disease, treatment, and patient characteristics, nonsignificant trends towards improved DFS were observed with higher total nut intake, but statistical power to detect differences was limited by small sample size.

Glycemic load, carbohydrates, and sugar-sweetened beverages – Glycemic load, carbohydrates, and sugar-sweetened beverages are dietary measures associated with insulin resistance. Higher dietary glycemic load and total carbohydrate intake were associated with an increased risk of recurrence and mortality in an observational study of 1011 stage III colon cancer patients with stage III colon cancer treated with adjuvant chemotherapy trial [98]. Patients in the highest quintile of dietary glycemic load experienced worsened disease-free survival (DFS; HR 1.79, 95% CI 1.29-2.48) compared with those in the lowest quintile. Similarly, patients in the highest quintile of carbohydrate intake also experienced worsened DFS (HR 1.73, 95% CI 1.22-2.46) compared with those in the lowest quintile.

In another observational study of 1201 women in the NHS with nonmetastatic CRC, a higher combined postdiagnosis intake of sugar-sweetened beverages and fruit juices was associated with worsened overall mortality (HR for each additional serving 1.11, 95% CI 1.01-1.23) [107].

Weight — Increasing BMI, particularly obesity, has been associated with an increased risk of multiple obesity-associated cancers, including CRC [108]. However, BMI may have a paradoxical association with survival in patients with colon cancer, particularly those with BMI in the 25 to 32 kg/m2 range. Furthermore, whether purposeful weight loss provides a benefit in survival outcomes related to CRC is unknown. As such, until there is better understanding of what and how to counsel regarding BMI, as well as potential incorporation of body composition, we do not advise weight loss as a means to prevent recurrence.

In an analysis including 12,000 CRC survivors, those who were overweight had a greater risk of a obesity-related secondary cancers (HR 1.39, 95% CI 1.01-1.92), as did those who were obese (HR 1.47, 95% CI 1.02-2.12), relative to those with a normal BMI. These data suggest that obesity contributed to the elevated cancer risks rather than increased genetic susceptibility. Therefore, they support obesity as a risk factor for both primary and secondary obesity-related malignancies in this population.

In the Cancer Prevention Study-II Nutrition study, patients diagnosed with non-metastatic CRC who had a high prediagnosis BMI ≥30 kg/m2 had poorer overall, cancer-specific, and cardiovascular-specific survival relative to those with a normal BMI [109]. However, there was no association between postdiagnosis BMI and outcomes, which is consistent with the findings of at least one other study [110]. By contrast, another study demonstrated that stage II and III colon cancer patients with BMI >35 kg/m2 after surgery had a statistically significant 38 percent worse DFS compared with normal-weight patients (BMI 18.5 to 24.9 kg/m2) [111].

A population-based cohort of 3408 patients with stage I to III CRC suggested a U-shaped relationship between BMI and outcomes in CRC survivors [112]. Patients who were underweight at diagnosis (BMI <18.5 kg/m2) and those who were class II or III obese (BMI ≥35 kg/m2) had a worse all-cause mortality, compared with patients who were low-normal weight (BMI 18.5 to <23 kg/m2). By contrast, patients who were high-normal weight (BMI 23 to <25 kg/m2), low-overweight (BMI 25 to <28 kg/m2), and high-overweight (BMI 28 to <30 kg/m2) had lower mortality risks. Finally, patients who were class I obese (BMI 30 to <35 kg/m2) showed no difference in risk. These data raise the question of optimal weight in this population.

BMI does not reflect muscle or fat distribution, and there are increasing data supportive of a protective effect of muscle for cancer patients [113-115]. One explanation for the U-shaped curve and possible protective effect of being overweight (BMI 25 to <30 kg/m2) relates to body composition. As an example, in a pooled analysis of 44 observational studies that included 18,891 patients with CRC, over one-third of patients (37 percent) were found to be sarcopenic (ie, low muscle mass) around the time of diagnosis [116]. After CRC surgery, sarcopenia was associated with a higher risk of total postoperative complications (OR 1.84, 95% CI 1.35-2.49), such as postoperative severe complications; postoperative mortality; postoperative infections, and postoperative cardiopulmonary complications. Sarcopenic patients also had lower overall survival (HR 1.83, 95% CI 1.57-2.14) and cancer-specific survival (HR 1.77, 95% CI 1.40-2.23) compared with nonsarcopenic patients.

Physical activity — Higher levels of physical activity may reduce CRC-specific and overall mortality [117], in addition to having a beneficial impact on fatigue, QOL, and functional status [118-122].

A systematic review included six studies conducted in CRC survivors [117]. All examined leisure-time activity, and all but one adjusted for stage, CRC risk factors, and BMI. Three studies found that higher levels of physical activity after diagnosis were associated with a reduced risk of CRC-specific mortality, ranging from 43 to 61 percent. In addition, all five studies that examined physical activity after a diagnosis of CRC found that postdiagnosis activity was associated with reduced risks of death from any cause; four were statistically significant.

Despite these findings, some data suggest that CRC survivors do not adhere to physical activity guidelines. As an example, 65 percent of CRC survivors were not following recommendations for physical activity proposed by the American Cancer Society [96]. The ongoing Colon Health and Lifelong Exercise Change (CHALLENGE) study will evaluate the impact of exercise on disease outcomes for CRC survivors [123].

Endometrial cancer

Weight — Although obesity is associated with less aggressive histologic types of endometrial cancer [124], it is associated with an increased risk of death [13,124]. As in other cancer types, whether purposeful weight loss after endometrial cancer can improve outcomes is unknown and is a topic of continued investigation.

It is well documented that most women with type I endometrial cancer will not die of their disease; rather, they will die of intercurrent medical illnesses, many of which are also related to obesity [125]. Further, there is evidence that obesity may play a role in endometrial cancer prognosis. Specifically:

Obesity was associated with a higher risk for recurrent endometrial cancer and other malignancies when compared with women of normal weight [13].

Endometrial cancer survivors with obesity and diabetes have a decreased life expectancy when compared with their nonobese, nondiabetic counterparts with the same malignancy [126,127].

Compared with those with a BMI <25 kg/m2, the relative risk of death for obese endometrial cancer patients with BMI of 30 to 34 kg/m2 is 2.53 (95% CI 2.02-3.18) and for BMI >40 kg/m2, 6.25 (95% CI 3.75-10.42) [13].

Unfortunately, endometrial cancer survivors have a high prevalence of continued obesity after treatment has completed [128]. In addition, obese cancer survivors may be less likely to adopt weight loss or healthier lifestyle modifications [129], including the adoption of physical activity [130]. Underlining the complexity of weight change after cancer diagnosis and treatment, one study suggests that an increase or decrease in BMI after therapy may be adversely associated with mortality [131].

Beyond prognosis, studies in endometrial cancer survivors suggest that increasing obesity is associated with lower health-related QOL and is inversely correlated with lower functional domain scores, including lack of fulfillment in work and enjoyment of life [132]. A large population-based study from the Netherlands showed that increasing BMI is related to several QOL outcomes, including decreased vitality, fatigue, and more symptoms associated with lymphedema [133].

Efforts to increase physical activity and address obesity in these patients may be challenging for various reasons, including the presence of other medical conditions that might interfere with an increased active lifestyle, including arthritis, knee pain, and back pain [130]. Nonetheless, if the cancer diagnosis is indeed a "teachable moment," there is an opportunity to change behaviors [134-136].

Physical activity — Whether physical activity improves cancer-specific outcomes in women with endometrial cancer is unknown [137-140]. However, data from observational studies and a randomized trial have demonstrated that an exercise intervention is feasible in this population [141].

In the Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED) study, women with a BMI ≥25 kg/m2 were randomly assigned to a lifestyle intervention (consisting of a six-month education and counseling session) or to usual care [141]. Adherence to the intervention arm was 84 percent. In addition, women in the intervention arm reported greater endurance measured by physical activity minutes compared with women in the usual care group (mean difference of 89 minutes at 12 months). Whether changes in activity of this magnitude would have impact on survival outcomes requires further follow-up.

CLINICAL LIFESTYLE RECOMMENDATIONS FOR CANCER SURVIVORS — Given the growing body of evidence that exercise, diet, and weight management are important in cancer prevention and control, a number of groups, including the American Cancer Society, the American College of Sports Medicine [29], the Clinical Oncology Society of Australia [142], and the European Society for Medical Oncology [143], have developed nutrition and physical activity guidelines for cancer survivors based on the available evidence linking diet, weight, and physical activity to cancer outcomes [24,27-29,90]. Although recommendations have some individual differences, they broadly recommend the following:

Maintain a healthy weight and attempt weight loss if overweight or obese.

Engage in a physically active lifestyle, ideally consisting of at least 150 minutes of moderate-intensity (or 75 minutes of vigorous) physical activity per week plus two resistance training sessions.

Notably, the ACSM guideline also suggests that lower levels of physical activity (eg, 30 minutes of moderate-intensity aerobic physical activity three times per week or aerobic and resistance training two to three times per week) can also lead to improvements in patient-reported outcomes and fitness in cancer survivors. (See 'Exercise and outcomes in cancer survivors' above.)

Consume a healthy diet, with at least five servings of fruits and vegetables per day and limited ingestion of processed foods and red meats.

Limit alcohol to no more than one drink/day for women and two drinks/day for men. (See "Overview of the risks and benefits of alcohol consumption".)

SUMMARY AND RECOMMENDATIONS

Improving health-related outcomes in cancer survivors – Novel methods to improve outcomes in cancer survivors may offer attractive additions to the currently available treatment options, especially those that are also associated with improvements in quality of life (QOL) and other health benefits. (See 'Introduction' above.)

Energy balance factors – Diet, physical activity, and weight are collectively considered energy balance factors because they describe the relationship between energy consumed (diet), energy expended (physical activity), and energy stored (adiposity). They have each been linked to cancer outcomes. (See 'Energy balance in cancer' above.)

Dietary intake – Dietary intakes have been linked to outcomes in some cancers. However, there are few randomized trials testing the impact of dietary change on cancer outcomes. (See 'Breast cancer' above and 'Prostate cancer' above and 'Colorectal cancer' above and 'Endometrial cancer' above.)

Obesity and weight loss – Obesity (defined as a body mass index [BMI] >30 kg/m2) at diagnosis is also associated with an increased mortality risk in patients with early stage breast cancer and in endometrial cancer, and potentially in those with prostate cancer or colorectal cancer (for those with BMI >35 kg/m2). Whether purposeful weight loss after cancer diagnosis can improve outcomes is unknown and is a topic of continued investigation. (See 'Breast cancer' above and 'Prostate cancer' above and 'Colorectal cancer' above and 'Endometrial cancer' above.)

Physical activity – Observational studies have shown an association between physical activity patterns after cancer diagnosis and prognosis in individuals diagnosed with early-stage cancers of the breast, colon, and prostate. However, there are limited data from randomized trials evaluating the impact of increased physical activity on rates of cancer recurrence or mortality. (See 'Physical activity' above.)

Exercise and outcomes in cancer survivors – Multiple interventional studies have evaluated the safety, feasibility, and benefits of exercise in cancer survivors. The benefits include a reduction in fatigue, improvement in QOL, and improvements in fitness and physical functioning. (See 'Exercise and outcomes in cancer survivors' above.)

Lifestyle recommendations for diet, physical activity, and body weight in cancer survivors – Although limited trial data are available on the effects of interventions aimed at dietary modification, increasing physical activity, and weight loss among cancer survivors, we agree with guidelines for cancer survivors from the American Cancer Society, the American College of Sports Medicine, and other groups that recommend maintaining a healthy weight, adopting a physically active lifestyle, and eating a healthy diet rich in plant sources. (See 'Clinical lifestyle recommendations for cancer survivors' above.)

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Topic 14222 Version 40.0

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