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

INTRODUCTION — 

With advances in early detection and treatments for cancer, there were over 43 million people alive globally with a history of cancer in 2018 [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 females", 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 [2-7]. 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 [8].

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 minimize disease and treatment-related side effects for cancer survivors [3,9-12]. Some preliminary evidence suggests that lifestyle change may also improve prognosis in individuals with early stage cancers [13,14], but evidence is mixed [15,16], and 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 [17]. 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.)

The American Society of Clinical Oncology developed a guideline focused on patients receiving chemotherapy and radiation, as well as those in the perioperative period [12]. The guideline panel reviewed data from systematic reviews (nine on diet and one on weight management), as well as randomized clinical trials. The guideline panel recommended against the use of neutropenic diets in patients with cancer (in particular those that omit fresh fruits and vegetables), including in patients undergoing treatment for hematologic malignancies, but lack of evidence prevented further recommendations regarding dietary changes or weight loss or weight maintenance interventions during cancer treatment.

There are no randomized data evaluating the impact of dietary change on cancer outcomes. However, a meta-analysis of 117 cohort studies which enrolled 209,597 cancer survivors, found 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 [18].

The role of specific dietary regimens as a complementary or alternative treatment for cancer is discussed separately. (See "Overview of complementary, alternative, and integrative medicine practices in oncology care, and potential risks and harm".)

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 [19-25]. As rates of obesity rise across the world, obesity contributes to an increasing proportion of new cancer cases. Estimates suggest that 4 to 8 percent of cancer cases worldwide are directly attributable to obesity, with the proportion of cancer cases related to obesity varying considerably between low- and high-income countries [26-28]. In the United States, obesity is estimated to cause approximately 4.7 percent of cancer cases in males and 9.6 percent in females, with approximately 50 percent of cancers of the liver, gallbladder, and endometrium attributable to obesity [26,29].

A number of studies have also linked obesity to an increased risk of cancer recurrence and mortality [7,8,30-32]. A meta-analysis of 203 studies that included over 6 million patients, evaluated the relationship of obesity with cancer outcomes in patients with early-stage and advanced solid tumors [32]. In this study obesity was associated with an increased risk of overall (hazard ratio [HR] 1.14, 95% CI 1.09-1.19) and cancer-specific mortality (HR 1.17, 95% CI 1.12-1.23). There was also an increased risk of cancer recurrence in individuals with early-stage disease (HR 1.13, 95% CI 1.07-1.19). Notably, the relationship between obesity and reduced overall survival was most pronounced in individuals with cancers of the breast, colorectum, and uterus. Obesity was associated with worse cancer-specific survival in breast, colorectal, prostate, and pancreatic cancer. However, obesity was associated with better overall survival in individuals with lung cancer, renal cell carcinoma, and melanoma.

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 [33]. The Initiative focused 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.

Activity level

Physical activity — Physical activity has been associated with both decreased cancer risk and cancer mortality. Exercise is a subset of physical activity that is planned, structured, and repetitive with the intention to improve or maintain physical fitness [34].The 2018 Physical Activity Guidelines Advisory Committee reviewed 45 meta-analyses, systematic reviews, and pooled analyses evaluating the relationship between physical activity and cancer risk and found strong evidence for an association between higher levels of physical activity and lower risk of cancers of the bladder, breast, colon, endometrium, esophagus (adenocarcinoma), kidney, and stomach. Relative risk reductions of 10 to 20 percent were seen in the most active individuals compared with the least active [35,36]. Additionally, 18 reports identified by the committee evaluated the relationship between physical activity and cancer survival. Systematic reviews and meta-analyses were available only for breast, colorectal, and prostate cancers. In these malignancies, higher levels of physical activity were associated with a reduced risk of cancer-specific and all-cause mortality, with relative risk reductions up to 40 to 50 percent.

The American Society of Clinical Oncology developed a guideline focused on physical activity for patients receiving therapy for cancer [12]. The guideline panel reviewed data from 52 systematic reviews (42 focused on exercise) as well as additional randomized clinical trials. Key guideline recommendations included a recommendation for regular aerobic and/or resistance exercise during chemotherapy and/or radiation for malignancies being treated for curative intent and a recommendation for exercise in the perioperative period for patients undergoing surgery for lung cancer. The literature review demonstrated moderate-quality evidence that exercise during chemotherapy and/or radiation led to reductions in fatigue, as well as preservation of cardiorespiratory fitness, physical function, and strength. In some populations, exercise during this period also led to improvements in quality of life and reductions in anxiety and depression. Additionally, low-quality evidence demonstrated that exercise during the perioperative period led to reduced length of stay and postoperative complications in patients with lung cancer. Finally, exercise was found to be safe in both the setting of chemotherapy/radiation and in the postoperative period, with a low risk of adverse events.

Sedentary behavior — 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 [37,38]. 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) [37]. Some cancer survivors may benefit from physical activity [39] and exercise rehabilitation to prevent or mitigate such risks. (See "Physical rehabilitation for cancer survivors", section on 'Cardiotoxicity'.)

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

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 females with breast cancer at this time.

Many observational studies have evaluated relationships between breast cancer outcomes, such as recurrence and mortality, and 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]. Overall, 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.

The World Cancer Research Fund Continuous Update project conducted a systematic review of randomized controlled trials and longitudinal observational studies evaluating the relationship between postdiagnosis dietary factors and breast cancer outcomes in 2022 [41,42]. This review of over 150,000 patients with breast cancer evaluated the relationships between breast cancer outcomes and intake of fruits, soy foods, carbohydrates, proteins, fats, fiber, and alcohol. Results are summarized below:

●Health dietary patterns – Limited-evidence from 12 observational studies suggest that a predefined "healthy" dietary pattern was associated with a lower risk of all-cause mortality but not breast cancer-specific mortality.

●Soy food intake – Limited evidence from five observational studies suggested that increased soy intake was associated with a nonsignificant decrease in all-cause and breast cancer-specific mortality. Additionally, a pooled analysis of two United States and one Chinese cohort suggested an inverse relationship between soy intake and breast cancer recurrence.

●Dietary fiber intake – Limited evidence from four observational studies suggested a relationship between higher fiber intake and a lower risk of all-cause mortality.

●Alcohol – No relationship between alcohol intake and all-cause or breast cancer-specific mortality was seen in 22 observational studies. Alcohol intake was also not associated with the risk of breast cancer recurrence. One of three studies evaluating the risk of postdiagnosis alcohol intake and second cancers showed an elevated risk for increasing alcohol intake.

●No consistent relationships were seen between breast cancer outcomes and intake of fats, fruits, vegetables, whole grains, red and processed meats, fish, eggs, milk, dairy products, or supplements.

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 females with stages I to IIIa breast cancer to a low-fat dietary intervention or usual care control group [13]. 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 [13]. 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, females with stages I to IIIa breast cancer were randomly assigned to low-fat, high-fruit and vegetable diet or to a control group [15]. 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 females (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 females", section on 'Low-fat dietary pattern in postmenopausal females'.)

Weight — Obesity at diagnosis is 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 is an established risk factor for poor prognosis in early-stage breast cancer. A 2022 systematic review and meta-analysis of studies evaluating the relationship between obesity and breast cancer prognosis conducted by the Global Cancer Update Program, including 225 observational studies and one randomized controlled trial, concluded that there was strong evidence that postdiagnosis body mass index (BMI) was associated with increased all-cause mortality, with each 5 kg/m² increase in BMI associated with a 7 percent increase in the risk of mortality [7]. Additionally, higher BMI was also associated with an increased risk of breast cancer-specific mortality and increased risk of second primary breast cancer, with each 5 kg/m² in BMI associated with a 10 percent increase in breast cancer-specific mortality and a 14 percent increase in the risk of second breast cancer. Other reviews and meta-analyses evaluating the relationship between postdiagnosis BMI and breast cancer outcomes have demonstrated that the increased risk of mortality associated with increased BMI was seen in both pre- and postmenopausal females [43] and across various breast cancer subtypes [44].

Notably, obesity has also been linked to poor outcomes in the setting of clinical trials of chemotherapy, endocrine therapy, and human epidermal growth factor 2 (HER2)-targeted therapy, demonstrating the relationship between obesity and prognosis across breast cancer subtypes and in the setting of modern treatment paradigms. As examples of these data:

●A meta-analysis presented by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) including 80,000 females in 70 different adjuvant trials demonstrated a 5 percent absolute increase in mortality in premenopausal females with hormone receptor-positive disease with obesity versus those with a normal BMI [45].

●In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial, females who had a body mass index (BMI) ≥35 kg/m² had a 60 percent higher risk of recurrence as compared with females with a BMI <25 kg/m² [46]. A similar result was noted among premenopausal females with obesity treated with ovarian suppression and anastrozole in the Austrian Breast Cancer Study Group 12 (ABCSG-12) study [47]. However, studies have not suggested an increased risk of cancer-related or overall mortality in patients with obesity treated with tamoxifen, suggesting the relationship between BMI and breast cancer outcomes may vary across different types of endocrine therapy [48]. Notably, in the BIG-198 trial and other studies, the benefits of aromatase inhibitors over tamoxifen persisted across BMI categories [49]. (See "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Obese women'.)

●Females with obesity and 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 females [50]. Similar findings were seen in CALGB 9741 in patients treated with dose-dense doxorubicin, cyclophosphamide, and a taxane [51]. (See "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer", section on 'Obese women'.)

●A meta-analysis of 13 observational and interventional studies of females with HER2-positive breast cancer demonstrated that obesity at diagnosis was associated with an increased risk of disease recurrence and mortality [44].

The etiology of the poor outcomes seen in females with obesity and early 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 patients with obesity due to fears of increased toxicity. Studies subsequently demonstrated that these practices resulted in inferior outcomes [52,53], leading the American Society of Clinical Oncology to develop guidelines recommending the use of full, weight-based doses of chemotherapy for individuals with obesity. This topic is discussed separately. (See "Dosing of anticancer agents in adults", section on 'Dosing for patients with obesity and who are overweight'.)

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 [54]. A meta-analysis of 12 studies, including 23,832 females with early breast cancer, demonstrated that weight gain of ≥5 percent of baseline body weight after diagnosis was associated with an increased risk of all-cause, but not breast cancer-specific, mortality [55].

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 [56,57].

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 [10,58-63]. However, it is unclear if weight loss leads to a decrease in the risk of recurrence and associated mortality. More research and longer-term follow-up is needed to answer this question. Examples of studies which examine the role of weight loss in breast cancer survivors are as follows:

●The Lifestyle Intervention Study for Adjuvant Treatment of Early Breast Cancer (LISA) randomly assigned 338 postmenopausal females with hormone receptor-positive breast cancer to a two-year telephone-based weight loss intervention or to usual care [10]. LISA demonstrated that females 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 [10]. Long-term follow-up demonstrated that females 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 [14].

●The SUCCESS C trial was a phase III trial comparing an anthracycline-based chemotherapy regimen to an anthracycline-sparing regimen in females with stage II to III, HER2-negative breast cancer. A total of 2292 females with a BMI between 24 and 40 kg/m² underwent a second randomization to a two-year lifestyle intervention versus a control group. Preliminary findings from the trial did not demonstrate benefit from the lifestyle intervention; 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 [64]. However the 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.

●The Italian Diet and Androgens (DIANA)-5 trial tests the impact of a Mediterranean, macrobiotic diet in combination with increased physical activity on breast cancer outcomes and serum biomarkers in females with early breast cancer [65]. The study enrolled 1542 females with early breast cancer and metabolic syndrome or other metabolic risk factors [66]. In the 1344 females who completed the first year of the intervention, those randomized to the diet and exercise intervention experienced significantly more favorable changes in anthropometric and dietary measures as compared to individuals randomized to control. Cancer outcomes are still pending.

●The Breast cancer WEight Loss (BWEL) trial is a phase III randomized, controlled trial designed to test the impact of a two-year telephone-based weight loss intervention on invasive DFS in females who are overweight and obese with stage II to III breast cancer [67]. The study enrolled 3180 females from more than 600 centers across the United States and Canada, including 25 percent racial and ethnic underrepresented groups [68]. Preliminary data demonstrates that females randomized to the weight loss intervention lost an average of 5.7 percent of baseline body weight versus controls at one-year, with significant weight loss in females randomized to the weight loss intervention across patient and tumor characteristics. Cancer outcomes are still pending.

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 [69]. Data from observational studies show that females who participate in a moderate amount of physical activity after diagnosis have improved outcomes as compared with less active females [2,5,70-73]. 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.

The 2018 Physical Activity Guidelines Advisory Scientific Report and subsequent systematic review identified six meta-analyses evaluating the relationship between postdiagnosis physical activity and breast cancer prognosis and concluded that there was consistent evidence for an inverse relationship between increasing levels of physical activity and lower risk of all-cause and breast cancer-specific mortality in individuals with early-stage breast cancer [35]. 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 [74].

Numerous randomized trials have tested the feasibility and potential benefits of increasing exercise after diagnosis in breast cancer patients [75-82]. 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 'Physical activity' above.)

The impact of upper body strength training on symptoms, such as lymphedema, is discussed separately. (See "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 males 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 males with prostate cancer.

A number of reports have evaluated the relationship between dietary factors and prognosis in males with prostate cancer [69,83-85]. 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 [86]. 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 [85,87-89]. 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 [89]. Other notable findings were that males 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 [86]. 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) [90,91]. 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 males with prostate cancer. This randomized clinical trial was conducted in 478 males (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). [16].

Weight — Obesity is associated with worse outcomes among males 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 males, obese males are at a greater risk for:

●More aggressive disease – A study of 1866 males undergoing prostate biopsy showed that the risk of a high-grade prostate cancer (ie, Gleason score ≥7) increased with an increasing BMI [92]. 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 [93]. Other data suggest a link between BMI at diagnosis and several molecular factors such as the presence of TMPRSS-ERG fusion and chromatin remodeling [94,95].

●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) [83].

●Less responsive disease – A report of 287 males 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 males with a higher BMI [96].

●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 [31].

By contrast, higher BMI may be associated with better overall survival in males with metastatic, castration-resistant prostate cancer [97-99]. However, other studies, including cohort analysis of postsurgical BMI from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study of males who underwent radical prostatectomy, did not find an association when adjusting for disease severity factors [100].

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 males with localized prostate cancer, males who walked for at least three hours/week at a brisk pace had a 57 percent lower rate of disease progression compared with males who walked at an easy pace for less than three hours/week (HR 0.43, 95% CI 0.21-0.91) [101].

●In a second report looking at physical activity patterns and outcomes in 2705 males taking part in the Health Professionals Follow-Up Study, males 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 males who performed less or slower-paced walking (HR 0.51, 95% CI 0.36-0.72) [102].

One ongoing study, the INTERVAL trial, will test the impact of high-intensity interval training on overall survival in males 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 [103].

General dietary pattern — Observational studies of patients with colon cancer suggest that dietary pattern may affect prognosis [104-107]. 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 [104]. 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) [105]. 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 [106].

●One study found 30 percent lower colorectal cancer mortality and 21 percent lower all-cause mortality with an optimal prediagnosis diet, as determined by the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) dietary score (which evaluates diet based on consumption of whole grains, vegetables, fruits, beans, energy-dense foods, sugary drinks, red and processed meats, and alcohol) [108].

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 [109]. As these are initial reports and observational, it may be early to incorporate in clinical practice [105,110].

●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) [111]. 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 [112]. 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) [113]. 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 [114]. 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 [115]. 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 [105]. 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 females 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) [116].

Weight — Increasing BMI, particularly obesity, has been associated with an increased risk of multiple obesity-associated cancers, including CRC [117]. 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 [118]. However, there was no association between postdiagnosis BMI and outcomes, which is consistent with the findings of at least one other study [119]. 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) [120].

●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 [121]. 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 [122-124]. 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 [125]. 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 [126,127], in addition to having a beneficial impact on fatigue, QOL, and functional status [128-132].

A systematic review and meta-analysis of 18 prospective cohort studies in over 31,000 CRC survivors demonstrated that the highest versus the lowest levels of prediagnosis physical activity were associated with decreased risk of total mortality (HR 0.81, 95% CI 0.76-0.87) and CRC-specific mortality (HR 0.85, 95% CI 0.77-0.98), respectively. Risk reductions were also demonstrated for postdiagnosis physical activity (HR 0.63, 95% CI 0.54-0.74 for total mortality; and HR 0.64, 95% CI 0.47-0.88 for CRC-specific mortality). The inverse association between prediagnosis physical activity and mortality was more pronounced for colon cancer than that for rectal cancer [133].

Sedentary behavior has also been consistently shown to be associated with poorer outcomes in CRC survivors. A meta-analysis of three prospective cohort studies, inclusive of 6791 CRC survivors, demonstrated a significantly increased association in the risk CRC-specific mortality (HR 1.53; 95% CI 1.14-2.06) among those who reported more versus less sedentary behavior [134].

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 [103]. The ongoing Colon Health and Lifelong Exercise Change (CHALLENGE) study will evaluate the impact of exercise on disease outcomes for CRC survivors [135].

Endometrial cancer

Weight — Although obesity is associated with less aggressive histologic types of endometrial cancer [136], it is associated with an increased risk of death [19,136]. 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 females with nonaggressive endometrial cancer will not die of their disease; rather, they will die of intercurrent medical illnesses, many of which are also related to obesity [137]. 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 females of normal weight [19].

●Endometrial cancer survivors with obesity and diabetes have a decreased life expectancy when compared with their nonobese, nondiabetic counterparts with the same malignancy [138,139].

●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) [19].

Unfortunately, endometrial cancer survivors have a high prevalence of continued obesity after treatment has completed [140]. In addition, obese cancer survivors may be less likely to adopt weight loss or healthier lifestyle modifications [141], including the adoption of physical activity [142]. 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 [143].

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 [144]. 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 [145].

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 [142]. Nonetheless, if the cancer diagnosis is indeed a "teachable moment," there is an opportunity to change behaviors [146-148].

A Cochrane review of 12 randomized controlled trials in females with endometrial cancer who were overweight or obese and undergoing current or previous treatment compared lifestyle and behavioral interventions to facilitate weight loss with usual care. While the follow-up was short for most trials, there was no improvement in overall survival or cancer-specific survival. However, the combined behavior and lifestyle intervention was not associated with significant weight loss at either 6 or 12 months [149].

Physical activity — Whether physical activity improves cancer-specific outcomes in females with endometrial cancer is unknown [150-153]. However, data from observational studies and a randomized trial have demonstrated that an exercise intervention is feasible in this population [154].

In the Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED) study, females 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 [154]. Adherence to the intervention arm was 84 percent. In addition, females in the intervention arm reported greater endurance measured by physical activity minutes compared with females 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 [76], the Clinical Oncology Society of Australia [155], and the European Society for Medical Oncology [156], have developed nutrition and physical activity guidelines for cancer survivors based on the available evidence linking diet, weight, and physical activity to cancer outcomes [11,75,76,96,157]. 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 'Physical activity' 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 females and two drinks/day for males. (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 'Physical activity' 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.)