SAN FRANCISCO—It is widely appreciated that lifestyle choices can affect the likelihood that an individual will develop colorectal cancer. Now a growing body of data show that lifestyle choices after a diagnosis of colorectal cancer are associated with the risk of disease recurrence and death, researchers reported here at the Gastrointestinal Cancers Symposium. The meeting is cosponsored by the American Gastroenterological Association Institute, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
“This information is incredibly important,” said Jennifer C. Obel, MD, a member of ASCO's Communications Committee, who is Attending Physician and Assistant Professor at the NorthShore University Health System in Evanston, IL, who was not involved in the studies. “I think what our patients most care about is ‘What can I do to improve my health?’ This is something they can do.”
Pointing to the details of the work presented by Jeffrey Meyerhardt, MD, MPH, Assistant Professor of Medicine at Brigham and Women's Hospital and Dana-Farber Cancer Institute, Dr. Obel continued, “He found that patients who walked at a moderate pace for one hour six days a week had a 50% decreased risk of having recurrent colon cancer. That is a very important clinical finding.”
Leonard Saltz, MD, Attending Physician at Memorial Sloan-Kettering Cancer Center in New York, who was a coauthor on some of the studies, said in an interview that he was surprised these data had panned out: “I thought that for people who don't have cancer that modifying diet and exercise would make a difference. But what Jeff's data say is that good diet and good exercise improve the body's ability to eradicate small-volume disease.”
Explaining further, he noted that disease recurrence occurs due to regrowth of tumor cells left behind after surgery and chemotherapy. The fact that physical exercise and a moderate diet were associated with a reduced risk of recurrence and death suggest that a well-fed, exercised body is actually better able to protect itself against those remaining cells than a sedentary one with a poorer diet is—“That is kind of interesting,” Dr. Saltz said.
Six Hours a Week
Dr. Meyerhardt presented observational data gathered from several sources, including a prospective companion study that enrolled individuals who were already participating in a randomized controlled Cancer and Leukemia Group B trial. In that study, CALGB 89803, patients with Stage III colorectal cancer were assigned to weekly fluorouracil and leucovorin with or without irinotecan. (Primary results from the trial showed no benefit with the addition of irinotecan.)
To begin to understand the impact of post-diagnosis diet and physical activity on the risk of recurrence and overall survival, Charles Fuchs, MD, Director of the Gastrointestinal Malignancies Program at Dana-Farber, designed the prospective companion study in which patients completed questionnaires three months after starting chemotherapy and six months after completing chemotherapy. Of 1,177 patients eligible for the companion study, 832 completed both questionnaires.
Even modest amounts of regular physical activity had a significant impact on the risk of recurrence, with the magnitude of benefit increasing with increasing activity up to 18 metabolic equivalent task hours (MET-hours) per week.
People who reported as little as three MET-hours a week—which is equivalent to one hour of walking at a moderate pace of two to three miles a hour, had an approximately 10% drop in their risk of recurrence, relative to those who had less than 3 MET-hours a week. That reduction in risk climbed to 50% for individuals who reported 18 MET-hours per week, which was equivalent to six hours of walking at a moderate pace during the week. Additional exercise above that amount was not associated with a further reduction in risk of recurrence.
Physical activity was also associated with substantial gains in overall survival. People who participated in 3 to 8.9 MET-hours of physical activity a week had a 15% reduction in risk of death relative to those reporting less than three MET-hours.
Improvements in survival increased with increasing activity up to 27 MET-hours a week, with individuals reporting between 9 and 26.9 MET-hours a week showing a 29% reduction in the risk of death and those above 27 MET-hours gaining a 69% risk reduction.
“These results were consistent whether you looked at body mass index [BMI], gender, number of positive lymph nodes, treatment arm, age, and baseline performance status,” Dr. Meyerhardt said.
Nurses' Health Study
To validate this observation, Dr. Meyerhardt and colleagues turned to the Nurses' Health Study, the longitudinal cohort study of 121,000 nurses that was started in the 1970s. Participants complete questionnaires every two years, including data on physical activity and diet, and remain in the study even after a cancer diagnosis.
Examining data from 573 women who were diagnosed with Stage I-III colorectal cancer, the investigators found that women who engaged in 18 MET-hours of physical activity a week or more had a 61% reduction in risk of disease-specific mortality and a 52% reduction in all-cause mortality relative to individuals who reported less than three MET-hours per week, after adjusting for tumor stage, the number of positive lymph nodes, and other known risk factors.
When the researchers examined the pre-diagnosis activity for these women, they found that increasing physical activity did not affect colorectal cancer-specific mortality. “That implies that the physical activity after diagnosis was more important towards prognosis,” Dr. Meyerhardt said.
Moderate Diet Lowers Risk, Weight Loss Does Not
Dr. Meyerhardt and colleagues also examined the impact of post-diagnosis diet on clinical outcomes, focusing on diet patterns rather than individual food items. The two patterns they considered were a Western pattern diet, which is characterized by a higher intake of red meat, processed meat, refined grains, sweets, desserts, French fries, and high-fat dairy products; and a prudent diet, which is characterized by a higher intake of vegetables, fruits, legumes, whole grains, fish, and poultry. The two patterns are not mutually exclusive—“You can eat at McDonald's every day and still eat a lot of fruits and vegetables,” Dr. Meyerhardt said.
Individuals in the CALGB 89803 companion study who were in the highest quintile for a Western pattern diet had nearly a four-fold increase in risk of disease recurrence or death compared with those in the lowest quintile.
Patients in the highest quintile consumed about six servings of red meat a week compared with only two for those in the lowest quintile, six servings of refined grains a day compared with two, and 2.5 sugary desserts a day compared with less than one.
“The data imply that you don't need to necessarily avoid everything in a Western pattern diet, but you do need to take it in moderation,” he said.
Interestingly, increasing intake of a prudent diet did not appear to be associated with risk of recurrence.
Meanwhile, several groups have been looking at the impact of body mass index on the risk of recurrence and death. For example, James Dignam, PhD, pooled data from 4,300 participants in various National Surgical Adjuvant Breast and Bowel Project randomized controlled trials and found that individuals who had a BMI above 35 mg/m2 or higher had a statistically significantly worse outcome than those whose BMI fell within the normal or overweight range.
Dr. Meyerhardt's group revisited the issue using data from the CALGB 89803 study data, updating individuals' BMI between the first and second questionnaires, and found similar results. Both studies showed that a BMI above 35 mg/m2 was associated with an approximately 25% increased risk of recurrence or death.
Although the increased risk may not be as large as the change in risk associated with physical activity, it is important to realize that the number of very overweight individuals in the United States has doubled over the past three decades, so a lot of individuals will be affected by the risk, Dr. Meyerhardt said.
Post diagnosis weight loss or gain, based on changes in BMI from the first to second questionnaires in participants in CALGB 89803, did not show an association with outcomes.
What to Recommend?
All of the data described are observational and thus are not absolutely conclusive. But there is no down side to a healthy diet and exercise, experts agreed. “It is probably reasonable to recommend to your patients, who are able, to engage in physical activity,” Dr. Meyerhardt concluded, noting that the association with physical exercise and outcome is the most consistent and well-studied.
As for diet recommendations, he said, “a healthy diet has implications beyond colon cancer recurrences. If you go through treatment for colon cancer it is probably a good idea to maintain a healthy diet for heart and other conditions.”