Charles S. Fuchs, MD, MPH
Erin Van Blarigan, ScD
Following guidelines for proper nutrition, maintaining a healthy weight, and staying physically active may improve survival among patients treated for colon cancer, according to the results of a study with nearly 1,000 patients followed for a median of 7 years.1 “The study suggests that if patients take a relatively healthy approach to lifestyle, they may significantly reduce the likelihood of cancer mortality,” study coauthor Charles S. Fuchs, MD, MPH, said in an interview with The ASCO Post. Dr. Fuchs is Director of the Yale Cancer Center and Physician-in-Chief of Smilow Cancer Hospital, New Haven, Connecticut. The lead author of the study was Erin Van Blarigan, ScD, Assistant Professor of Epidemiology and Biostatistics at the University of California, San Francisco.
The 992 patients in the study were diagnosed with stage III colon cancer and had received adjuvant chemotherapy within 8 weeks of resection. Midway through and 6 months after chemotherapy, the patients completed lifestyle surveys, administered in the clinic. Patients were evaluated regularly for cancer recurrence, mortality, and other health events during the study period. “Patients were regularly monitored by their physician, and at two time points in the first 18 months of the study, we conducted a detailed assessment of their diet, lifestyle, and supplement use,” Dr. Fuchs said.
Survey responses were used to determine how closely the patients had adhered to American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors.2 These guidelines include eating a diet rich in vegetables, fruits, and whole grains; maintaining a healthy body weight; and staying physically active. Previously reported studies have looked at the impact of individual diet and lifestyle factors on colorectal cancer outcomes, but the authors of the current study believe this is the first study to look at the combined effect of body mass index (BMI), physical activity, and diet after colorectal cancer diagnosis.
Reduced Risk of Death at 5 Years
Based on BMI; physical activity; and intake of vegetables, fruits, whole grains, and red/processed meats, each patient was assigned an American Cancer Society (ACS) guideline score from 0 to 6, with a higher score indicating healthier behaviors. Compared with patients with a 0 to 1 ACS guideline score, those with a score between 5 and 6 “had a 42% lower risk of death during the study period,” the researchers reported. The 5-year survival probability was 85% for patients with high scores vs 76% for those with low scores—“a 9% absolute reduction in the risk of death at 5 years.”
The research findings may “span all stages of colon cancer,” Dr. Fuchs said, but all study patients had stage III lymph node–positive colon cancer. “Let’s be clear: This study was specifically in patients with stage III disease.”
‘Cancer Control Gem’
Study participants had enrolled between 1999 and 2001 in CALGB 89803, which tested adding irinotecan to fluorouracil and leucovorin, the standard of care at the time. Noting that CALGB 89803 was a negative study, and “the investigational arm was far more toxic than standard care,” an accompanying editorial declared that this latest study “represents a cancer control gem that came out of the ashes of this trial.3”
The editorial went on to advise clinicians: “If you were skeptical about emphasizing nutrition and physical activity for colorectal cancer survivors based on the nature of the endpoints previously examined or the size of demonstrated effects, or the fact that most of the similar studies were conducted among patients with breast cancer, these data should soften those concerns. If you previously gave vague recommendations about diet and exercise, now you can be more precise and recommend 5 to 6 servings per day of fruits and vegetables and 150 minutes per week of exercise.”
Improvement in Disease-Free Survival
In addition to improved overall survival, the study found “a statistically significant trend toward improved disease-free survival” and a “nonstatistically significant trend for improved recurrence-free survival” for patients with the highest vs the lowest ACS guideline score. “From a purely scientific standpoint, these are critical endpoints. Furthermore, the healthy lifestyle may improve overall survival as a result of reducing the risk of other diseases, such as heart disease, which is a good thing,” Dr. Fuchs noted. “But if you are also trying to understand scientifically whether it modified the natural history of cancer, you want to look at both disease-free and recurrence-free survival,” he added.
The study suggests that if you take a relatively healthy approach to lifestyle, you can significantly reduce the likelihood of cancer mortality.— Charles S. Fuchs, MD, MPH
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Patients, however, are more focused on overall survival and so often ask, “‘What are the odds my cancer will come back?’ because that is the proximate issue,” Dr. Fuchs said. So after curative surgery, the tangible concern is recurrence-free survival. It is disease-free survival. “It does come up in the conversation, but not in the same scientific way that we as investigators need to focus on to understand the biology.”
Closer Look at BMI
“The ACS guidelines recommend a BMI of 18.5 to 24.9 kg/m2. However, a BMI of 23.0 to 29.9 kg/m2 has been associated with a lower risk of recurrence or death among patients with colorectal cancer,” the researchers wrote, citing a meta-analysis that included 58,917 patients followed for a median of 9.9 years.4 In the current study, researchers examined alternative cut-points for BMI and assigned 2 points for a BMI of 23.0 to 29.9 kg/m2, 1 point for a BMI of 18.5 to 22.9 kg/m2, and 0 points for a BMI of 35 kg/m2 or higher.
“When you get below a BMI of 21 kg/m2, the data become very confounded,” Dr. Fuchs noted, “particularly in the cancer populations. There are people who are healthy who have a BMI between 18 and 21 kg/m2; then there are people who are between 18 to 21 kg/m2 because they are ill, and it actually is a manifestation of their illness.”
Unclear About Red Meat
“Contrary to the guidelines, low intake of red and processed meat after colon cancer was associated with an increased risk of death,” according to the study report. “Higher protein may be beneficial to cancer survivors,” and “it is possible that red meat is inversely associated with colon cancer mortality, despite being associated with colon cancer incidence.”
“There is no question that red meat in moderate to heavy consumption can increase one’s risk of colon cancer. That is now an accepted standard for risk,” Dr. Fuchs stated. But currently, “it is not clear,” he said, whether red meat intake negatively influences outcomes among cancer survivors. As noted in the study report, “Further research is needed to inform guidelines regarding meat intake for patients with cancer.”
Alcohol Use Controversial
Although alcohol use is not included in the ACS guidelines for cancer survivors, researchers conducted a secondary analysis including alcohol intake in the score due to “patient interest and a possible benefit of low to moderate consumption for colon cancer survivors.” Results showed that compared with abstainers, patients consuming low to moderate amounts of alcohol had a nonstatistically significant decreased risk of death (hazard ratio [HR], 0.87), and heavy drinkers had a nonstatistically significant increased risk of death (HR, 1.28).
“This is a controversial area,” Dr. Fuchs commented. “When you look at risk factors for heart disease and risk factors for cancer, they largely go in the same direction—eating right can accomplish both. Exercising can help both. When it comes to alcohol, light to moderate drinking, at least in most studies, reduces your risk of heart disease, but it does not reduce your risk of cancer, and heavier drinking increases your risk of cancer,” he said.
“I don’t think there is any question that if you look at all-cause mortality, and I am an author of one of these studies, it is pretty clear that light to moderate drinking is associated with a lower all-cause mortality, principally through reduction of heart disease, because that is a dominant risk of mortality among Americans,” Dr. Fuchs stressed.
“As physicians, we need to inquire about people’s alcohol consumption, because sadly, every once in a while, you will find someone is actually consuming significant amounts, and then there is no health benefit. Even for heart disease, the benefit is only for light to moderate alcohol consumption. Heavy drinkers have higher mortality.” ■
DISCLOSURE: Dr. Fuchs reported consulting or advisory roles with Lilly, Sanofi, Bayer, Merck, Entrinsic Health Solutions, Five Prime Therapeutics, Agios, CytomX, Gilead Sciences, Taiho Pharmaceutical, and Genentech/Roche. Dr. Van Blarigan reported no conflicts of interest.
REFERENCES
1. Van Blarigan EL, Fuchs CS, Niedzwiecki D, et al: Association of survival with adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors after colon cancer diagnosis: The CALGB 89803/Alliance Trial. JAMA Oncol. April 12, 2018 (early release online).
2. Rock CL, Doyle C, Demark-Wahnefried W, et al: Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62:243-274, 2012.
3. Fisch MJ, McNeill LH, Basen-Engquist KM: Helping colorectal cancer survivors benefit from changing lifestyle behaviors: Implementation science and private industry collaboration to the rescue. Editorial. JAMA Oncol. April 12, 2018 (early release online).
4. Lee J, Meyerhardt JA, Giovannucci E, et al: Association between body mass index and prognosis of colorectal cancer: A meta-analysis of prospective cohort studies. PLoS One 10:e0120706, 2015.
