Exercise Increases Survival After Colon Cancer Diagnosis

BOSTON, July 17 -- Regular exercise more than doubles the length of disease-free survival in patients treated for advanced colon cancer, according to researchers here.

In addition, patients who continue exercising regularly or start being active after a diagnosis of colorectal cancer can improve rates of cancer-specific and overall mortality, wrote Jeffrey A. Meyerhardt, M.D., of the Dana Farber Cancer Institute here, and colleagues in other centers, in the online and Aug. 1 editions of the Journal of Clinical Oncology.

The findings, reported in two separate studies, confirm that physical activity is associated with reduced or delayed recurrence of colorectal cancer even in patients treated for stage III metastatic disease.

Similar protective effects of moderate exercise have been associated with disease-free survival following breast cancer diagnosis in women and prostate cancer diagnosis in men have been reported by other researchers.

"From previous studies we know that regular physical activity reduces the risk of developing colon cancer, but until now few studies have looked at the survival effect of exercise on people who have been treated for disease," said Dr. Meyerhardt, the principal investigator for both studies. "While our work found a significant benefit for patients who exercise, it's important that exercise be seen as a supplement to, not a replacement for, standard therapies."

In the first study, investigators from the Cancer and Leukemia Group B (CALGB) conducted a prospective observational study of 832 patients with stage III colon cancer who were enrolled in a randomized adjuvant chemotherapy trial.

Patients were eligible for the exercise study if they had undergone a complete surgical resection of the primary tumor within 56 days of study entry and had regional lymph node metastases (stage III colon cancer) but no evidence of distant metastases.

Six months after completion of therapy, the patients were asked to report on their average hours spent per week over the past two months in various forms of exercise, as well as daily physical activities such as flights of stairs climbed and usual their usual walking pace. Patients who had disease recurrence or died within 90 days of their physical activity assessment (and presumably might be less active) were excluded to minimize the possibility of bias by occult recurrence.

The investigators found that the most active patients-those with more than 27 metabolic equivalent task-hours per week-had significantly greater disease-free survival (cancer recurrence or death from any cause) compared with the least active patients (those with less than three metabolic equivalent task-hours per week).

The adjusted hazard ratio for disease-free survival for the most active patients compared to the least active was 0.55 (95% confidence interval, 0.33 to 0.91), and for patients who reported having 18 to 26.9 metabolic equivalent task-hours per week, the adjusted hazard ratio was 0.51 (95% CI, 0.26 to 0.97; adjusted P for trend = 0.01).

The benefits of exercise held up even when the numbers of involved lymph nodes and patient performance status at baseline were taken into account, the authors noted.

"The benefit associated with physical activity was not significantly modified by sex, body mass index, number of positive lymph nodes, age, baseline performance status, or chemotherapy received. Moreover, the benefit remained unchanged even after excluding participants who developed cancer recurrence or died within 6 months of activity assessment," the authors reported.

The second study was a prospective observational look at 573 women with stage I to III local and regional, non-metastatic colorectal cancer who were enrolled in the longitudinal Nurses' Health Study.

The investigators looked at cancer-specific mortality and overall mortality according to predefined physical activity categories both before and after diagnosis. They also looked at the question of whether increased activity after a diagnosis could have a beneficial effect.

As in the CALGB study, the authors excluded women who died within six months of their postdiagnosis physical activity assessment.

They found that after diagnosis of nonmetastatic colorectal cancer, increasing levels of activity reduced both significantly reduce cancer-specific mortality and overall mortality (P for trend =0.008 and 0.003, respectively).

The adjusted hazard ratio for colorectal cancer-specific mortality for women who reported 18 or more metabolic equivalent task-hours per week was 0.39 (95% CI, 0.18 to 0.82) compared with women who reported less than three metabolic equivalent task-hours weekly.

The adjusted hazard ratio for overall mortality for the more active women compared with the least active was 0.43 (95% CI, 0.25 to 0.74).

The results remained the same even after they excluded from the analysis women who died within one or two years of the activity assessment.

The investigators also found that women who upped their activity levels only after a diagnosis of colorectal cancer also enjoyed a significant survival benefit. Compared with women who made no changes in their exercise routine after diagnosis, the hazard ratio for colorectal-cancer death was 0.48 (95% CI, 0.24 to 0.97), and for all-cause mortality the hazard ratio was 0.51 (95% CI, 0.30 to 0.85).

"As clinicians, researchers, and policy makers, we have long awaited such confirmatory findings," wrote Wendy Demark-Wahnefried, Ph.D., of the School of Nursing and department of surgery at Duke in Durham, N.C., in an accompanying editorial.

"Our exercise interventions, as well as the current guidelines for cancer survivors, and what we ultimately tell our patients, is that exercise may be beneficial, with guidance based largely on proven associations that exist between physical activity and specific comorbid conditions (such as heart disease or osteoporosis) to which cancer survivors are especially prone, or associations between physical activity and other factors, such as quality of life, functional decline, and fatigue," Dr. Denmark-Wahnfried wrote.

In discussing the need for corroboration by a randomized, controlled prospective trial, she pointed out potential difficulties and solutions with funding such a study. "There is no doubt that the pharmaceutical industry would back an agent with potential to reduce cancer recurrence by at least 50%, but who will back a trial that evaluates the potential benefit of sneakers and sweatpants?" she asked. "Would Nike 'Just do it'? Perhaps, and indeed, it would be a magnificent gesture of goodwill."