Men who were physically active after the diagnosis of non-metastatic colorectal cancer experienced a significantly decreased risk of colorectal cancer-specific death as well as death from any cause. Men who engaged in at least 27 MET-hours per week had > 50% lower risk of colorectal cancer-specific mortality compared to relatively inactive men. This association was consistently detected, regardless of age, stage, body mass index, year of diagnosis, location of tumor and pre-diagnosis physical activity.
These findings are consistent with 2 prior reports of physical activity after diagnosis in prospectively observed colorectal cancer survivors.5, 6
In a cohort of 573 women with colorectal cancer, the most active women had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.39 (95% CI, 0.18 to 0.82), compared to inactive women.5
Similarly, in a cohort of 832 men and women with stage III colon cancer who received adjuvant therapy on a National Cancer Institute-sponsored clinical trial, the adjusted hazard ratio for disease-free survival amongst those was 0.55 (95% CI, 0.33 to 0.91).5
Thus, the adjusted hazard of 0.47 detected in this cohort of men is consistent with those studies. Further, the spline curves in this study and from the study utilizing the clinical trial cohort5
both suggest a measurable risk reduction between 6–12 MET-hours per week, with a potential threshold between 30–35 MET-hours per week. A notable difference in this cohort is that 51% of colorectal cancer survivors in this current cohort engaged in at least 18 MET-hours/week, compared to 26% of survivors in the Nurse’s Health Study and 28% of survivors in the NCI-sponsored trial.5, 6
The mechanism for this consistent association between physical activity and colorectal cancer-specific survival is unknown, however hyperinsulinemia is a potential etiology.14–16
Insulin and the insulin-like growth factor (IGF) family have been associated with enhanced tumor growth and anti-apoptosis 16
and colorectal cancer risk is elevated in individuals with higher circulating levels of insulin or C-peptide (a marker of insulin secretion) and IGF-1.17–22
Patients who develop recurrence of colorectal cancer have micrometastases at diagnosis. An environment that allows such microscopic tumors to proliferate could be detrimental. Physical activity may lower tissue insulin and IGF levels and raise beneficial IGF binding proteins to influence exposure of these growth factors on micrometastases. Other mechanisms proposed in the association between exercise and colon cancer development may also be relevant towards the progression of established cancer, including immune modulation and anti-inflammatory actions.23–25
Advantages of this cohort derived from the Health Professionals Follow-up Study are the prospective collection of exposures, the diligent medical record review of self-reported colorectal cancer and deaths and the sample size. Nonetheless, there are limitations that are worth noting. Beyond cause of mortality, data on cancer recurrences were not available in this cohort. Nonetheless, as median survival for metastatic colorectal cancer was approximately 10 to 12 months during much of the time period of this study,26
colorectal cancer-specific mortality should be a reasonable surrogate for cancer-specific outcomes. Treatment data are not collected in this cohort. However, nearly 60% of patients had stage I or II disease, in which surgery alone would generally be standard of care and no interaction by stage was observed. Further, although there are differences in the likelihood of use of adjuvant chemotherapy based on factors such as socioeconomic class, the fairly homogenous nature of this cohort (professional male health care providers) would likely increase the probability of at least standard therapy.27, 28
Co-morbidities and access to healthcare may also confound these findings. Given the population studied, we would expect the latter to be relatively diminished. Though co-morbidities have been shown to affect mortality in colorectal cancer survivors,29–31
such diseases are less likely to affect disease recurrence and thereby colorectal-cancer specific mortality. Finally, our data are limited to leisure-time exercise; occupational physical activity is not surveyed in our questionnaires.
As in prior analyses5, 6
, we considered the possibility that sick patients (with cancer recurrences and limited survival) will exercise less. To minimize the bias by occult cancer recurrence, we excluded recurrences or deaths within six months of the activity assessment in the primary analysis and continued to observe a positive impact of exercise when extending this restriction to 12 months. Finally, we would expect few patients to have undetected recurrences over extended periods of time, given the relatively brief natural history of recurrent colon cancer.
Patients who underwent treatment for colorectal cancer may be considered limited in their ability to exercise. However, Arndt and colleagues reported that one year after surgery of the primary tumor, patients with colorectal cancer reported their physical functioning and global quality of life nearly identical to those of a non-cancer population.32
These results provide further support that physical activity after a colorectal cancer diagnosis may lower the risk of death from that disease. A randomized study for high risk stage II and stage III colon cancer survivors that will compare general education materials to a program with supervised physical activity sessions and behavioral support delivered over 3 years will soon open; the primary endpoint is disease-free survival.33
The findings from this study further support that effort.