Endometrial cancer is the sixth most diagnosed cancer in women worldwide, and unlike with most cancers, mortality rates have increased in recent decades. An increase in the prevalence of obesity and diabetes, known risk factors for endometrial cancer, may be contributing to higher death rates in this population, as many survivors of endometrial cancer are also living with obesity-related diseases, such as cardiovascular disease. Physical activity (PA) is a well-studied intervention for managing obesity and diabetes. Although evidence suggests that it can also improve survival outcomes in breast and colorectal cancers, the role of PA in endometrial cancer survival remains unclear.

For a paper published in the Journal of Clinical Oncology, we and our colleagues conducted a prospective cohort study to determine if PA is associated with disease-free or overall survival among survivors of endometrial cancer. Specifically, we examined the strength of associations by the timing (pre- versus post-diagnosis), domain (total, recreational, household, occupational), and dose (frequency, intensity, duration as assessed by MET-hours/week/year) of activity.

Participants were 425 women in Alberta, Canada with invasive endometrial cancer diagnosed between 2002 and 2006 and followed for all outcomes to 2019. At baseline, they were, on average, 58 years old with a mean BMI of 31 kg/m2, and 81% had stage I endometrial cancer. Pre- and post-diagnosis PA levels were measured by the interviewer-administered Lifetime Total Physical Activity Questionnaire at approximately 4 months and 3 years after diagnosis, respectively. After a median follow-up of 14.5 years, associations between PA and survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, BMI, menopausal status, hormone therapy use, family history of cancer, and comorbidities.


Higher Pre- & Post-Diagnosis Recreational Physical Activity may Improve Survival Outcomes

We observed no dose-response relationship between pre-diagnosis total PA and disease-free or overall survival. However, when examining results by the domain of PA, the highest versus lowest tertiles of pre-diagnosis recreational PA improved disease-free survival by 46%.

For women who engaged in the highest versus lowest tertiles of post-diagnosis activity, total PA was associated with a 64% improvement in disease-free survival, while recreational post-diagnosis PA was associated with a 67% improvement in both overall and disease-free survival.


Physical Activity Is a Priority Across the Lifespan

Regarding patterns of change from pre- to post-diagnosis levels of PA, we found that women with higher levels of PA (>10 MET-hours/week/year) before and after diagnosis experienced a 65% and 57% improvement in disease-free and overall survival, respectively, compared with women who had lower levels of PA (<10 MET-hours/week/year) before and after diagnosis (Table).

Given that the greatest survival benefits were experienced by women who sustained high levels of recreational PA from pre- to post-diagnosis, there is a need for oncologists and other clinicians to promote PA throughout the lifespan as a modifiable risk factor to reduce mortality from endometrial cancer.


Physical Activity may Improve Survival Outcomes Independently of BMI

Many hypothesized biological pathways suggest that PA primarily reduces the risk of cancer mortality through an impact on obesity, specifically reductions in adiposity, inflammation, adipokines, insulin resistance, and endogenous sex hormones.

Analyses stratified by BMI generated similar results for participants with a higher (≥30 kg/m2) versus lower BMI (<30 kg/m2) at baseline, suggesting that PA may improve survival outcomes independently of BMI.


Survival Benefits Offered by Recreational PA Are Achievable for Endometrial Cancer Survivors

We observed survival benefits with 5-13 MET-hours/week/year of recreational activity (equivalent to 100-300 minutes/week of moderate-intensity activity), a level achievable by most populations. Currently, less than one-half of cancer survivors are physically active. After providing a diagnosis of endometrial cancer, oncologists should encourage patients who are physically active to maintain their habits and empower patients who are inactive to incorporate more recreational PA into their lives.

Observational studies are needed that objectively measure PA and health-related fitness to improve understanding of the association between PA and endometrial cancer survival outcomes.

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