A Pan-Cancer Target Trial Emulation of Exercise and Distant Disease-Free Recurrence

We leveraged observational data to conduct a target trial emulation (TTE) framework evaluating the association of exercise on distant disease-free survival (DDFS) in a pan-cancer cohort.

To emulate a randomized controlled trial (RCT), a "historical" exercise assessment (Th) identified non-exercising (<10 metabolic equivalent of task-hours per week [MET-h/week]) patients. Repeat assessment 9-15 months later (T0) was used to classify patients into an exercise group (≥10 MET-h/week: increased exercise from Th) and a control group (up to 10 MET-h/week: minimal increase in exercise from Th). Kaplan-Meier methods and Cox proportional hazards models from the T0 assessment were used to estimate hazard ratios (HRs) for the exercise versus control group on DDFS and overall survival (OS).

A total of 3,022 patients were classified into the exercise group and 1,183 into the control group. With 5.2 years (IQR 2.7, 7.0 years) median follow-up from T0, the 5-year DDFS was 95% (95% CI, 93-96) in the exercise group and 92% (95% CI, 91-94) in the control group. Compared with the control group, the adjusted HR for the exercise group was 0.80 (95% CI, 0.59-1.09, p=0.20) for DDFS and 0.78 (95% CI, 0.55-1.11, p=0.20) for OS.

In this pan-cancer TTE, we estimated a potential 20-30% improvement in DDFS in the exercise group compared to control.

These data add to a growing body of evidence supporting further development of exercise as a therapeutic-intent strategy in primary solid tumors.