Feasibility, Safety, and Preliminary Efficacy of Exercise During and After Neoadjuvant Rectal Cancer Treatment: A Phase II Randomized Controlled Trial

•Exercise during and after chemoradiation for rectal cancer was feasible.•Exercise did not improve fitness, treatment toxicities, or treatment completion.•Exercise significantly improved pathologic complete response to chemoradiation.•Study limitations include small sample size and limited follow-up.•Larger phase II and III trials in this clinical setting are warranted. Neoadjuvant chemoradiation (NACRT) improves outcomes for patients with rectal cancer; however, there are dose-limiting toxicities and only a 15% to 27% pathologic complete response (pCR) rate. Exercise may help manage toxicities and improve treatment response, but feasibility and early efficacy have not been established. EXERT was a phase II trial designed to establish the feasibility and safety of exercise and provide the first evidence of efficacy. Patients with rectal cancer scheduled to receive NACRT were randomly assigned to usual care (n = 18) or exercise (n = 18) involving supervised exercise during NACRT and unsupervised exercise after NACRT. The primary outcome was cardiorespiratory fitness (VO2 peak). Clinical outcomes included treatment toxicities, treatment completion, and treatment response. Median attendance at supervised exercise sessions during NACRT was 82%, and median self-reported exercise after NACRT was 90 min/wk. From baseline to post-NACRT, VO2 peak increased by 0.4 mL·kg−1·min−1 in the exercise group and decreased by 0.8 mL·kg−1·min−1 in the usual care group (P = .47). There were no significant differences between groups for grade 3/4 toxicities or treatment completion. Of 18 patients in the exercise group, 10 (56%) achieved pCR/near pCR compared with 3 of 17 (18%) in the usual care group (P = .020). Exercise during and after NACRT is feasible for many patients with rectal cancer and may improve pCR despite limited fitness improvements. Larger trials are warranted to confirm if exercise is an effective intervention for improving treatment outcomes in this clinical setting. Exercise has potential to improve outcomes for patients with rectal cancer receiving neoadjuvant chemoradiation; however, there is scant research. This study sought to determine the feasibility of exercise and provide the first evidence of efficacy. Our study showed that exercise is feasible for many patients with rectal cancer and may improve the efficacy of chemoradiation despite limited improvements in fitness.