The whole-course of supervised home-based multi-modal prehabilitation to improve clinical outcome in patients undergoing neoadjuvant chemotherapy prior to gastrectomy: a single-center randomized controlled trial.

BACKGROUND: Although neoadjuvant chemotherapy offers survival benefits to advanced gastric cancer patients, the severe chemotherapy-related toxic side effects and the decline in physical fitness that accompany it increase the difficulty of perioperative management and may result in adverse clinical outcomes for patients undergoing surgery. METHODS: An open-label, Phase II, single-center randomized clinical trial was conducted in the Affiliated Hospital of Qingdao University. Patients with advanced gastric cancer who were planned to undergo gastrectomy after neoadjuvant chemotherapy were randomly assigned (1:1) to the study group (multi-modal prehabilitation) or the control group. The multimodal prehabilitation program, comprising exercise, nutritional support, and psychological intervention, was implemented over a duration of 10–16 weeks. The primary endpoint was the functional fitness between neoadjuvant chemotherapy and preoperative time point. The secondary endpoints were nutritional status, inflammatory factor levels, anxiety and depression condition, quality of life, the adherence to neoadjuvant chemotherapy, postoperative recovery, and 30-day morbidity. RESULTS: Between July 2024 and January 2025, 85 participants were included in the intention-to-treat (ITT) population (43 in the study group and 42 in the control group). Compared with the control group, prehabilitation had alleviated the attenuation of cardiopulmonary fitness during neoadjuvant chemotherapy (17.3 ± 21.8 m vs. − 25.8 ± 34.9 m, P < 0.001) and improved the fitness prior to surgery (29.4 ± 26.0 m vs. − 17.9 ± 33.6 m, P < 0.001). Prehabilitation resulted in higher adherence to neoadjuvant chemotherapy, better nutritional status, and superior quality of life. Patients in the study group exhibited a significantly lower incidence of postoperative pneumonia (absolute risk difference [ARD] -12.0%, 95% CI − 23.5% to − 0.5%; number needed to treat [NNT] = 9), a reduced rate of Clavien-Dindo grade II complications (ARD − 16.8%, 95% CI − 31.8% to − 1.9%; NNT = 6), as well as faster postoperative functional recovery and a shorter length of hospital stay, all of which indicated the clinical value of prehabilitation intervention. CONCLUSIONS: The whole course of supervised, home-based multi-modal prehabilitation improves functional capacity prior to gastrectomy, which attenuates the adverse reaction of neoadjuvant chemotherapy. Improved physical, psychological, and nutritional status preoperatively may translate to better postoperative outcomes. TRIAL REGISTRATION: NCT06521541 ( http://www.clinicaltrials.gov ).