Supervised Multimodal Prehabilitation and Clinical Outcomes in Older Patients With Frailty and Gastric Cancer

Importance: Frailty is associated with functional decline and increased postoperative morbidity. Prehabilitation may complement Enhanced Recovery After Surgery (ERAS) care to improve patient outcomes. Objective: To evaluate the effect of a multimodal prehabilitation program on functional capacity and clinical outcomes in older patients with frailty undergoing radical gastrectomy. Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in China. Participants aged 65 to 85 years with frailty (Geriatric 8 screening tool score ≤14) scheduled for elective gastrectomy or neoadjuvant chemotherapy prior to elective gastrectomy were randomized 1:1 to ERAS care either with or without prehabilitation. Recruitment for the study began in September 2022 and was completed in April 2024; data analysis was completed from September 2024 to April 2025. Interventions: The prehabilitation group (PG) underwent multimodal prehabilitation for at least 2 weeks in combination with ERAS care, while the standard ERAS group (SG) followed a well-defined ERAS pathway. Main Outcomes and Measures: The primary outcome was the proportion of patients with postoperative complications within 30 days after surgery. Secondary outcomes included functional capacity, surgical resilience, and other short-term postoperative outcomes. Results: A total of 368 participants were randomized to either the PG or SG group. In the modified intention-to-treat population of 347 participants (PG: n = 169; SG: n = 178), overall compliance with prehabilitation was 93.75%; median (IQR) participant age was 70 (68-73) years, and 95 participants (27.4%) were female. The rate of complications was lower in PG compared to SG (17.2% vs 28.7%; P = .01). In particular, significant benefits were observed in minor complications (PG: 18 of 169 patients [10.7%]; SG: 36 of 178 patients [20.2%]; P = .01) and medical complications (PG: 14 of 169 patients [8.3%]; SG: 30 of 178 patients [16.9%]; P = .02). The PG showed increased functional capacity before surgery compared to baseline (mean [SD] 6-minute walk test change, +24 [12.5] m; P < .001). Four weeks after surgery, the mean walking distance of the PG remained above baseline levels. Moreover, secondary parameters, such as chronic low-grade inflammation, preoperative physical quality of life, length of intensive care unit stay, mechanical ventilation time, and length of hospital stay, generally favored prehabilitation compared with standard ERAS care. Conclusions and Relevance: Per the results of this randomized clinical trial, a multimodal prehabilitation program may enhance physiological reserve, reduce morbidity, and promote surgical resilience in older patients with frailty undergoing radical gastrectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT05352802.