Tailored Nutrition vs. Exercise Prehabilitation Before Colorectal Cancer Surgery

Hypothesis: Tailored preoperative nutritional therapy in a regular clinical setting improves postoperative functional capacity, and while nutritional intervention alone may improve surgical outcome, multimodal prehabilitation combining nutrition and exercise provides additional benefit, particularly improvement in physical function. Design: This is a three-armed, open-label, multicentre, parallel-group randomized controlled superiority trial comparing standard of care, tailored nutritional intervention alone, and multimodal prehabilitation (nutrition plus structured exercise) in patients undergoing elective colorectal cancer surgery. Participants are allocated 1:1:1 using a computer-generated randomization sequence with randomly permuted block sizes, stratified by study site, nutritional risk (NRS-2002) and clinical frailty score. Data are collected at three time points: baseline (first surgical consultation), after completion of the preoperative intervention (preferably the day before surgery), and approximately 30 days after surgery. Interventions: The nutrition intervention consists of individualised dietary counselling from a clinical dietitian, targeting a protein intake of 1.2-1.5 g/kg/day, supplemented as needed with oral nutritional supplements. The multimodal prehabilitation intervention adds a structured, physiotherapist-guided home exercise programme (aerobic and resistance training, 3 times weekly) to the nutrition intervention. The intervention period reflects the normal clinical waiting time to surgery, limited to a minimum of 2 and a maximum of 5 weeks. Sample size: Based on pilot data and power calculations from the dHOPE study in the same patient population, using a standard deviation for change in 6-minute walk test of 43 metres, alpha=0.05 and 80% power, 40 evaluable patients per group are needed. Allowing for an estimated 15% combined screen failure and dropout, a total of 140 patients will be enrolled. Statistics: Analyses will follow the intention-to-treat principle. The primary endpoint will be analysed using a linear mixed-effects model including treatment group, time and the group-by-time interaction, adjusted for baseline 6-minute walk test and the stratification variables. Continuous secondary outcomes will be analysed with similar mixed models; binary outcomes with logistic regression. Retrospective substudy: A separate substudy will assess body composition and nutritional status retrospectively, based on routinely acquired preoperative abdominal CT scans and available clinical data, in order to calculate whether participants meet the Global Leadership Initiative on Malnutrition (GLIM) criteria for malnutrition and to explore associations between body composition, nutritional status, functional reserve, and postoperative outcomes. No additional CT scans are performed for study purposes, and results do not influence clinical treatment during the study.