Resistance vs Aerobic Prehabilitation Before Colorectal Cancer Surgery

Background: Prehabilitation, i.e. preparing patients physically, nutritionally and mentally in the weeks before surgery, consistently improves preoperative functional capacity, but its effect on postoperative morbidity after colorectal surgery remains uncertain, especially when compared with Enhanced Recovery After Surgery (ERAS) care. Possible reasons include the lack of a standardized exercise protocol, the unknown optimal type of training, the unidentified patient subgroup most likely to benefit, and heterogeneous patient compliance in largely unsupervised, outpatient programs. In our preclinical study in a rat model, resistance training was associated with better colonic anastomosis healing than aerobic training; no human comparative trial has addressed this question. Objectives: (1) To compare the effect of resistance training, aerobic endurance training and their combination, delivered within a trimodal prehabilitation program, on postoperative morbidity after elective colorectal resection; (2) to identify, by subgroup analysis, patients most likely to benefit from physical prehabilitation; (3) to assess factors influencing patient compliance and the association between compliance and outcomes. Design: Single-center, prospective, randomized, controlled, parallel-group trial with four arms (1:1:1:1). Allocation is performed automatically by software randomization embedded in REDCap at enrollment and cannot be modified. Personnel recording outcome data are blinded to group allocation. The trial follows CONSORT recommendations. Standard care in all arms: dietitian-led nutritional prehabilitation with oral nutritional supplements when indicated; screening for anxiety and depression (BDI, PHQ-9, STAI) with clinical psychologist consultation for high-risk patients; breathing exercises and incentive spirometry training; nurse-led ERAS education, stoma education when indicated, and counseling on smoking and alcohol cessation. Perioperative care follows an audited ERAS program with \>80% protocol compliance. Assessments: baseline nutritional (MUST, InBody), physical (6-minute walk test, 1-minute sit-to-stand test, handgrip strength, frailty scores: CFS, mFI-5, FRAIL), psychological and quality-of-life (SF-36, GIQLI) assessment; CT-based body composition (L3 skeletal muscle index, myosteatosis). Compliance is monitored through a patient diary, weekly physiotherapy visits or phone calls, and daily pulse-wave recordings. Assessments are repeated on the day before surgery and 8 weeks after surgery. Complications are recorded according to the Clavien-Dindo classification. Long-term oncological outcomes are followed up within a separate institutional registry study. Statistics: Sample size of 120 patients per arm (480 total) was calculated for an expected reduction in postoperative morbidity from 30% to 15% (alpha 0.05, power 80%). An interim analysis is planned after 30 patients per arm to assess the ethical continuation of the trial. Each experimental arm will be compared with the control arm, followed by pairwise comparisons between experimental arms with adjustment for multiple comparisons. Classification and Regression Tree (CART) analysis will be used to identify the subgroup most likely to benefit from prehabilitation.