Clinical Effectiveness and Safety of Multimodal Prehabilitation in Colorectal Cancer Surgery—A Narrative State-of-the-Art Review of Research and Clinical Trials

Background/Objectives: Colorectal cancer (CRC) remains one of the most common malignancies worldwide. Despite advances in surgical techniques and the implementation of Enhanced Recovery After Surgery (ERAS) protocols, a substantial proportion of patients continue to experience postoperative complications and persistent functional impairment. Multimodal prehabilitation, combining physical exercise, nutritional optimization, and behavioral support, has been proposed as a strategy to enhance functional reserve prior to surgical treatment. The aim of this review was to provide a critical narrative evaluation of current clinical evidence regarding the effectiveness and safety of prehabilitation in patients with CRC. Methods: A targeted literature review was conducted in PubMed, Embase, CINAHL, Scopus, and Web of Science (2015–2025), identifying 23 primary studies, including 18 randomized and 5 non-randomized trials. Results: Most multimodal prehabilitation programs resulted in significant improvements in functional capacity prior to CRC resection. Functional outcomes were most commonly assessed using the six-minute walk test, cardiopulmonary fitness parameters, and measures of muscle strength, with good tolerance and high patient adherence. Several studies also demonstrated reductions in postoperative complication rates, shorter hospital stays, and faster recovery of independence, particularly among older patients, those with frailty, or reduced baseline functional capacity, although these effects were not fully consistent across studies. Conclusions: Available clinical evidence supports multimodal prehabilitation as a safe and feasible strategy that consistently preserves and enhances functional reserve prior to CRC surgery. However, its capacity to modify hard perioperative outcomes (such as complication rates and length of stay) remains inconsistent across current RCTs, showing clear efficacy predominantly in targeted high-risk, frail, or malnourished cohorts.