Simple Summary Gastrointestinal cancers comprise over 25% of new cancer cases. Surgery is the primary curative treatment. Prehabilitation before surgery aims to optimize the patient's global condition to improve postoperative recovery. These programs usually include nutritional, physical activity, and/or psychological interventions. However, the benefits remain unclear. This review summarizes the latest evidence of preoperative prehabilitation on postoperative outcomes after gastrointestinal cancer surgery and discusses new potential therapeutic targets. Preoperative interventions, combining at least nutrition and physical activity, appear to improve physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. Further studies are needed to confirm our findings, identify surgical cancer patients more likely to benefit from prehabilitation, harmonize interventions and integrate new therapeutic strategies. The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.
