Multimodal Prehabilitation Reduces Postoperative Complications in High Risk Patients Undergoing Major Gastrointestinal Cancer Surgery

Postoperative complications leading to death represent the third leading cause of mortality worldwide, equating to roughly one in 13 deaths and forming what has been termed a hidden pandemic. Analysis of the ACS NSQIP database further illustrates this impact, revealing that 19% of surgical patients had not returned home within 30 days. The severity of these complications is strongly associated with long-term survival outcomes. However, for individuals with advanced or recurrent gastrointestinal cancers-including pelvic, peritoneal, oesophageal, hepatic, gastric, and pancreatic disease-complete surgical resection remains the sole potentially curative treatment. In Germany alone, approximately 85,000 patients undergo major gastrointestinal cancer surgery annually, making complication reduction a key clinical goal. This multicenter German trial is the first to comprehensively integrate exercise, nutrition, psychological support, and patient education into a modern multimodal prehabilitation strategy.

The main outcome measure of this trial is the incidence of severe postoperative complications defined as Clavien-Dindo grade III-V. The central hypothesis is that prehabilitation decreases postoperative complications and thus improves prognosis and survival. The intended study population includes patients with substantial comorbidities who face a high risk of complications, elevated healthcare costs, and poor cancer outcomes, often due to impaired physiological fitness and failure to complete intended oncological therapy.

Inclusion criteria are:

• age ≥18/ ≤80 years
• elective major abdominal cancer surgery (pelvic exenteration, cytoreductive surgery, oesophagectomy, transhiatal gastrectomy, hepatectomy, pancreatectomy, rectum resection)
• Duke Activity Status Index (DASI) score <40
• high risk for surgical complications:

=> presence of comorbid disease as one or more of the following:

• known or documented history of coronary artery disease
• known or documented history of heart failure or brain-derived natriuretic peptide (BNP) >400pg/mL
• high risk of pulmonary complications as documented by Ariscat score >4434
• diabetes currently treated with an oral hypoglycemic agent and/or insulin
• preoperative serum creatinine >200 μmol/l
• morbid obesity with body mass index (BMI) ≥35 kg/m2
• preoperative deconditioning as confirmed by six-minute walk test (6-MWT) <400 meters or by cardiopulmonary exercise testing (CPET) derived parameters (either anaerobic threshold (if done) <12 ml/kg/min, peak oxygen consumption (VO2) <16 mL/kg/min, peak VO2<710 mL/m2, or Ve/VCO2 [ventilator equivalents for carbon dioxide] >35)
• schedule allowing for at least 4 weeks for intervention with multimodal prehabilitation prior to surgery and patient's willingness to exercise