**Background:** Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic disease is the leading cause of death. Surgery for complex primary and metastatic CRC, including liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), has improved 5-year survival rates (approximately 50% for hepatic and 30% for peritoneal metastases) but is associated with high postoperative morbidity—up to 35% after liver resection and 75% after HIPEC. Multimodal prehabilitation (exercise, nutrition, psychological support, smoking cessation) has been shown to reduce complications and improve recovery in primary CRC surgery in non-academic hospitals, but its feasibility and efficacy in academic settings for complex and metastatic CRC had not been studied. This pilot study aimed to determine feasibility and potential efficacy of multimodal prehabilitation in patients undergoing complex colorectal surgery, liver resection, or HIPEC in an academic hospital.
**Methods:** This single-centre, historically controlled pilot study was conducted at Radboud university medical centre in the Netherlands from May 2019 to January 2020. All patients awaiting elective, curative surgery for complex primary CRC, liver resection, or HIPEC were considered eligible. Exclusion criteria were age <16 years, expected surgery date <3 weeks, paralysis/immobilization, ASA score ≥4, renal failure stage ≥3, and illiteracy. Sixteen patients commenced the multimodal prehabilitation program, which included: (1) a standardized exercise program with high-intensity supervised training three times per week and low-intensity training (≥60 min walking/cycling) four times per week, aiming to improve VO2peak and 1RM by ≥10%; (2) nutritional intervention with dietitian consultation, daily protein (30g whey protein), multivitamin, and vitamin D supplements; (3) psychological support for patients with HADS score >15; and (4) smoking cessation support for current smokers. All patients received perioperative care per the Enhanced Recovery After Surgery (ERAS) program. Feasibility was measured by accrual rate, completion rate, adherence (≥80% of prescribed supervised trainings), patient satisfaction, and safety. Postoperative outcomes (30-day complications per Clavien-Dindo classification, length of stay) were compared with a historical control group (March 2017–May 2019) matched 1:3 for surgical procedure type, age, ASA score, and smoking status.
**Key Results:** Of 41 patients screened, 25 were eligible; 16 commenced prehabilitation (accrual rate 64%). Reasons for non-participation included insufficient time before surgery (39%), lack of motivation, changes in treatment plan, logistical problems, and physical limitations. Fourteen patients completed the full intervention (completion rate 88%); two dropped out due to surgery being rescheduled within one week. The mean preoperative period was 26 days (range 7–46 days). Of 131 prescribed supervised training sessions, 118 (90%) were performed. The adherence rate was 69% (11/16 patients completed >80% of prescribed supervised trainings). All 16 patients underwent dietetic consultation and reported taking supplements as prescribed. One patient was referred for psychological support (one appointment). Three patients were instructed for smoking cessation; two successfully stopped preoperatively. No adverse events occurred. All patients expressed satisfaction, though some found appointments time-consuming. The complication rate was significantly lower in the prehabilitation group (37.5%, 6/16) compared to the historical control group (70.2%, 33/47; p = 0.020). Severe complications (Clavien-Dindo ≥3) occurred in 12.5% of the prehabilitation group versus 36.2% of controls, but this difference was not significant (p = 0.075). Median length of hospital stay was 6 days (prehabilitation) versus 9 days (control), also not statistically significant (p = 0.160).
**Clinical Implications:** This pilot study provides the first evidence that multimodal prehabilitation is feasible and safe in patients undergoing complex colorectal surgery, liver resection, and HIPEC in an academic setting. The accrual rate of 64% was higher than the only prior prehabilitation study in liver resection (33%). The principal barrier to participation was insufficient time between diagnosis and planned surgery (39%), suggesting that future implementation may require adjustments to surgical scheduling. The significantly lower complication rate (37.5% vs. 70.2%) and the trend toward fewer severe complications and shorter hospital stay are encouraging but must be interpreted cautiously given the small sample size, non-randomized design, and potential for selection and attention bias. The authors note that time effects in perioperative care may have influenced length of stay comparisons. Larger, adequately powered randomized controlled trials are needed to confirm these preliminary findings and determine the true benefits of prehabilitation in this high-risk surgical population.