Multimodal prehabilitation in colorectal cancer surgery: randomized clinical trial
Felix Bjerregaard, Klas Pekkari, Daniel Asklid, Claes Anderin, Karin Westberg, Richard Marsk, Ulf O GustafssonAbstract
Background
Colorectal cancer (CRC) surgery remains associated with substantial postoperative morbidity despite implementation of enhanced recovery after surgery (ERAS). Prehabilitation improves surgical outcomes, but evidence remains inconsistent. This study evaluated whether multidisciplinary prehabilitation reduces postoperative complications and whether treatment effects vary according to baseline physical function.
Methods
This single-centre randomized clinical trial was conducted at a tertiary referral hospital in Stockholm, Sweden (28 October 2021–23 April 2025). Adults with histologically confirmed CRC scheduled for elective resection were randomized 1 : 1 to multidisciplinary prehabilitation (medication review, nutritional counselling, supervised exercise, and targeted risk optimization) or standard care (ERAS). Analyses followed a modified intention-to-treat (mITT) principle. Prehabilitation was initiated within 3 days of enrolment. The primary outcome of interest was postoperative complications (Clavien–Dindo grade ≥ I). Secondary outcomes included severe complications (Comprehensive Complication Index), reoperations, length of hospital stay (LOS), postoperative weight loss, physical performance and function (6-minute walk test, Timed Up and Go test, and 30-second chair stand test), health-related quality of life (EORTC QLQ-C30), mental health (Hospital Anxiety and Depression Scale), and correlation with the Disability Rating Index (DRI) score.
Results
Among 328 randomized patients, 242 underwent CRC surgery and were included in the mITT analysis (120 control, 122 intervention). Postoperative complications occurred in 46.2% of patients, with no significant difference between the intervention and control groups (47.5% versus 45.0%, respectively). Severe complications occurred in 19.0% of patients and were numerically less frequent in the intervention group, but the difference was not statistically significant. LOS and reoperation rates were similar. The intervention group had lower postoperative weight loss and modest improvements in physical performance and patient-reported physical function at 30 days. In exploratory analyses, a significant interaction was observed between treatment allocation and baseline DRI score, indicating greater reduction in severe complications among patients with higher levels of preoperative disability (P = 0.011).
Conclusions
Multidisciplinary prehabilitation did not reduce postoperative complications after CRC surgery. However, exploratory analyses suggest that patients with greater preoperative disability derive greater benefit, supporting targeted prehabilitation strategies in higher-risk populations. Registration number: NCT04909567 (https://clinicaltrials.gov/).