Multimodal Prehabilitation In Pancreatic cancer Patients undergoing surgery (PIPS): study protocol for a randomized controlled trial.

BACKGROUND

Pancreatic cancer surgery is challenging and associated with up to a 70% complication rate, which translates to poor postoperative recovery and patient health-related quality of life (HRQoL). Previous studies showed that preoperative low functional capacity and malnutrition have been associated with inferior postoperative outcomes. Considering the high frequency of older and frail patients, often deconditioned by long-course neoadjuvant chemotherapy, the preoperative period, including the time window after chemotherapy, is a unique opportunity to condition modifiable risk factors (e.g., functional capacity, nutritional status). This manuscript outlines the protocol for a randomized controlled trial investigating the impact of a multimodal prehabilitation program on postoperative complications and recovery following pancreatectomy.

METHODS

This is a single-center, randomized controlled trial evaluating a 4-6-week multimodal prehabilitation program (physical, nutritional, and psychological interventions) compared with usual perioperative care in adults scheduled for pancreatic surgery, whether upfront or following chemotherapy for pancreatic or periampullary cancer. The primary outcome will be the severity of postoperative complications, measured using the Comprehensive Complication Index (CCI®). Secondary outcomes include the level of functional capacity, time to functional recovery, length of stay, body composition parameters, and generic and disease-specific health-related quality of life (HRQoL). Follow-up assessment will be conducted at 30, 60, 90, 180, and 365 days post-surgery. A sample size of 238 patients is estimated to provide adequate power to detect a clinically meaningful difference in CCI® between groups.

DISCUSSION: A multimodal prehabilitation program may enhance functional capacity, improve nutritional status, and increase skeletal muscle mass, thereby promoting a shift from a catabolic to an anabolic state. By modulating systemic inflammation and supporting cardiovascular and immune function, this strategy could lead to fewer postoperative complications, a shorter length of stay, and a faster recovery of health-related quality of life. Positive findings from this trial would carry strong clinical significance and could be practice-changing, potentially informing future guidelines for the implementation of multimodal prehabilitation in patients undergoing pancreatic cancer surgery.

TRIAL REGISTRATION: Trial Registry NCT06069297. Registered on August 25, 2023.