Pancreatic Enzyme Replacement Therapy (PERT) in Pancreatic Cancer: First U.S. Consensus Highlights on Dosing, Management, and Provider Inertia

Abstract PURPOSE Exocrine pancreatic insufficiency (EPI) is a highly prevalent, yet modifiable determinant of treatment tolerance in pancreatic cancer (PC). Despite its clinical significance, management remains inconsistent due to a lack of oncology-specific guidelines. This project aimed to establish the first U.S. multidisciplinary consensus to standardize pancreatic enzyme replacement therapy (PERT) dosing, education, and longitudinal management in pancreatic oncology. METHODS A mixed-methods design was employed, integrating a parallel literature review, six virtual focus groups with patients and clinicians (n = 28), and a formal modified Delphi process. A multidisciplinary panel of 17 experts, including medical, surgical, and radiation oncologists, advanced practice providers, and oncology dietitians, independently rated and refined draft statements over two iterative rounds. Consensus was defined a priori as ≥ 70% agreement. RESULTS The process yielded 15 final Consensus Statements, all achieving ≥ 81% agreement. This manuscript highlights a critical subset of six statements focusing on clinical application (CS 10–15), which achieved 94%–100% consensus. Recommendations define standardized starting doses (48,000–72,000 lipase units per meal), evidence-based titration protocols, multi-level patient education requirements, and strategies to mitigate financial toxicity and pill burden. CONCLUSION These consensus statements provide a practical, evidence-based framework to reduce provider inertia and practice variability. Broad implementation of these standards offers a vital opportunity to stabilize nutritional status, improve quality of life, and optimize treatment continuity for patients with PC.