Early Versus Delayed Pancreatic Enzyme Replacement Therapy After Pancreatic Cancer Surgery

Objectives: The optimal timing of pancreatic enzyme replacement therapy (PERT) after pancreatic surgery for pancreatic cancer remains uncertain. We compared outcomes after early versus delayed PERT initiation in a real-world cohort. Methods: This retrospective cohort study used the TriNetX US Collaborative Network database. Adults with pancreatic cancer undergoing pancreatic surgery were categorized as early PERT if treatment was started within 1 month after surgery, and late PERT if started between 2 and 3 months after surgery. Outcomes were assessed from 90 to 730 days after the index event. Comparative analyses were performed after 1:1 propensity score matching. Results: Before matching, 3960 patients were identified in the late PERT cohort and 9807 in the early PERT cohort; after matching, 3948 patients were retained in each group. All-cause mortality was similar between the late and early PERT cohorts (1076/3871 [27.8%] vs. 1022/3831 [26.7%]; risk ratio [RR]: 1.042; 95% CI: 0.969-1.121; P =0.270; hazard ratio [HR]: 1.018; 95% CI: 0.935-1.109; log-rank P =0.677). Emergency department visits were also similar (35.7% vs. 34.3%; RR: 1.042; 95% CI: 0.981-1.107; P =0.179). Late PERT was associated with higher risk of diarrhoea (31.0% vs. 28.9%; RR: 1.072; 95% CI: 1.002-1.147; P =0.044) and albumin <3.5 g/dL (62.7% vs. 58.8%; RR: 1.066; 95% CI: 1.029-1.105; P <0.001; HR: 1.076; 95% CI: 1.017-1.139; log-rank P =0.011). Conclusions: Delayed PERT initiation was not associated with higher mortality or emergency department utilization but was associated with higher diarrhea and hypoalbuminemia risk.