Association between pancreatic enzyme replacement therapy and mortality in pancreatic cancer: a matched case-control study

BACKGROUND: Malnutrition and pancreatic exocrine insufficiency (PEI) are common among patients with pancreatic cancer. Despite the potential of pancreatic enzyme replacement therapy (PERT) to correct PEI, its association with survival remains uncertain. Our study aimed to evaluate the trend in PERT prescription and its potential association with mortality among patients with pancreatic cancer. METHODS: We included patients with pancreatic ductal adenocarcinoma (PDAC) discussed at a tertiary hospital tumor board between 2008-2012 and 2015-2018. Cases (deceased within one year) were matched 1:1 with controls (alive at one year). Patients were classified as PERT users or non-users based on prescriptions after PDAC diagnosis. Conditional logistic regression assessed the association between PERT usage and all-cause mortality at one-year post-diagnosis. RESULTS: A total of 1247 patients were included: 756 (61 %) who died within one year and 491 (39 %) who survived. PERT prescriptions increased over time, particularly in the palliative setting (46 % vs. 75 %, p = 0.001). Matching yielded 487 pairs. In the full population, PERT use was associated with lower one-year mortality (adjusted OR 0.49, 95 %CI = 0.34-0.71). Similar associations were seen among subgroups undergoing surgery (aOR 0.34, 95 %CI = 0.16-0.74) and those receiving best supportive care (aOR 0.12, 95 %CI = 0.03-0.33). In the chemotherapy-only subgroup, the direction of effect suggested a potential risk reduction, but without statistical significance (aOR 0.75, 95 %CI = 0.44-1.24). CONCLUSION: There is an overall decrease in mortality among PERT-users compared to non-users. The results may be overly optimistic due to potential confounding factors related to patient selection, and randomized controlled studies are needed to confirm these effects.