Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis

Abstract

BackgroundMalnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer.MethodsA retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan–Meier and Cox regression; groups were compared using the log-rank test.ResultsOverall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28–100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19–9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0–211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4–114.6 days) (HR 2.117, 95% CI 1.493–3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55–4.11; P < 0.001).ConclusionsIn patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

The use of pancreatic enzyme replacement therapy in patients with a diagnosis of chronic pancreatitis and pancreatic cancer in the US is infrequent and inconsistent

“…One retrospective study suggested exocrine pancreatic insufficiency was associated with reduced survival in patients with chronic pancreatitis 39 . A number of cohort studies, 22,40,41 a population‐based cohort study, 26 and some small randomised trials 42,43 have assessed the benefit of PERT in patients with pancreatic cancer. While results are not uniform, the largest population‐based analysis 26 demonstrates significantly improved survival (adjusted survival 2.62‐fold greater than those not on PERT [95% CI 2.27‐3.02]).…”

Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer

“…Indeed, only patients with good strength can cope with polychemotherapy treatments such as Folfirinox and the gemcitabine-nab-paclitaxel combination. This was shown in a retrospective study of 160 patients with unresectable PC [53]. The authors reported a significantly prolonged survival in patients treated with CT and PERT versus CT alone, and this effect was most pronounced in patients with significant weight loss at diagnosis.…”

Editorial: management of exocrine pancreatic insufficiency remains a challenge—can we do better?

“…The gold standard, but difficult to perform, three‐day faecal fat test has now largely been replaced by spot faecal elastase assays. In EPI subjects, pancreatic enzyme replacement therapy (PERT) improves steatorrhoea, nutritional parameters, quality of life and mortality 5,6 . Two European observational studies in PC and CP reported under‐utilisation of pancreatic function testing and inadequate PERT dosing 7,8 …”