Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but they frequently trigger gastrointestinal side effects—diarrhoea being among the most common. When such diarrhoea occurs, clinicians often measure faecal elastase to gauge pancreatic function.

However, a key limitation of this test is that watery stool can dilute elastase concentrations, potentially leading to misdiagnosis of pancreatic insufficiency.

Whether low faecal elastase in ICI-treated patients reflects genuine pancreatic dysfunction or merely stool dilution has remained unclear.

A new study made available online on July 16, 2026, in the Journal of Pancreatology set out to answer this question.

Researchers at The University of Texas MD Anderson Cancer Centre and the Cleveland Clinic retrospectively reviewed 388 patients treated with ICIs who developed diarrhoea and underwent faecal elastase testing between 2016 and 2024.

The team found that faecal elastase was low in 168 (43.3%) and normal in 220 patients (56.7%). Crucially, patients with low elastase had significantly higher faecal calprotectin levels (356.0 vs. 124.9 mcg/g), indicating greater gastrointestinal inflammation.

Yet on colonoscopy and histology, the rates of active inflammation were similar between the low- and normal-elastase groups.

Most importantly, diarrhoea outcomes were similar regardless of elastase status: remission occurred in 74.4% of patients with low elastase and 69.1% of those with normal levels.

Baseline pre‑existing pancreatic abnormalities were rare and unrelated to elastase levels, though new ICI‑related pancreatic injury was observed more frequently among patients with low elastase.

Together, these findings suggest that in ICI-related diarrhoea, low faecal elastase is more likely a dilutional artefact than evidence of true exocrine pancreatic insufficiency.

The authors recommend that when pancreatic disease is genuinely suspected, clinicians should consider confirmatory faecal fat testing before initiating pancreatic enzyme replacement therapy.

This highlights the need for comprehensive diagnostic approaches, including faecal fat testing, to confirm exocrine pancreatic insufficiency before starting enzyme therapy.

Article: Role of fecal elastase in the context of diarrhea related to immune checkpoint inhibitors

Source: Chinese Medical Journals Publishing House Co., Ltd.