Diagnostic Performance of Fecal Biomarkers and Their Correlation with Endoscopic Severity in Immune Checkpoint...

Immune-related adverse events (irAEs), which occur due to loss of immune tolerance, represent a significant challenge when using immune checkpoint inhibitors (ICIs). As the indications for ICIs continue to expand, the incidence of irAEs has been increasing. Immune-mediated diarrhea and colitis (IMDC) is one of the most frequent irAEs. Although important for the management of IMDCs, colonoscopy is highly invasive for patients with cancer, and development of noninvasive alternatives is needed.

We prospectively enrolled patients diagnosed with IMDC between May 2019 and May 2025, and a total of 34 patients were included in the final analysis. Blood and stool samples were collected, and biomarker levels were measured. Endoscopic activity was defined as a Mayo Endoscopic Subscore of ≥2, as evaluated during colonoscopy. The relationship of each biomarker with endoscopic activity was examined using Spearman's rank correlation and receiver operating characteristic curve analysis.

Fecal calprotectin (FC), fecal lactoferrin (FL), and fecal immunochemical test (FIT) were significantly correlated with the Mayo Endoscopic Subscore, with correlation coefficients of 0.50, 0.51, and 0.74, respectively. These biomarkers effectively detected endoscopic activity, with high area under the curve values of 0.79, 0.81, and 0.94, respectively. Furthermore, certain combinations of fecal biomarkers enhanced accuracy, as demonstrated by FC (+) or FIT (+), which achieved a sensitivity of 95.5% and a specificity of 75.0%.

Fecal biomarkers were correlated with endoscopic activity and effectively identified patients with endoscopically active IMDC. Our findings suggest that these biomarkers may be valuable tools for the diagnosis and assessment of treatment response in IMDC.