Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Abstract

BackgroundImmune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these invasive procedures frequently can become cumbersome. We sought to assess the role of fecal calprotectin (FC) concentration as a non-invasive biomarker of endoscopic or histologic remission.MethodsWe performed a retrospective study of patients with IMDC who were tested for FC at IMDC onset and after IMDC treatment between June 2016 and March 2020. Patient demographics, clinical variables, and FC data were collected and analyzed to determine the optimal cut-off FC concentration to predict endoscopic and histologic remission.ResultsOur sample comprised 77 patients with a median age of 62 years; 66% were male and 94% were Caucasian. Sixty-five patients (84%) achieved clinical remission, 46 (60%) achieved endoscopic remission, and 24 (31%) achieved histologic remission after IMDC treatment. FC concentrations decreased from the time of IMDC onset to the end of treatment (p<0.001). High FC concentrations were associated with evident endoscopic inflammation (p=0.003) and acute/chronic active colitis (p=0.025) which positively correlated with the Mayo Endoscopic Subscore (r=0.615, p=0.001) at the time of IMDC onset. In patients who achieved endoscopic remission after treatment, a significantly lower FC concentration was observed at IMDC onset (p=0.006) and after treatment (p<0.001) compared with those without endoscopic remission. The cut-off FC concentration to predict endoscopic remission was ≤116 μg/g and for histologic remission ≤80 μg/g; these cut-offs had optimal specificity (94% and 85%, respectively) and positive predictive value (0.91 and 0.38, respectively).ConclusionsFC concentration may serve as a non-invasive biomarker to predict endoscopic and histologic remission in patients receiving treatment for IMDC, minimizing the need for frequent invasive endoscopies. Future prospective studies are needed to provide further insight on the role of this marker in disease surveillance.

Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis

“…Accordingly, levels of fecal calprotectin and lactoferrin correlate with endoscopic findings of ulceration and histological signs of IMC (107). Furthermore, fecal calprotectin is increased upon the onset of diarrhea and reduced when clinical remission is observed (108,109). This could therefore be a promising marker to monitor disease activity and relapse in patients, as already suggested in American Society of Clinical Oncology guidelines (110).…”

Flexible sigmoidoscopy may be sufficient for initial evaluation of suspected immunotherapy‐mediated colitis: A cross‐sectional study

“…Colonoscopy may still be useful in patients with treatment-refractory IMC as the presence of gross abnormalities in the proximal colon and persistent histologic evidence of IMC can inform the clinician's decision to initiate biologic therapy early in the treatment course. 7 Non-invasive biomarkers such as fecal calprotectin and lactoferrin have demonstrated utility in confirming the diagnosis of IMC [9][10][11] ; however, they are not routinely used to guide treatment. In addition, these biomarkers may not help identify alternative structural causes of gastrointestinal symptoms such as IMC with superimposed infection.…”

“…8 Furthermore, the diagnosis of IMC is often made clinically by the treating oncologist based on the presence of symptoms and as such, treatment with steroids is initiated without histological confirmation of the IMC diagnosis or use of non-invasive biomarkers such as fecal calprotectin or lactoferrin. [9][10][11] This common clinical scenario has the potential for missing alternative diagnoses such as infectious or radiation colitis and can lead to delays in escalation of therapy due to missed severe disease. 4,12 Endoscopic testing for IMC varies widely in clinical practice.…”

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

“…We found two patients with CIC had elevated fecal calprotectin (Figure 3C). Zou et al (159) retrospectively analyzed the fecal calprotectin of patients with CIC and found that it was increased at the onset of IMC while decreased after treatment. In terms of infectious pathogens, Clostridium difficile (C. difficile) was the most common pathogen.…”

“…LDH ≥618 IU/L was related to a poor prognosis in CIC patients (60). Conversely, the decrease of fecal calcitonin after treatment occurred more significantly in patients with CIC remission under endoscopy, which could be used as a non-invasive tool for monitoring and evaluating the response of CIC (159). Nevertheless, the value of fecal calcitonin was limited by its 54% specificity in predicting the endoscopic remission of CIC (166).…”