Real-world management and outcomes of immune-mediated diarrhea and colitis: gaps in guideline adherence and opportunities for implementation

Abstract

Purpose

Immune-mediated diarrhea and colitis (IMDC) is a high-risk toxicity frequently experienced by patients treated with immune checkpoint inhibitors (ICIs) and requiring rapid supportive care interventions. Delays in IMDC reporting and inconsistent guideline adherence increase symptom burden and emergency department (ED) utilization. Although current practice guidelines provide IMDC management recommendations, adherence in routine oncology care remains uncertain. This study evaluated management and guideline concordance for clinically significant IMDC at a single National Cancer Institute–designated comprehensive cancer center to identify workflow opportunities to improve supportive management.

Methods

We conducted a retrospective observational study of adults treated with ICIs between 2011 and 2024 who developed IMDC requiring systemic immunosuppression. Electronic health record (EHR) data were used to characterize patient demographics, IMDC reporting patterns, and to assess National Comprehensive Cancer Network (NCCN) guideline concordance in terms of IMDC diagnostic workup and management across care settings.

Results

ED clinicians demonstrated greater adherence to NCCN guidelines than outpatient oncology providers. Of the 17 patients with IMDC, nine (52.94%) required ED management, with an average immunosuppressive therapy duration of 92.29 days, and only four (23.53%) resumed ICI therapy following IMDC resolution. Despite 88.24% of patients presenting with moderate-severe IMDC, 41.18% experienced symptoms for over a week before seeking medical care. Over 40% of patients with IMDC experienced concurrent immune-related adverse events (irAEs), with dermatitis and hepatitis being the most common.

Conclusion

Our findings reveal actionable targets for improving supportive management of clinically significant IMDC. Implementing standardized workflows and decision-support tools may strengthen evidence-based IMDC care, reduce treatment delays, and improve patient outcomes.

Background

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy across tumor types and treatment settings. While generally well tolerated, ICIs can lead to immune-related adverse events (irAEs) that can affect any organ system and vary in severity. Immune-mediated Diarrhea and Colitis (IMDC) is the second most prevalent and clinically significant irAE after immune-mediated dermatitis [1, 2] and is a common reason for discontinuing ICI therapy [3, 4].

IMDC typically presents with symptoms of watery diarrhea, cramping, urgency, abdominal pain, blood and mucus in the stool, fever, and nocturnal bowel movements [5], often accompanied by abnormal endoscopic [6–9] and radiologic [10] findings and elevated fecal calprotectin and lactoferrin [11]. IMDC varies from mild to life-threatening in terms of severity and can develop rapidly [12, 13] or several months after the last exposure to ICI therapy [14]. This variability in presentation and onset complicates the timely diagnosis and management of IMDC, making it a critical concern in oncology practice.

The National Comprehensive Cancer Network (NCCN) has established evidence-based guidelines, detailed in Table 1 [5] for the classification, diagnostic workup, and management of IMDC, including corticosteroid initiation thresholds, use of second-line immunosuppressants, and criteria for ICI rechallenge. Moderate-severe IMDC (grades 2–4) carries the greatest clinical consequences, often requiring systemic immunosuppression and interruption of ICI therapy. At present, little is known about how closely these guidelines are followed in everyday oncology practice or whether care delivery differs across clinical settings.

Table 1.

IMDC Classification and management recommendations

IMDC Grade	Grade 1 (Mild)	Grade 2 (Moderate)	Grades 3–4 (Severe)
Classification	< 4 bowel movements (BMs)/day above baseline and no colitis symptoms	4–6 BMs/day above baseline colitis symptoms, not interfering with activities of daily living (ADLs)	> 6 BMs/day above baseline, colitis symptoms, interference with ADLs, hemodynamic instability, hospitalization, serious complications
Workup	Consider stool evaluation to rule out infectious etiology. Consider fecal lactoferrin/calprotectin	Stool evaluation to rule out infectious etiology. Consider fecal lactoferrin/calprotectin. Consider abdominal/ pelvic CT with contrast. Consider GI consultation	Stool evaluation to rule out infectious etiology. Consider fecal lactoferrin/calprotectin. Consider abdominal/ pelvic CT with contrast. Recommend GI consultation
Management	Consider holding ICI therapy. Consider antidiarrheal agents and dietary modifications for 2–3 days for symptom relief. If no improvement, obtain infectious workup. If persistent/progressive symptoms, check lactoferrin/calprotectin	Hold ICI therapy. Administer systemic corticosteroids (prednisone/IV methylprednisolone 1–2 mg/kg/day). If no response to steroids, consider adding infliximab or vedolizumab	Follow Grade 2 IMDC management steps. G3 – consider resuming anti-PD-1/anti-PD-L1 therapy after resolution of toxicity. G4 – permanently discontinue ICI therapy Consider inpatient care for provision of supportive care

Adapted from National Comprehensive Cancer Network. Management of Immunotherapy-Related Toxicities (Version 1.2026). NCCN Clinical Practice Guidelines in Oncology. Published 2026. Accessed February 26, 2026. https://www.nccn.org

This retrospective observational study evaluated management of clinically significant IMDC among patients treated with ICIs at a single NCI-designated comprehensive cancer center. The objective was to examine patterns in IMDC presentation, symptom reporting, diagnostic workup, and management, and to assess their alignment with current NCCN recommendations. By characterizing variability in real-world IMDC practices, this study seeks to support the development of standardized clinical workflows and proactive education strategies for both patients and oncology care teams to improve timely recognition and management of IMDC.

Methods

Study design and participants

This retrospective observational study, conducted at an NCI-designated comprehensive cancer center in the Mountain West region of the United States, was designed to assess real-world IMDC diagnostic and management practices and evaluate their concordance with the NCCN practice guidelines. Routinely collected retrospective electronic health record data were analyzed without additional data manipulation. The institutional review board approved the study protocol (IRB #00176995) and granted a waiver of informed consent under 45 CFR 46.116(f) and 45 CFR 164.512(i)(2)(ii).

Patient identification

We abstracted electronic health records of individuals with non-small cell lung cancer (NSCLC) who met the following criteria: aged 18 or older, with at least one documented exposure to ICI therapy, administered either as a single agent or in combination with other ICI or chemotherapy. Additionally, selected individuals had diagnostic codes suggestive of IMDC attached to their EHR encounters. These diagnostic codes included descriptions such as “toxic gastroenteritis and colitis,” “noninfective gastroenteritis and colitis,” “diarrhea,” and “abdominal pain” and were accompanied by a prescription or administration record for systemic corticosteroids or immunosuppressive agents, such as infliximab, or vedolizumab.

The initial dataset included 417 patients, of whom 407 had received ICI therapy either alone or in combination with chemotherapy. Among these, 204 individuals had systemic corticosteroids (prednisone, methylprednisolone) or monoclonal antibody therapies (infliximab, vedolizumab) listed in their medication records. After excluding records without documented administration or prescription dates, we identified patients with diagnostic codes suggestive of IMDC and documented within 0–14 days of the initiation of immunosuppressive therapy. This filtering process resulted in 42 distinct patient records. Each case was then manually reviewed in the electronic health record (EHR) system using the patient’s medical record number. Patients who either experienced a different ICI-induced toxicity or had no clearly documented adverse event associated with immunosuppressive therapy during the relevant timeframe were excluded (n = 25). This comprehensive review resulted in a final dataset of 17 individuals, all confirmed to have experienced IMDC requiring systemic immunosuppression, as verified by encounter notes, diagnostic imaging, and laboratory data.

Data collection and variables

EHR data were manually abstracted using an institutionally hosted REDCap electronic data capture tool [15] and stored on HIPAA-protected Box servers. Extracted variables included patient demographic characteristics, IMDC presenting symptoms and reporting patterns, initial diagnostic workup, and IMDC management details such as type, dose, and duration of immunosuppressive therapy. Guideline concordance was evaluated across key NCCN-defined domains: documentation of symptom grade; completion of recommended diagnostic workup (infectious stool studies, imaging, or endoscopy, as appropriate); corticosteroid initiation and dosing; and appropriate ICI hold, discontinuation, or rechallenge. The NCCN grading definitions and corticosteroid initiation thresholds for IMDC remained consistent throughout the study period. To reduce misclassification and abstraction error, a second reviewer (KS) independently re-abstracted a random sample (target concordance ≥ 80%) [16], with 100% agreement achieved on reviewed key variables (presenting symptoms, diagnostic workup, patient outcomes).

Analysis

Descriptive statistics summarized patient characteristics, IMDC reporting, and management patterns. Analyses were descriptive and limited to available data. Missing values (e.g., unassessed laboratory or diagnostic tests) are indicated in the tables, and no data were imputed. Findings were interpreted thematically to identify practice variation and deviations from NCCN recommendations in both outpatient and ED care settings.

Results

Of the 17 patients with IMDC requiring systemic immunosuppression, 70.59% (n = 12) were white males with a mean age of 66.8, either current or former smokers, and had metastatic lung cancer. A total of nine (52.94%) patients had an ECOG performance status of 0 or 1, while six (35.29%) had an ECOG of 2. Only two patients had an ECOG of 3 or 4. Most patients (70.59%) were overweight (BMI = 25–30) or obese (BMI > 30).

More than half of the IMDC cohort received pembrolizumab either as monotherapy or in combination with chemotherapy (predominantly carboplatin and pemetrexed). The remaining individuals received nivolumab or atezolizumab, either as a single agent or in combination with targeted chemotherapy. Over 40% (n = 7) of individuals with IMDC had prior chemotherapy, while 17.65% had been previously treated with immune therapy, most receiving treatment with curative intent at initial diagnosis.

Hypertension (76.47%), chronic pain (52.94%), obesity (29.41%), and depression (29.41%) were common comorbidities. Common systemic medications among the IMDC cohort included antihypertensive medications (70.59%), proton pump inhibitors (64.71%), opioid analgesics (58.82%), non-steroidal anti-inflammatory medications (52.94%), and antidepressants (41.18%). Notably, none of the patients had a history of inflammatory bowel disease, and only one was previously diagnosed with rheumatoid arthritis. Table 2 further details the demographic characteristics of the IMDC cohort.

Table 2.

Key demographic characteristics of patients with IMDC

Characteristic	Categories	Patients (n = 17)
Gender	Male	12 (70.59%)
	Female	5 (29.41%)
Age at IMDC Onset	Range	47–85
	Mean	66.76
	Median	66
Ethnicity	White or Caucasian	14 (82.35%)
	Black or African American	1 (5.88%)
	Hispanic	1 (5.88%)
	Other	1 (5.88%)
Primary Health Insurance	Commercial Health Plan	8 (47.06%)
	Medicare	5 (35.29%)
	Other	3 (17.65%)
	Medicaid	1 (5.88%)
Smoking Status	Former Smoker	11 (64.71%)
	Never Smoker	4 (23.53%)
	Current Smoker	2 (11.76%)
Body Mass Index	18.5–25	5 (29.41%)
	25–30	4 (23.53%)
	> 30	8 (47.06%)
ECOG Status	0	4 (23.53%)
	1	5 (29.41%)
	2	6 (35.29%)
	3	1 (5.88%)
	4	1 (5.88%)
NSCLC Type	Adenocarcinoma	11 (64.71%)
	Squamous Cell	5 (29.41%)
	Poorly Differentiated	1 (5.88%)
NSCLC Stage	II	2 (11.76%)
	III	1 (5.88%)
	IV	14 (82.35%)
ICI Regimen	Pembrolizumab + Chemotherapy	8 (47.068%)
	Pembrolizumab Monotherapy	3 (17.65%)
	Nivolumab Monotherapy	2 (11.76%)
	Atezolizumab + Chemotherapy	2 (11.76%)
	Atezolizumab Monotherapy	1 (5.88%)
	Ipilimumab + Chemotherapy	1 (5.88%)
Prior Chemotherapy Exposure	Yes	7 (41.18%)
	No	10 (58.82%)
Prior ICI Therapy Exposure	Yes	3 (17.65%)
	No	14 (82.35%)
Systemic Medications	Antihypertensive Medications	12 (70.59%)
	Proton Pump Inhibitors	11 (64.71%)
	Opioid Analgesics	10 (58.82%)
	NSAIDs	9 (52.94%)
	Antidepressants	7 (41.18%)
	Antibiotics	5 (29.41%)
	Anxiolytics	5 (29.41%)
	Psychotropic Medications	3 (17.65%)
	Vitamin B Supplements	3 (17.65%)
	Vitamin D Supplements	2 (11.76%)
	Antidiabetic Medications	2 (11.76%)
Documented Comorbidities	Hypertension	13 (76.47%)
	Chronic Pain	9 (52.94%)
	Obesity	5 (29.41%)
	Depression	5 (29.41%)
	Anxiety	4 (23.53%)
	Diabetes	4 (23.53%)
	Weight Loss	2 (11.76%)
	Decreased Mobility	2 (11.76%)
	Hearing Loss	1 (5.88%)

Fifteen (88.24%) out of the 17 patients were exposed to ICI therapy for at least 30 days, with 35.29% receiving ICI therapy for over 180 days. While 76.47% of patients experienced IMDC symptoms within 90 days of their last ICI infusion, four patients had delayed-onset IMDC, occurring up to 370 days after their final ICI exposure.

In terms of IMDC symptom reporting, 13 out of 17 patients reported IMDC symptoms within 21 days of onset. However, four individuals had untreated low-grade diarrhea for extended periods, in some cases lasting as long as one year. The outpatient oncology clinic and emergency department (ED) were the primary settings for the initial evaluation of IMDC, with 64.71% (n = 11) and 23.53% (n = 4) of patients assessed in these settings, respectively. However, five of 13 patients with IMDC initially seen in an outpatient setting were later assessed at the ED. Only two patients contacted the outpatient oncology triage line to report their symptoms.

All patients reported diarrhea as their chief complaint, with 88.24% presenting with moderate or severe IMDC per NCCN grading criteria. Other common symptoms included weight loss (41.18%) and nausea and/or vomiting (35.29%), while blood-tinged stools were reported by only 11.76% of patients. Additionally, 47.06% of patients had attempted an unsuccessful trial of the over-the-counter antidiarrheal agent Imodium (loperamide) before seeking medical care. Notably, 41.18% of patients developed other concurrent irAEs, with autoimmune dermatitis and hepatitis being the most prevalent. Table 3 provides an overview of IMDC presenting symptoms and reporting patterns.

Table 3.

IMDC clinical presentation and reporting patterns

Parameter	Categories	Patients (n = 17)
ICI therapy exposure duration (days)	< 30	2 (11.76%)
	30–90	6 (35.29%)
	91–180	3 (17.65%)
	> 180	6 (35.29%)
Days elapsed between last ICI dose and IMDC symptom onset	< 15	4 (23.53%)
	15–30	5 (29.41%)
	31–90	4 (23.53%)
	> 90	4 (23.53%)
Days elapsed between IMDC symptom onset and report	< 7	10 (58.82%)
	7–21	3 (17.65%)
	> 21	4 (23.53%)
Setting of Initial IMDC evaluation	Outpatient Clinic Visit	11 (64.71%)
	ED Evaluation	4 (23.53%)
	Oncology Triage	2 (11.76%)
IMDC presenting symptoms	Diarrhea	17 (100.00%)
	Weight Loss	7 (41.18%)
	Nausea and/or Vomiting	6 (35.29%)
	Abdominal Pain	5 (29.41%)
	Nocturnal Diarrhea	4 (23.53%)
	Stool Incontinence	3 (17.65%)
	Blood in Stool	2 (11.76%)
IMDC severity (based on number of bowel movements/day)	Mild (< 4)	2 (11.76%)
	Moderate (4–6)	8 (47.06%)
	Severe (> 6)	7 (41.18%)
Trial of Imodium	Yes	8 (47.06%)
	No/Unknown	9 (52.94%)
Concurrent irAEs	Yes	7 (41.18%)
	No/Unknown	10 (58.82%)

Overall, 52.94% (n = 9) of patients with IMDC were evaluated at the ED, four at initial onset and five for subsequent symptom management. Three out of four patients (75%) initially evaluated at the ED were started on the appropriate dose of systemic corticosteroids, with an average dose of 0.89 mg/kg/day, and two had diagnostic imaging and stool tests ordered. One patient, seen at a different ED location, had incomplete records on the extent of IMDC workup but was initiated on appropriate corticosteroid therapy. Additionally, two patients with severe symptoms initially seen in the oncology clinic were referred to the ED the same day, where they received diagnostic imaging, stool marker assessments, and immunosuppression consistent with NCCN recommendations. Only one ED-assessed patient did not receive adequate management, instead being given fluids, electrolytes, and Imodium despite severe symptoms.

In contrast, of the 13 patients initially evaluated in the outpatient setting, only one had stool markers, and diagnostic imaging ordered the same day (excluding the two referred to the ED). However, three of these patients had undergone comprehensive imaging, including scans of the abdomen and pelvis, shortly before the onset of IMDC symptoms. Although 11 of 13 individuals (84.62%) evaluated in the oncology clinic reported moderate or severe symptoms, only four (30.78%) were started on systemic corticosteroids the same day, all at a dose below the 1 mg/kg/day recommended by the NCCN (mean = 0.64 mg/kg/day). The remaining seven patients managed in an outpatient setting were initially advised to use Imodium, though all eventually required systemic corticosteroids, and one case necessitated infliximab. Additionally, three individuals assessed in the oncology outpatient clinics received a dose of ICI therapy despite reporting moderate IMDC symptoms. Table 4 summarizes adherence to NCCN guideline–recommended practices across ED and outpatient oncology settings.

Table 4.

IMDC diagnostic workup and clinical course

Parameter	Categories	Patients (n = 17)
C. difficile and stool pathogens	Assessed	8 (47.06%)
	Not assessed	9 (52.94%)
Stool calprotectin	Assessed	5 (29.41%)
	Not assessed	12 (70.59%)
Stool lactoferrin	Assessed	4 (23.53%)
	Not assessed	13 (76.47%)
Abdominal imaging	Ordered	7 (41.18%)
	Not ordered	10 (58.82%)
Gastroenterology consult	Requested	2 (11.76%)
	Not requested	15 (88.24%)
Required ED management	Yes	9 (52.94%)
	No	8 (47.06%)
Days elapsed between initial evaluation and steroid therapy initiation	0	8 (47.06%)
	1–7	6 (35.29%)
	> 7	3 (17.65%)
Initial corticosteroid type and route	Prednisone PO	13 (76.47%)
	Methylprednisolone IV	3 (17.65%)
	Methylprednisolone PO	1 (5.88%)
Initial corticosteroid dose	< 1 mg/kg/day	7 (41.18%)
	1 mg/kg/day	8 (47.06%)
	2 mg/kg/day	2 (11.76%)
Infliximab or vedolizumab immunosuppression required?	Yes	1 (5.88%)
	No	16 (94.12%)
Refractory diarrhea following steroid taper?	Yes	5 (29.41%)
	No	12 (70.59%)
Immunosuppressive therapy duration (mean = 92.29 days)	< 30 days	2 (11.76%)
	30–60 days	7 (41.18%)
	61–90 days	6 (35.29%)
	> 90 days	2 (11.76%)
Supportive therapy	Bactrim	8 (47.06%)
	Proton Pump Inhibitor	13 (76.47%)
	Imodium	15 (88.24%)
Was ICI therapy interrupted at IMDC onset?	Yes	10 (58.82%)
	No	4 (23.53%)
	Not applicable	3 (17.65%)
Was ICI therapy resumed after IMDC resolution	No	10 (58.82%)
	Yes	4 (23.53%)
	Not applicable	3 (17.65%)
Was clinical rationale provided for discontinuing/resuming ICI therapy?	Yes	11 (64.71%)
	No	6 (35.29%)
Were NCCN guidelines referenced in clinical notes?	Yes	0 (0.00%)
	No	17 (100.00%)

Among the eight patients tested for C. difficile and other common pathogens, all had negative stool findings. In contrast, all patients who had inflammatory stool markers assessed had elevated calprotectin (5/5) and positive lactoferrin (4/4). Of the seven CT scans conducted as part of the IMDC evaluation or shortly before symptom onset, four revealed bowel wall thickening and edema. Only two patients (11.76%) underwent diagnostic colonoscopy, with one revealing lymphocytic colitis and the other showing no abnormal findings.

Nearly half (47.06%) of patients were started on systemic corticosteroids the day they first reported IMDC symptoms. The remaining 52.94%, predominantly those with mild to moderate IMDC, were initially managed conservatively with Imodium and dietary modifications before progressing to steroid therapy. Oral prednisone was the initial therapy in 76.47% of cases, while the remaining 23.53% received intravenous or oral methylprednisolone. Bactrim was prescribed in 47.06% of cases for P. jirovecii pneumonia prophylaxis, and 76.47% of patients were on concurrent proton pump inhibitor therapy, either initiated with steroids (11.76%) or continued from an existing prescription (64.71%). Imodium was recommended in 88.24% of cases as an adjunct for symptom management.

While only one patient required additional immunosuppression, first with infliximab and later with vedolizumab, 29.41% of patients experienced refractory diarrhea after initiating steroid taper, requiring a dose increase. No patients required colectomy during the study period, and no prolonged inpatient management for IMDC was documented in the available records. Overall, 88.24% of patients remained on immunosuppressive therapy for at least 30 days, with only two patients undergoing rapid steroid taper.

At the time of IMDC diagnosis, 58.82% had their ICI therapy suspended or permanently discontinued, while four patients continued ICI treatment either until symptom progression or, in mild cases, while on immunosuppressive therapy. Only four patients (23.53%) resumed ICI therapy upon IMDC resolution, all receiving the same ICI as before. One individual who developed IMDC following the completion of ICI therapy continued with surveillance following IMDC resolution. Of the 12 patients (70.59%) who permanently discontinued ICI therapy, three (25%) transitioned to Hospice, two (16.67%) experienced disease progression and were switched to chemotherapy, one patient (8.33%) who was on a combination ICI plus targeted agent regimen continued the targeted agent without resuming the ICI, four individuals (33.33%) whose disease remained stable off treatment transitioned to surveillance. The remaining two patients were changed to alternative non-ICI therapies. Table 4 provides an overview of IMDC diagnostic workup and clinical course.

Discussion

Results summary and interpretation of findings

In this single-institution cohort of patients with clinically significant IMDC, we observed significant variation in diagnostic workup and management practices. Patients evaluated in the ED generally received care more consistent with NCCN clinical guidelines [5] than those initially managed in the outpatient oncology setting. Specifically, seven of 13 patients initially seen in the outpatient clinic were started on Imodium before progressing to systemic corticosteroids, and three received an additional dose of ICI therapy despite reporting moderate IMDC symptoms.

The discrepancies observed between ED and outpatient management approaches may reflect variation in available resources, clinical workflows, or documentation practices across care settings. Additionally, ED clinicians may adhere more strictly to clinical algorithms, whereas clinicians in oncology outpatient clinics may have more flexibility in tailoring management strategies to individual patient needs and goals of care. Delayed IMDC management in outpatient clinics may also occur when IMDC symptoms are confused with chemotherapy-related toxicities in patients receiving concurrent ICI and chemotherapy, leading to missed guideline-recommended interventions and complicating timely oncology triage. Finally, deviation from NCCN recommendations may also reflect individualized clinical judgement in complex situations where standardized algorithms do not fully capture patient-specific considerations.

Similar to prior reports demonstrating frequent elevations of inflammatory stool markers in IMDC [17, 18], calprotectin and lactoferrin were abnormal in all patients tested in our cohort (calprotectin 5/5, lactoferrin 4/4). Abnormal imaging and endoscopic findings consistent with IMDC were variable among the limited number of patients who underwent these evaluations (CT: 4/7, colonoscopy: 1/2).Given the small numbers and non-systematic testing patterns, these results should be interpreted descriptively rather than as comparative assessments of diagnostic performance. Additionally, delayed-onset IMDC, occurring > 90 days after the last ICI exposure, was observed in 23.53% of patients, supporting the NCCN recommendation to follow patients previously treated with ICIs for at least two years [5].

Hypertension was present in over 76% (n = 13) of individuals who experienced IMDC. Previous studies examining the relationship between common comorbidities and the incidence of immune-related adverse events (irAEs) have also identified hypertension as a potential risk factor [19–21]. Additionally, 10 of 17 patients had opioid analgesics and nine had non-steroidal anti-inflammatory drugs (NSAIDs) on their medication list. This finding aligns with studies reporting that opioid analgesics [22, 23] and NSAIDs [19] may have immunosuppressive effects, potentially increasing the risk of irAEs. However, in the absence of a comparator group, these findings should not be interpreted as evidence of causal association but rather as observations that warrant further evaluation in larger, controlled studies.

In line with prior reports [24, 25], 76.47% of patients remained on immunosuppressive therapy for 30–90 days, with a few outliers either requiring extended immunosuppression or responding to a rapid taper. Notably, 41.18% of patients with IMDC were diagnosed with co-occurring irAEs, predominantly immune-mediated dermatitis. This finding closely aligns with previously published studies [5, 26], highlighting the need for heightened vigilance in monitoring for additional irAEs in patients with IMDC and reinforcing the importance of comprehensive management strategies to address concurrent irAEs.

Lastly, only two out of 17 patients (11.76%) reported their IMDC symptoms directly to their oncology team. Moreover, 41.18% of patients experienced symptoms for more than seven days before seeking medical evaluation. While descriptive, these findings highlight potential gaps in symptom reporting and patient education on common irAE presentations and timely symptom reporting, which may represent actionable targets for workflow improvement.

Importantly, these findings reflect practice patterns within a single academic center and should be interpreted as hypothesis-generating. This study was not designed to assess incidence, comparative effectiveness, or causal relationships between patient characteristics and IMDC outcomes.

Strengths and limitations

By focusing on the diagnostic workup and management of clinically significant IMDC in a real-world clinical setting, this research adds valuable insights into the practical management of IMDC, which has not been extensively studied. The in-depth qualitative review of patient records allows for a nuanced understanding of symptom presentation, diagnostic workup, and clinical decision-making, enhancing our understanding of IMDC beyond what quantitative studies alone can reveal.

However, several limitations must also be acknowledged. First, the study was conducted at a single site, which may limit the generalizability of its findings. Second, the absence of a comparison group prevents assessment of whether specific demographic and clinical characteristics correlate with an increased risk of IMDC. Third, the relatively small patient cohort (n = 17) limits the statistical power of the analysis and may introduce bias in capturing the full range of IMDC presentations and outcomes. The small sample size also reduces the ability to perform detailed subgroup analyses, which could have provided more granular insights into specific treatment approaches and patient outcomes. Accordingly, the findings are best interpreted as exploratory and intended to inform future multi-site investigations of IMDC management practices.

Conclusion

Within this single academic center cohort, we identified significant variation in the diagnostic workup and management of IMDC, with clinicians in the emergency department adhering more closely to clinical guidelines than those in outpatient settings. These insights underscore the need for a better understanding of real-world IMDC management and the factors contributing to deviations from established guidelines.

Future research should focus on conducting large, multisite studies to gain a more comprehensive understanding of IMDC across diverse patient populations and clinical settings. A larger sample size would also enable more detailed subgroup analyses, potentially providing valuable insights into specific risk factors associated with IMDC.

Additionally, focused group interviews with oncology and acute care clinicians could help uncover the reasons for deviations from clinical guidelines and lay the foundation for expert panels to review, update, and disseminate best practices. Future work should also incorporate structured implementation strategies, such as standardized triage pathways, embedded stool test order panels, and EHR prompts for IMDC grading, to support prompt, guideline-concordant care. Automated patient messaging systems to flag early-onset diarrhea symptoms and IMDC checklists within oncology clinics may further streamline symptom identification and management, improving consistency across care settings.

Collectively, these workflow-integrated approaches can strengthen adherence to evidence-based IMDC management, support more timely and consistent diagnosis and treatment, and ultimately enhance the safety of immunotherapy delivery.

Relevance to supportive oncology

Timely recognition and evidence-based management of IMDC are essential to prevent avoidable symptom burden, emergency care utilization, and treatment interruptions. Identifying workflow gaps and opportunities for standardized triage and decision-support can strengthen supportive care processes for patients receiving immunotherapy.

Abbreviations

ICI

Immune Checkpoint Inhibitor

IMDC

Immune-Mediated Diarrhea and Colitis

NCI

National Cancer Institute

EHR

Electronic Health Record

NCCN

National Comprehensive Cancer Network

ED

Emergency Department

irAEs

Immune-Related Adverse Events

Author contributions

- Natalya Alekhina: Conceptualization, Methodology, Data Preprocessing, Formal Analysis, Writing – Original Draft, Writing – Review and Editing—Kathi Mooney: Conceptualization, Methodology, Writing – Review and Editing, Supervision—Katherine Sward: Conceptualization, Methodology, Data Preprocessing, Writing – Review and Editing—Bob Wong: Methodology, Formal Analysis, Writing – Review and Editing—Wallace Akerley: Methodology, Writing – Review and Editing.

Funding

None.

Data availability

De-identified data available upon reasonable request.

Declarations

Ethics approval and consent to participate

The institutional review board approved the study protocol (IRB #00176995) and granted a waiver of informed consent under 45 CFR 46.116(f) and 45 CFR 164.512(i)(2)(ii).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.