Here’s a startling fact: Cancer patients treated with immune checkpoint inhibitors (ICIs) who experience gastrointestinal side effects like diarrhea and colitis may face an unexpected double whammy—an increased risk of developing adenomas in the colon, potentially paving the way for colon cancer. But here’s where it gets controversial: While these side effects are well-documented, their long-term implications on colorectal health have only recently come under scrutiny, leaving many clinicians and patients in uncharted territory. New research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting sheds light on this critical issue, raising questions about surveillance strategies and patient care.
The Study’s Eye-Opening Findings
Led by Tanvi Gupta, MD, from The University of Texas Health Science Center, the study analyzed 248 cancer patients treated with ICIs who developed diarrhea and colitis. These patients underwent colonoscopies within 90 days of symptom onset and were followed up over time. The results were striking: Nearly 30% of patients developed adenomas—precancerous growths in the colon—with over 50% of these adenomas appearing rapidly, within just 7.5 months of experiencing ICI-related side effects. And this is the part most people miss: Even patients without a prior history of polyps faced a significantly higher risk of adenoma development if they experienced these gastrointestinal side effects.
Why This Matters
ICIs, such as PD-1 and PD-L1 inhibitors, have revolutionized cancer treatment, offering hope to patients with advanced malignancies. However, their off-target effects, particularly diarrhea and colitis, are believed to stem from excessive inflammation triggered by the therapy. While prolonged colitis has paradoxically been linked to improved cancer outcomes, the persistent inflammation poses serious risks, including damage to the colon’s lining. This damage, researchers argue, creates a fertile ground for adenomas to develop, potentially compounding the patient’s cancer burden.
The Role of Inflammation
One of the study’s most critical findings is the direct link between histological inflammation and adenoma development. Regardless of whether patients had pre-existing polyps, the presence of active inflammation significantly increased their risk. This suggests that the inflammatory process itself, rather than just the presence of polyps, drives mucosal injury and subsequent adenoma formation. Boldly put, this challenges the conventional wisdom that polyps are the primary precursor to adenomas, inviting a reevaluation of how we monitor these patients.
Implications for Surveillance
The findings have sparked a debate about how frequently these patients should be monitored. Danny Issa, MD, an interventional endoscopist at UCLA, emphasized the need for longer-term studies but acknowledged the study’s immediate impact: “It’s eye-opening for the many patients on these medications now.” Sita S. Chokhavatia, MD, a gastroenterologist, highlighted the alarming context: “These patients already have one type of cancer, and now they may face an increased risk of colon cancer. How often should we follow up on them?”
A Call to Action
Yinghong Wang, MD, PhD, the study’s senior author, recommended routine surveillance colonoscopies within one year of ICI-mediated diarrhea and colitis onset, with subsequent intervals based on initial findings. This proactive approach, she argues, is crucial given the rapid development of adenomas during this period. But here’s the question that lingers: Are we doing enough to balance the benefits of ICIs with the risks they pose to colorectal health? And should guidelines be updated to reflect these findings?
Food for Thought
As ICIs continue to transform cancer care, this study serves as a reminder that every treatment comes with trade-offs. While managing one cancer, are we inadvertently setting the stage for another? And how should clinicians weigh the benefits of these life-saving therapies against their long-term risks? We want to hear from you: Do these findings change how you view the use of ICIs? Share your thoughts in the comments below, and let’s spark a conversation that could shape the future of cancer care.
