When new therapies arrive, we should think more: The unseen challenges of immunotherapy-induced remodeling

Abstract

The paradigm-shifting efficacy of immune checkpoint inhibitors in microsatellite instability-high colorectal cancer demands a critical appraisal of their long-term tissue effects. This editorial is a landmark case report revealing spontaneous colonic transection following pathological complete response to pembrolizumab - a first-in-medicine finding. Despite radiological resolution of disease, profound immune-mediated tissue remodeling resulted in catastrophic structural failure at the tumor site. This phenomenon exposes critical limitations in current imaging modalities to detect immunotherapy-induced bowel wall fragility and necessitates heightened awareness among surgeons. As immune checkpoint inhibitors move into neoadjuvant settings with rising complete response rates, we must reassess surgical planning, consider prophylactic interventions for high-risk anatomy, and develop biomarkers for tissue integrity. This case underscores that tumor regression does not equate to restored organ function, urging multidisciplinary vigilance against delayed structural toxicity.

Keywords: Immune checkpoint inhibitors; Microsatellite instability-high colorectal cancer; Tissue remodeling; Pathological complete response; Toxicity

Core Tip: The unprecedented case of spontaneous colonic transection after pathological complete response to pembrolizumab in microsatellite instability-high colorectal cancer highlights a critical blind spot in immune oncology. While immune checkpoint inhibitors achieve remarkable tumor regression, they can induce profound bowel wall damage invisible to conventional imaging. This editorial calls for urgent multidisciplinary action: Re-evaluating surgical timing and techniques in immunotherapy responders, developing novel biomarkers to predict bowel wall integrity, and implementing enhanced surveillance protocols to prevent catastrophic complications from delayed tissue toxicity.