Dr. Nicholas Hornstein highlights how ESMO 2025 delivered several practice-changing moments in colorectal cancer, including the first meaningful step toward immunotherapy efficacy in microsatellite-stable disease with the STELLAR-303 trial. New data on ctDNA reinforce its growing role in risk stratification and trial selection, while pending studies may soon clarify how to intensify therapy for ctDNA-positive patients. Targeted therapies continue to reshape care, with major advances in KRAS- and BRAF-mutated disease and compelling first-line data from the BREAKWATER study. Perhaps most striking, short-course neoadjuvant immunotherapy in MSI-high tumors is redefining what “curative” treatment can look like, setting the stage for the next wave of innovation in 2026 and beyond.