TNT with induction chemoimmunotherapy and long-course chemoradiation may lead to high CR in high-risk, pMMR rectal cancer. Both CD8IE and FoxP3IS showed independent prognostic value as RFS markers in bivariable and multivariable analyses. Nivolumab plus ipilimumab showed significant improvement in progression-free survival in patients in the first line setting. The ELI-002 vaccine uses T cells to identify and remove tumor cells containing KRAS G12D- or G12R-mutated cancer. GLP-1RAs are linked to a decreased risk of CRC compared with insulin and other antidiabetic drugs. Dr. Lieu discusses the CIRCULATE-NORTH AMERICA trial on ctDNA status as a biomarker for risk stratification in colon cancer. First-line nivolumab plus ipilimumab can act as a beneficial standard-of-care option for patients with MSI-H/dMMR mCRC. Colorectal cancer is now the leading cause of death for men and the second leading cause for women under 50 years of age. Prior research shows select patients with mCRC endure longer response to regorafenib while in clinical care settings. A novel combination regimen involving serplulimab may be a promising first-line treatment option for patients with mCRC. Highest-grade differentiation may reduce the risk of misclassifying cases as negative. Drs. Lidsky and Eng discuss PUMP, a phase 3 trial of HAI for treating patients with CRC and unresectable liver metastases. BMS announced that its phase 3 CheckMate 8HW trial in MSI-H or dMMR metastatic colorectal cancer met its primary end point. A retrospective cohort study examined the prevalence and reasons for an unsatisfactory FIT, a common CRC screening modality. Dr. Fakih details his study and the results of the effectiveness of sotorasib plus panitumumab for KRAS G12C-mutated CRC. Fruquintinib is the first targeted agent in more than a decade for mCRC regardless of biomarker status or prior therapy. Dr. Barnell describes the "ColoSense" test and the study that showed its superior sensitivity and specificity vs colonoscopy. Sotorasib plus panitumumab resulted in longer PFS than standard treatment, and toxic effects remained similar for each agent. The trial analyzed the sensitivity and specificity of an mt-sRNA test compared with the results of a colonoscopy. Researchers found no significant change in HRQOL and fatigue from randomization to 1 year.