Colon Cancer Stage Ii Amp Iii

The goal of this prospective, single-center, multi-cohort clinical trial is to evaluate the efficacy and safety of neoadjuvant Iparomlimab/Tuvonralimab combined with CAPEOX, with or without propranolol, in patients with locally advanced pMMR (MSS) colon cancer. The main questions it aims to answer are: * What is the major pathological response (MPR) rate after neoadjuvant treatment and curative surgery (e.g., ≤10% viable tumor cells in the resected primary tumor)? * What are the key secondary outcomes (e.g., R0 resection rate, tumor regression grade, objective response rate, disease-free survival) and the safety/tolerability profile of these neoadjuvant regimens? If there is a comparison group: Researchers will compare Cohort A (Iparomlimab/Tuvonralimab + CAPEOX) versus Cohort B (Iparomlimab/Tuvonralimab + CAPEOX + propranolol) to see whether adding propranolol improves pathological and clinical responses while maintaining acceptable safety. Participants will: * Receive neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX for a protocol-defined number of cycles, with or without propranolol depending on cohort assignment. * Undergo curative-intent surgical resection after completing neoadjuvant therapy. * Be followed for postoperative treatment, adverse events, and longer-term outcomes (e.g., recurrence and survival), and may contribute tumor/blood samples for exploratory biomarker analyses related to treatment response.

The goal of this interventional clinical trial is to compare the efficacy of neoadjuvant chemotherapy versus upfront surgery in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and elevated baseline CEA (\>5 ng/mL) undergoing curative-intent treatment. This single-center, open-label, randomized controlled study will evaluate 2-year disease-free survival (2y-DFS) as the primary endpoint, with all study-related procedures-including longitudinal ctDNA-based molecular residual disease (MRD) monitoring, Immunoscore assessment, tumor tissue sequencing, and surveillance imaging-provided at no cost to participants. The main questions it aims to answer are: * Does a treatment strategy involving neoadjuvant CAPOX followed by surgery improve 2y-DFS compared with upfront surgery followed by standard adjuvant chemotherapy? * Do postoperative ctDNA-MRD status and its longitudinal dynamics predict 2y-DFS? * Does combining ctDNA-MRD with Immunoscore enhance prognostic risk stratification for recurrence beyond either biomarker alone? Participants will: * Be randomized 1:1 (N=100) to one of two treatment pathways: * Arm A: Neoadjuvant CAPOX × 4 cycles → curative surgery (R0 planned) → postoperative management per standard practice * Arm B: Upfront curative surgery → postoperative standard adjuvant chemotherapy per guideline → routine surveillance * Undergo baseline assessments prior to treatment initiation, including blood draw, colonoscopy, primary tumor next-generation sequencing (for personalized ctDNA-MRD assay development), and Immunoscore testing-all provided free of charge as part of the study. * Provide postoperative blood samples for ctDNA-MRD testing at approximately postoperative day \~7 and day \~30 (before adjuvant therapy start, if applicable). * During follow-up, provide serial blood samples every 3 months, aligned with routine surveillance visits, for repeat ctDNA-MRD analysis. * Receive standard-of-care postoperative surveillance (including imaging and clinical evaluations) through 2 years, with all study-mandated assessments covered by the trial. This trial integrates clinical intervention with comprehensive biomarker profiling to determine whether early systemic therapy alters MRD dynamics and improves outcomes in high-risk, CEA-elevated colon cancer.