Revised Tumor Burden Score for Prognostic Stratification in Metastatic Colorectal Cancer Patients Receiving Immunotherapy: A Retrospective Study

BACKGROUND: Immunotherapy has improved outcomes in metastatic colorectal cancer (mCRC), but benefits remain largely restricted to the minority with specific biomarkers like microsatellite instability-high (MSI-H). This study aims to develop and validate a revised tumor burden score (rTBS) as a prognostic model to stratify survival outcomes in mCRC patients receiving immunotherapy. METHODS: We analyzed a retrospective cohort of 339 immunotherapy-treated mCRC patients (2019-2024). Univariable and multivariable Cox regression analysis were employed to identify independent prognostic factors and construct a model for progression-free survival (PFS). rTBS was developed by integrating CEA, metastatic organ count, and target lesion count. rTBS prognostic performance was validated via bootstrapping, internal and external dataset, ROC curves, and Kaplan-Meier analysis across MSI/TMB subgroups. RESULTS: Independent risk factors included TMB level, CEA, metastatic organ count, and target lesion count. The integrated rTBS outperformed TMB (AUC = 0.768 vs 0.656) and traditional metrics. Low rTBS patients showed superior PFS and overall survival (Both P < 0.0001), higher objective response rate (ORR: 37% vs 21.4%, P = 0.002) and disease control rate (DCR: 73.6% vs 51.1%, P < 0.0001). rTBS also stratified outcomes in both MSI-H/TMB-High and MSI-L/MSS/TMB-Low subgroups (Both P < 0.0001). Moreover, split-sample testing, external validation, and bootstrap analysis collectively demonstrated the model's robust validity. CONCLUSIONS: The rTBS is a robust, cost-effective prognostic model that stratifies survival in immunotherapy-treated mCRC across subtypes, particularly in the MSI-L/MSS/TMB-Low subgroup lacking reliable biomarkers. It bridges molecular heterogeneity and clinical practice, and warranting further multicenter validation. IMPLICATIONS FOR PRACTICE: The revised tumor burden score (rTBS) provides a clinically actionable, cost-effective tool to enhance prognostic stratification in patients with metastatic colorectal cancer (mCRC) receiving immunotherapy. By integrating routinely available metrics (CEA, metastatic organ count, and target lesions), rTBS achieves superior prognostic discrimination (AUC = 0.768) compared to traditional biomarkers such as TMB (AUC = 0.656) and consistently stratifies outcomes across molecular subtypes. Of particular clinical relevance, rTBS identifies patients with more favorable prognosis within the MSI-L/MSS/TMB-Low subgroup, addressing a major unmet need in this biomarker-limited population. It also refines risk stratification in MSI-H/TMB-High patients by identifying those with high tumor burden and poor prognosis. By leveraging readily accessible clinical and imaging data, rTBS circumvents the need for costly molecular profiling, bringing pragmatic risk stratification within reach even in resource-constrained settings. These findings position rTBS as a useful decision-support tool for prognostic evaluation, assisting clinicians in personalizing management strategies for mCRC.