Abstract: Objective To investigate the prognostic factors affecting immunotherapy combined with targeted therapy for mismatch repair⁃proficient (pMMR) advanced colorectal cancer (CRC) and to establish a nomogram prediction model. Methods The clinical data of patients with pMMR advanced CRC who received immunotherapy combined with targeted therapy at the end line of the Guangxi Medical University Cancer Hospital from January 2020 to January 2023 were retrospectively analyzed. Multivariable Cox regression analysis was performed to identify the factors affecting prognosis. The nomogram models were constructed to predict progress⁃free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC), consistency index (C⁃index) and calibration curve were used to evaluate the performance of the model. The scores of nomogram prediction were calculated, and the patients were divided into the high⁃risk group and the low⁃risk group by X⁃tile software. Kaplan⁃Meier curve was drawn and Log⁃rank test was conducted to compare the survival differences between the two groups. Results A total of 116 patients were included in this study. Cox regression analysis showed that body mass index (BMI)≥25 kg/m2 was an independent protective factor for OS (HR=0.431, 95%CI: 0.187-0.990), while the cancer⁃inflammation prognostic index (CIPI)≥828.8 was an independent risk factor (HR=1.820, 95%CI: 1.012-3.271). The carcinoembryonic antigen (CEA)>5 ng/mL (HR=2.448, 95%CI: 1.121-5.345) and systematic immune⁃inflammation index (SII)≥663.9 (HR=2.730, 95%CI: 1.205-6.183) were independent risk factors for PFS. In the PFS nomogram model, the C⁃index of the training set and the validation set were 0.625 and 0.601, respectively. The AUCs of the training set at 3, 6, and 12 months were 0.666, 0.639, and 0.811, respectively, and those of the validation set were 0.696, 0.647, and 0.588, respectively. In the OS nomogram model, the C⁃index of the training set and the validation set were 0.663 and 0.662, respectively. The AUCs of the training set at 6 and 12 months were 0.689 and 0.761, respectively, and those of the validation set were 0.726 and 0.691, respectively. The OS rate curve in the calibration plot was fitted well with the 45°diagonal, indicating that the nomogram model had good discrimination. The Log⁃rank test showed that the PFS rate and OS rate of the low⁃risk group were higher than those of the high⁃risk group ( all P<0.001 ). Conclusions The nomogram model based on prognostic factors such as BMI, CIPI, SII and CEA can effectively predict the prognosis of patients with CRC immunotherapy. BMI, CIPI, SII and CEA may be potential markers for evaluating the prognosis of CRC immunotherapy.

Key words: Colorectal cancer, Immunotherapy, Nomogram, Body mass index, Cancer?inflammation prognostic index