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Objectives  Metachronous liver metastasis (LM) significantly impacts the prognosis of stage I-III colorectal cancer (CRC) patients. An effective biomarker to predict LM after surgery is urgently needed. We aimed to develop deep learning-based models to assist in predicting LM in stage I-III CRC patients using digital pathological images.    Methods  Six-hundred eleven patients were retrospectively included in the study and randomly divided into training (428 patients) and validation (183 patients) cohorts according to the 7:3 ratio. Digital HE images from training cohort patients were used to construct the LM risk score based on a 50-layer residual convolutional neural network (ResNet-50). An LM prediction model was established by multivariable Cox analysis and confirmed in the validation cohort. The performance of the integrated nomogram was assessed with respect to its calibration, discrimination, and clinical application value.    Results  Patients were divided into low- and high-LM risk score groups according to the cutoff value and significant differences were observed in the LM of the different risk score groups in the training and validation cohorts ( P &amp;lt;0.001). Multivariable analysis revealed that the LM risk score, VELIPI, pT stage and pN stage were independent predictors of LM. Then, the prediction model was developed and presented as a nomogram to predict the 1-, 2-, and 3-year probability of LM. The integrated nomogram achieved satisfactory discrimination, with C-indexes of 0.807 (95% CI: 0.787, 0.827) and 0.812 (95% CI: 0.773, 0.850) and AUCs of 0.840 (95% CI: 0.795, 0.885) and 0.848 (95% CI: 0.766, 0.931) in the training and validation cohorts, respectively. Favorable calibration of the nomogram was confirmed in the training and validation cohorts. Integrated discrimination improvement and net reclassification index indicated that the integrated nomogram was superior to the traditional clinicopathological model. Decision curve analysis confirmed that the nomogram has clinical application value.    Conclusions  The LM risk score based on ResNet-50 and digital HE images was significantly associated with LM. The integrated nomogram could identify stage I-III CRC patients at high risk of LM after primary colectomy, so it may serve as a potential tool to choose the appropriate treatment to improve the prognosis of stage I-III CRC patients.

Accurate Prediction of Metachronous Liver Metastasis in Stage I-III Colorectal Cancer Patients Using Deep Learning With Digital Pathological Images