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Simple Summary  Deep learning methods are increasingly being applied for tissue classification to improve diagnosis and optimize therapy stratification. In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups according to the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. For a validation collective ( n  = 128), we showed that BIg-CoMet was able to stratify patients appropriately. The predicted high-risk group showed a worse clinical course for being metastasis-free, and the risk group was a prognostic factor for the occurrence of metastasis. These results were also found for both Union Internationale Contre le Cancer (UICC) subgroups. We demonstrated that Big-CoMet is useful for the stratification of colon cancer patients into risk groups based on images reflecting tumor architecture.    Abstract  In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups for the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. We enrolled 291 colon cancer patients with pT3 and pT4 adenocarcinomas and converted one cytokeratin-stained representative tumor section per case into a binary image. Image augmentation and dropout layers were incorporated to avoid overfitting. In a validation collective ( n  = 128), BIg-CoMet was able to discriminate well between patients with and without metastasis (AUC: 0.842, 95% CI: 0.774–0.911). Further, the Kaplan–Meier curves of the metastasis-free survival showed a highly significant worse clinical course for the high-risk group (log-rank test:  p  < 0.001), and we demonstrated superiority over other established risk factors. A multivariable Cox regression analysis adjusted for confounders supported the use of risk groups as a prognostic factor for the occurrence of metastasis (hazard ratio (HR): 5.4, 95% CI: 2.5–11.7,  p  < 0.001). BIg-CoMet achieved good performance for both UICC subgroups, especially for UICC III ( n  = 53), with a positive predictive value of 80%. Our study demonstrates the ability to stratify colon cancer patients via a semi-guided process on images that primarily reflect tumor architecture.

Deep Learning Prediction of Metastasis in Locally Advanced Colon Cancer Using Binary Histologic Tumor Images