Individualized risk prediction models for colorectal cancer (CRC) play a pivotal role in shaping risk-based screening approaches, garnering attention for use in informed decision making by patients and clinicians. While the incorporation of new predictors and the development of advanced yet complex prediction models can enhance model performance, their practical implementation in clinical settings remains challenging. This systematic review assessed individualized CRC risk prediction models for their validity and potential clinical utility. Utilizing the Cochrane Collaboration methods and PROBAST tool, we conducted comprehensive searches across key databases and risk of bias assessment, respectively. Out of 41 studies included evaluating 44 risk prediction models, 12 conventional and 3 composite models underwent external validation. All risk models exhibited varying discriminatory accuracy, with the area under the curve (AUCs) ranging from 0.57 to 0.90. However, most studies showed an unclear or high risk of bias, with concerns about applicability. Of the five models with promising clinical utility, only two underwent external validation and one employed a decision curve analysis. These models demonstrated a discriminating and well-calibrated performance. While high-performing CRC risk prediction models exist, a need for transparent reporting of performance metrics and their clinical utility persists. Further research on this area is needed to facilitate the integration of these models into clinical practice, particularly in CRC screening.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. While screening tools such as the fecal immunochemical test (FIT) aid in early detection, they do not provide insights into individual risk factors or strategies for primary prevention. This study aimed to develop and internally validate an interpretable machine learning-based model that estimates an individual’s probability of developing CRC using readily available clinical and lifestyle factors. Methods: We analyzed data from 154,887 adults, aged 55–74 years, who participated in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A risk prediction model was built using the Light Gradient Boosting Machine (LightGBM) algorithm. To translate these findings into clinical practice, we implemented the model into a risk estimator that categorizes individuals as average, increased, or high risk, highlighting modifiable risk factors to support patient–clinician discussions on lifestyle changes. Results: The LightGBM model incorporated 12 predictive variables, with age, weight, and smoking history identified as the strongest CRC risk factors, while heart medication use appeared to have a potentially protective effect. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.726 (95% confidence interval [CI]: 0.698–0.753), correctly distinguishing high-risk from average-risk individuals 73 out of 100 times. Conclusions: Our findings suggest that this model could support clinicians and individuals considering screening by guiding informed decision making and facilitating patient–clinician discussions on CRC prevention through personalized lifestyle modifications. However, before clinical implementation, external validation is needed to ensure its reliability across diverse populations and confirm its effectiveness in real-world healthcare settings.