Evaluation of the Applicability of Synthetic Data in the Development of Colorectal Cancer Survival Prediction Models: External Validation of Advanced Machine Learning Models Based on National Cancer Data Center Data.

BACKGROUND: Limited data availability and privacy constraints hinder the development of robust survival prediction models for personalized treatment. Synthetic data offers a promising solution, preserving the statistical properties of real clinical data. OBJECTIVE: This study aimed to quantitatively assess the feasibility of using synthetic data for survival prediction by evaluating model transfer performance to real-world hospital data, with a focus on model transfer strategies. METHODS: We developed and validated colorectal cancer survival prediction models using the National Cancer Data Center (NCDC) synthetic data (30,683 patients from 3 Korean institutions) for pretraining and real hospital data (2170 patients from Hwasun Jeonnam University Hospital) for external validation. We evaluated 3 model transfer strategies-domain adaptation, zero-shot, and ensemble-using extreme gradient boosting (XGBoost) and light gradient boosting machine (LightGBM). In total, 48 model configurations were tested, defined by the combination of algorithms (LightGBM and XGBoost), sampling technique (no-sampling, random undersampling [RUS], and synthetic minority oversampling technique combined with edited nearest neighbors [SMOTEENN]), model type (baseline, domain adaptation, zero-shot, and ensemble), and optimization objective (area under the precision-recall curve [AUPRC] and F1). The outcome was 7-year overall survival, evaluated using the AUPRC and Brier scores. Performance was compared against a hospital-only baseline using absolute values and deltas (ΔAUPRC and ΔBrier). Differences and corresponding 95% CIs were estimated on the held-out test set using 2000 bootstrap samples. RESULTS: Zero-shot application reduced the AUPRC in most settings, and any marginal improvements observed in the remaining settings were not statistically significant. In contrast, the domain adaptation model improved AUPRC in 8/12 combinations, with 4 statistically significant gains; the best setting (XGBoost+RUS+F1 optimization) achieved AUPRC=0.5391 (Δ+0.1474; P<.001). The soft ensemble increased AUPRC in 7/12 combinations, with 3 statistically significant gains; the best setting (XGBoost+RUS+AUPRC optimization) achieved AUPRC=0.5060 (Δ+0.1258, P=.002). For calibration, Brier scores improved in most domain adaptation and ensemble combinations, with a substantial proportion reaching statistical significance. CONCLUSIONS: When domain adaptation using local hospital data was applied, the model pretrained on synthetic data exhibited similar performance to the hospital-only baseline across various settings. This study demonstrates the methodological utility of a model transfer approach using NCDC synthetic data in a setting with limited data sharing. At the same time, it clarifies that while synthetic data can serve as a complement to local clinical data, it is not a substitute for real-world clinical models.