Artificial Intelligence for Prognostic Scores in Oncology: a Benchmarking Study

Introduction: Prognostic scores are important tools in oncology to facilitate clinical decision-making based on patient characteristics. To date, classic survival analysis using Cox proportional hazards regression has been employed in the development of these prognostic scores. With the advance of analytical models, this study aimed to determine if more complex machine-learning algorithms could outperform classical survival analysis methods. Methods: In this benchmarking study, two datasets were used to develop and compare different prognosticmodels for overall survival in pan-cancer populations: a nationwide EHR-derived de-identified database for training and in-sample testing and the OAK (phase III clinical trial) dataset for out-of-sample testing. A real-world database comprised 136K firstline treated cancer patients across multiple cancer types and was split into a 90% training and 10% testing dataset, respectively. The OAK dataset comprised 1,187 patients diagnosed with non-small cell lung cancer. To assess the effect of the covariate number on prognostic performance, we formed three feature sets with 27, 44 and 88 covariates. In terms of methods, we benchmarked ROPRO, a prognostic score based on the Cox model, against eight complex machine-learning models: regularized Cox, Random Survival Forests (RSF), Gradient Boosting (GB), DeepSurv (DS), Autoencoder (AE) and Super Learner (SL). The C-index was used as the performance metric to compare different models. Results: For in-sample testing on the real-world database the resulting C-index [95% CI] values for RSF 0.720 [0.716, 0.725], GB 0.722 [0.718, 0.727], DS 0.721 [0.717, 0.726] and lastly, SL 0.723 [0.718, 0.728] showed significantly better performance as compared to ROPRO 0.701 [0.696, 0.706]. Similar results were derived across all feature sets. However, for the out-of-sample validation on OAK, the stronger performance of the more complex models was not apparent anymore. Consistently, the increase in the number of prognostic covariates did not lead to an increase in model performance. Discussion: The stronger performance of the more complex models did not generalize when applied to an out-of-sample dataset. We hypothesize that future research may benefit by adding multimodal data to exploit advantages of more complex models.