Stable Cox regression for survival analysis under distribution shifts

Abstract

Survival analysis aims to estimate the impact of covariates on the expected time until an event occurs, which is broadly utilized in disciplines such as life sciences and healthcare, substantially influencing decision-making and improving survival outcomes. Existing methods, usually assuming similar training and testing distributions, nevertheless face challenges with real-world varying data sources, creating unpredictable shifts that undermine their reliability. This urgently necessitates that survival analysis methods should utilize stable features across diverse cohorts for predictions, rather than relying on spurious correlations. To this end, we propose a stable Cox model with theoretical guarantees to identify stable variables, which jointly optimizes an independence-driven sample reweighting module and a weighted Cox regression model. Through extensive evaluation on simulated and real-world omics and clinical data, stable Cox not only shows strong generalization ability across diverse independent test sets but also stratifies the subtype of patients significantly with the identified biomarker panels. Survival prediction models used in healthcare usually assume that training and test data share a similar distribution, which is not true in real-world settings. Cui and colleagues develop a stable Cox regression model that can identify stable variables for predicting survival outcomes under distribution shifts.