Non-parametric estimation of net survival under dependence between death causes

Abstract: Relative survival methodology deals with a competing risks survival model where the cause of death is unknown. This lack of information occurs regularly in population-based cancer studies. Non-parametric estimation of the net survival is possible through the Pohar Perme estimator. Derived similarly to Kaplan-Meier, it nevertheless relies on an untestable independence assumption. We propose here to relax this assumption and provide a generalized non-parametric estimator that works for other dependence structures, by leveraging the underlying stochastic processes and martingales. We formally derive asymptotics of this estimator, providing variance estimation and log-rank-type tests. Our approach provides a new perspective on the Pohar Perme estimator and the acceptability of the underlying independence assumption. We highlight the impact of this dependence structure assumption on simulation studies, and illustrate them through an application on registry data relative to colorectal cancer, before discussing potential extensions of our methodology.