Using pseudo-observations for estimation in relative survival

A common goal in the analysis of the long-term survival related to a specific disease is to estimate a measure that is comparable between populations with different general population mortality. When cause of death is unavailable or unreliable, as for example in cancer registry studies, relative survival methodology is used-in addition to the mortality data of the patients, we use the data on the mortality of the general population. In this article, we focus on the marginal relative survival measure that summarizes the information about the disease-specific hazard. Under additional assumptions about latent times to death of each cause, this measure equals net survival. We propose a new approach to estimation based on pseudo-observations and derive two estimators of its variance. The properties of the new approach are assessed both theoretically and with simulations, showing practically no bias and a close to nominal coverage of the confidence intervals with the precise formula for the variance. The approximate formula for the variance has sufficiently good performance in large samples where the precise formula calculation becomes computationally intensive. Using bladder cancer data and simulations, we show that the behavior of the new approach is very close to that of the Pohar Perme estimator but has the important advantage of a simpler formula that does not require numerical integration and therefore lends itself more naturally to further extensions.