Estimating the loss of lifetime function using flexible parametric relative survival models

Abstract Background Within cancer care, dynamic evaluations of the loss in expectation of life provides useful information to patients as well as physicians. The loss of lifetime function yields the conditional loss in expectation of life given survival up to a specific time point. Due to the inevitable censoring in time-to-event data, loss of lifetime estimation requires extrapolation of both the patient and general population survival function. In this context, the accuracy of different extrapolation approaches has not previously been evaluated. Methods The loss of lifetime function was computed by decomposing the all-cause survival function using the relative and general population survival function. To allow extrapolation, the relative survival function was fitted using existing parametric relative survival models. In addition, we introduced a novel mixture cure model suitable for extrapolation. The accuracy of the estimated loss of lifetime function using various extrapolation approaches was assessed in a simulation study and by data from the Danish Cancer Registry where complete follow-up was available. In addition, we illustrated the proposed methodology by analyzing recent data from the Danish Lymphoma Registry. Results No uniformly superior extrapolation method was found, but flexible parametric mixture cure models and flexible parametric relative survival models seemed to be suitable in various scenarios. Conclusion Using extrapolation to estimate the loss of lifetime function requires careful consideration of the relative survival function outside the available follow-up period. We propose extensive sensitivity analyses when estimating the loss of lifetime function.