Time-varying effect in older patients with early-stage breast cancer: a model considering the competing risks based on a time scale

Abstract

BackgroundPatients with early-stage breast cancer may have a higher risk of dying from other diseases, making a competing risks model more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors of breast cancer may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor.MethodsTo address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale.ResultsA simulation validated the accuracy of the coefficient estimates in the proposed regression. Applying this model to an older early-stage breast cancer cohort, it was found that 1) the protective effects of positive estrogen receptor and chemotherapy decreased over time; 2) the protective effect of breast-conserving surgery increased over time; and 3) the deleterious effects of stage T2, stage N2, and histologic grade II cancer increased over time. Moreover, from the view of prediction, the mean C-index in external validation reached 0.78.ConclusionDynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist.