Optimal treatment regimes in the presence of a cure fraction

Despite the widespread use of time-to-event data in precision medicine, existing research has often neglected the presence of the cure fraction, assuming that all individuals will inevitably experience the event of interest. When a cure fraction is present, the cure rate and survival time of uncured patients should be considered in estimating the optimal individualized treatment regimes. In this study, we propose direct methods for estimating the optimal individualized treatment regimes that either maximize the cure rate or mean survival time of uncured patients. Additionally, we propose two optimal individualized treatment regimes that balance the tradeoff between the cure rate and mean survival time of uncured patients based on a constrained estimation framework for a more comprehensive assessment of individualized treatment regimes. This framework allows us to estimate the optimal individualized treatment regime that maximizes the population's cure rate without significantly compromising the mean survival time of those who remain uncured or maximizes the mean survival time of uncured patients while having the cure rate controlled at a desired level. The exterior-point algorithm is adopted to expedite the resolution of the constrained optimization problem and statistical validity is rigorously established. Furthermore, the advantages of the proposed methods are demonstrated via simulations and analysis of esophageal cancer data.