ABSTRACT Cancer prevention is recognized as a key strategy for reducing disease incidence, mortality, and the overall burden on individuals and society. However, determining when to begin preventive interventions presents a significant challenge: starting too early may lead to more interventions and increased lifetime burdens due to repeated administrations, while delaying may miss opportunities to prevent cancer. Evidence‐based recommendations require a benefit‐burden analysis that weighs life‐years gained against the burden of interventions. With the growing availability of large‐scale observational data, there is now an opportunity to empirically evaluate these trade‐offs. In this paper, we propose a causal framework for assessing the benefit and burden of cancer prevention, using an illness‐death model with semi‐competing risks. Extensive simulations demonstrate that the proposed estimators are unbiased, with robust inference across realistic scenarios. We apply this approach to a benefit‐burden analysis of the preventive screening for colorectal cancer, utilizing data from the large‐scale Women's Health Initiative. Our findings suggest that initiating screening at age 50 years achieves the highest life‐year gains with an acceptable incremental burden‐to‐benefit ratio compared to no screening, contributing valuable real‐world evidence to the field of preventive cancer interventions.
Xiong et al. (Sun,) studied this question.