A Stochastic Model for Calibrating the Survival Benefit of Screen-Detected Cancers

Comparison of the survival of clinically detected and screen-detected cancer cases from either population-based service screening programs or opportunistic screening is often distorted by both lead-time and length biases. Both are correlated with each other and are also affected by measurement errors and tumor attributes such as regional lymph node spread. We propose a general stochastic approach to calibrate the survival benefit of screen-detected cancers related to both biases, measurement errors, and tumor attributes. We apply our proposed method to breast cancer screening data from one arm of the Swedish Two-County trial in the trial period together with the subsequent service screening for the same cohort. When there is no calibration, the results—assuming a constant (exponentially distributed) post-lead-time hazard rate (i.e., a homogeneous stochastic process)—show a 57% reduction in breast cancer death over 25 years. After correction, the reduction was 30%, with approximately 12% of the overestimation being due to lead-time bias and 15% due to length bias. The additional impacts of measurement errors (sensitivity and specificity) depend on the type of the proposed model and follow-up time. The corresponding analysis when the Weibull distribution was applied—relaxing the assumption of a constant hazard rate—yielded similar findings and lacked statistical significance compared with the exponential model. The proposed calibration approach allows the benefit of a service cancer screening program to be fairly evaluated. This article has supplementary materials online.