Heijnsdijk EAM, et al. - As in cancer screening trials, all-cause mortality has been suggested as an end-point in order to avoid biases in attributing the cause of death, researchers sought to determine the sample size and follow-up that may assist in finding a significant reduction in all-cause mortality. Performing a literature review, previous studies that modeled the effect of screening on all-cause mortality were identified. To simulate breast cancer, lung cancer, and colorectal cancer screening trials, they used microsimulation modeling. Cancer-specific deaths, all-cause deaths, and life-years gained per year of follow-up were the model outputs. The analysis supports the capability of cancer screening trials in illustrating a significant reduction in all-cause mortality due to screening, but these require very large sample sizes. Depending on the cancer, each arm requires 40,000-600,000 participants to describe a significant reduction. Detection of the decrease in all-cause mortality can only be done between specific years of follow-up, more limited than the timeframe to identify a decline in cancer-specific mortality.